conclusion for biology assignment

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Conclusions

Writing a Good Conclusion

The Conclusion is where you make it clear to the lab instructor what you learned in the lab experience. Since the purpose of the lab is to learn something about science, take the time to write a Conclusion that convinces the lab instructor of what you have learned.

Step 1: Restate your hypothesis.

Step 2 : Write one or more paragraphs that completely summarizes what you have learned from each part of the lab about the scientific concept of the lab from doing the lab. Back up your statement with supporting details (data) from your lab experience.

Step 3: Make sure that you interpret all of your data (Explain what your data means).

Additional Tips:

·         Strive for logic and precision and avoid ambiguity, especially with pronouns and sequences

·         Keep your writing impersonal; avoid the use of the first person (i.e. I or we)

·         Use the past tense and be consistent within the report note: “data” is plural and “datum” is singular; species is singular and plural

·         Italicize all scientific names (genus and species)

·         Use the metric system of measurement and abbreviate measurements without periods (i.e. cm  kg)

·         Spell out all numbers beginning sentences or less than 10 (i.e. “two explanations of six factors”).

·         Write numbers as numerals when greater than ten (i.e. 156) or associated with measurements (i.e. 6 mm or 2 g)

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• Science Writing

How to Write a Good Lab Conclusion in Science

Last Updated: June 18, 2024 Fact Checked

This article was co-authored by Bess Ruff, MA . Bess Ruff is a Geography PhD student at Florida State University. She received her MA in Environmental Science and Management from the University of California, Santa Barbara in 2016. She has conducted survey work for marine spatial planning projects in the Caribbean and provided research support as a graduate fellow for the Sustainable Fisheries Group. There are 11 references cited in this article, which can be found at the bottom of the page. This article has been fact-checked, ensuring the accuracy of any cited facts and confirming the authority of its sources. This article has been viewed 1,766,398 times.

A lab report describes an entire experiment from start to finish, outlining the procedures, reporting results, and analyzing data. The report is used to demonstrate what has been learned, and it will provide a way for other people to see your process for the experiment and understand how you arrived at your conclusions. The conclusion is an integral part of the report; this is the section that reiterates the experiment’s main findings and gives the reader an overview of the lab trial. Writing a solid conclusion to your lab report will demonstrate that you’ve effectively learned the objectives of your assignment.

Outlining Your Conclusion

• Restate : Restate the lab experiment by describing the assignment.
• Explain : Explain the purpose of the lab experiment. What were you trying to figure out or discover? Talk briefly about the procedure you followed to complete the lab.
• Results : Explain your results. Confirm whether or not your hypothesis was supported by the results.
• Uncertainties : Account for uncertainties and errors. Explain, for example, if there were other circumstances beyond your control that might have impacted the experiment’s results.
• New : Discuss new questions or discoveries that emerged from the experiment.

• Your assignment may also have specific questions that need to be answered. Make sure you answer these fully and coherently in your conclusion.

Discussing the Experiment and Hypothesis

• If you tried the experiment more than once, describe the reasons for doing so. Discuss changes that you made in your procedures.
• Brainstorm ways to explain your results in more depth. Go back through your lab notes, paying particular attention to the results you observed. [3] X Trustworthy Source University of North Carolina Writing Center UNC's on-campus and online instructional service that provides assistance to students, faculty, and others during the writing process Go to source

• Start this section with wording such as, “The results showed that…”
• You don’t need to give the raw data here. Just summarize the main points, calculate averages, or give a range of data to give an overall picture to the reader.
• Make sure to explain whether or not any statistical analyses were significant, and to what degree, such as 1%, 5%, or 10%.

• Use simple language such as, “The results supported the hypothesis,” or “The results did not support the hypothesis.”

Demonstrating What You Have Learned

• If it’s not clear in your conclusion what you learned from the lab, start off by writing, “In this lab, I learned…” This will give the reader a heads up that you will be describing exactly what you learned.
• Add details about what you learned and how you learned it. Adding dimension to your learning outcomes will convince your reader that you did, in fact, learn from the lab. Give specifics about how you learned that molecules will act in a particular environment, for example.
• Describe how what you learned in the lab could be applied to a future experiment.

• On a new line, write the question in italics. On the next line, write the answer to the question in regular text.

• If your experiment did not achieve the objectives, explain or speculate why not.

Wrapping Up Your Conclusion

• If your experiment raised questions that your collected data can’t answer, discuss this here.

• Describe what is new or innovative about your research.
• This can often set you apart from your classmates, many of whom will just write up the barest of discussion and conclusion.

Finalizing Your Lab Report

Community Q&A

• Ensure the language used is straightforward with specific details. Try not to drift off topic. Thanks Helpful 1 Not Helpful 0
• Once again, avoid using personal pronouns (I, myself, we, our group) in a lab report. The first-person point-of-view is often seen as subjective, whereas science is based on objectivity. Thanks Helpful 1 Not Helpful 0
• If you include figures or tables in your conclusion, be sure to include a brief caption or label so that the reader knows what the figures refer to. Also, discuss the figures briefly in the text of your report. Thanks Helpful 1 Not Helpful 0

• Take care with writing your lab report when working in a team setting. While the lab experiment may be a collaborative effort, your lab report is your own work. If you copy sections from someone else’s report, this will be considered plagiarism. Thanks Helpful 4 Not Helpful 0

You Might Also Like

• ↑ https://phoenixcollege.libguides.com/LabReportWriting/introduction
• ↑ https://www.education.vic.gov.au/school/teachers/teachingresources/discipline/english/literacy/Pages/puttingittogether.aspx
• ↑ https://writingcenter.unc.edu/tips-and-tools/brainstorming/
• ↑ https://advice.writing.utoronto.ca/types-of-writing/lab-report/
• ↑ http://www.socialresearchmethods.net/kb/hypothes.php
• ↑ https://libguides.usc.edu/writingguide/conclusion
• ↑ https://libguides.usc.edu/writingguide/introduction/researchproblem
• ↑ http://writingcenter.unc.edu/handouts/scientific-reports/
• ↑ https://phoenixcollege.libguides.com/LabReportWriting/labreportstyle
• ↑ https://writingcenter.unc.edu/tips-and-tools/editing-and-proofreading/

About This Article

To write a good lab conclusion in science, start with restating the lab experiment by describing the assignment. Next, explain what you were trying to discover or figure out by doing the experiment. Then, list your results and explain how they confirmed or did not confirm your hypothesis. Additionally, include any uncertainties, such as circumstances beyond your control that may have impacted the results. Finally, discuss any new questions or discoveries that emerged from the experiment. For more advice, including how to wrap up your lab report with a final statement, keep reading. Did this summary help you? Yes No

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BIOL/ESCI 304 - Ecology

Writing lab reports.

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This page provides guidelines that you will use to write your lab reports for the pollination lab, competition in ants and allelopathy in plants. You will apply many of these guidelines (use of citations, references, summarizing data, discussing conclusions) in other writing assignments.

All research papers in the field of biology follow the same basic format. There are almost always five sections: An Introduction, a Materials and Methods, a Results, a Discussion, and a Literature Cited section. Your lab report is a scientific paper and will follow this format.

Additional and more detailed information is also found in A Short Guide to Writing About Biology by Pachenek. Page numbers refer to specific pages in the 9th edition of the book, which provides additional information that you may need.

Species Name and Taxa Format (p. 11)

First mention in introduction: Give both the species common and scientific names (e.g., potato aphids ( Macrosiphum euphorbiae )).

After first mention: You can refer to your species by: its common name or an abbreviated scientific name (e.g., potato aphid or M. euphoribiae ).

Additional tips: Common names are never capitalized unless it is a proper name. Scientific names above the species level (genus, order, family) are always capitalized. In the scientific name, species name is NOT capitalized, genus is capitalized (see page 11 in a Short Guide ).

Materials and Methods (p. 152-157)

Overview: In this section you will describe the procedure you used to gather data. (1) You will provide information on the study area, how much/many samples were gathered, and how samples were gathered; (2) a concise description of the procedures and rationale used to gather the data (including a description of sample size and how data was gathered) — for both experiments; and (3) a concise description of the statistical analyses that were used to analyze the data.

Writing style example: "We gathered 4.82 g of boxelder tree leaves from the University of Michigan-Dearborn campus natural area and prepared a leaf extract solution following the procedures outlined in Reibesell et al. (2001).

To test if boxelder inhibited seed germination, we sterilized 75 radish ( Raphanus sativus ) seeds with 10% bleach solution, etc."

NOTE: It is appropriate to cite the lab manual in instances where you did not alter the directions from the lab manual at all. The key to a good materials and methods section is concise writing and making good decisions about the level of detail to include.

NOTE: You will want to describe your data analysis (p. 155), but you do NOT need to explicitly state a null hypothesis. Your null hypothesis is implied.

Results (p. 158-188)

Overview: This section has two parts —

(1) You will verbally summarize the data that you collected and verbally summarize your statistics. Be very careful not to interpret your results, just report them. Also, be sure to report your data and statistics (see below). You will reference your table and/or figures in this section (see below).

(2) You will also display your data in either a figure or a tabular format (whichever is appropriate for your data). Tables and figures are visual summaries of your data and should complement your verbal description. Tables and figures should be properly referenced in the narrative that summarizes your data. Tables should have a table caption above the table. Figures should have a figure legend below the figure. (See a Short Guide for what information should not be in a figure legend or table caption.)

Writing style example: "Significantly more rye seeds germinated in the control treatment (n = 48) than in both the strong and weak extracts (n = 12, 13 respectively; Chi-square = 10.28, P-value = 0.001; Table 1)."

NOTE: Do NOT write this section without reading the accompanying pages in a Short Guide . Sentence phrasing is very important when writing about results and statistics. It helps with clarity and helps avoid interpretation. Reading the Short Guide will help you understand how to properly phrase your sentences.

NOTE: This is where students make the most stylistic mistakes. There are specific guidelines for presenting numbers, statistics, figures, etc.

NOTE: Tables and figures should be sequentially numbered according to the order they are discussed in the text of the results section. The best way to ensure they are numbered correctly is to number them AFTER you have written the results section. Then you can go back and number each in the order it was referenced in the text portion of your results.

Discussion (p. 188-195)

Start this section by stating your conclusion. Be sure to state your conclusion in reference to your original hypothesis (expectation). Then discuss what this means — this is where you will interpret your data. In this section, you will discuss and interpret your data. You will discuss the "why" of the pattern of your data. You will need to include a few sentences that put your data in the context of other literature and findings, and relate your results to the biological principles you stated you were testing in the Introduction section. In these sentences, you will reference other literature. It can be the same literature that you mentioned in your Introduction, but it does not have to be. In this section, you will be answering "why" questions about the data and interpreting the data. You should discuss whether you accepted or rejected your original hypothesis based on your data. Discuss your opinion of your results and what your results mean. Organizationally, it makes sense to discuss your results in the order in which they were presented. Do not reference your tables or figures specifically. You have already done that. Speculate on WHY you think your data came out as they did. In this section, do not be afraid of wild speculations if they are within the realm of biological possibility. Do not state whether the study was bad or good, or whether the results were bad or good. Making subjective, judgmental statements about data is inappropriate for scientific writing. In other words, avoid bias! If the study had many faults, or if the data turned out so that no biological principles could be deduced from the results, then you would want to discuss ways in which the study could have been improved. You may want to discuss this even if you had a great study. A good way to end a discussion section is as follows — "In conclusion..." and briefly summarize the results and conclusions of the experiment.

Example: "As expected, different numbers of seeds germinated in each of the three treatments. Significantly more seeds germinated in the control treatment than in the strong extract. This indicates that boxelder leaves may have allelopathic chemicals that inhibit seed germination etc."

NOTE: Be careful not to overstate your findings. Address just your study.

NOTE: You should not include any actual results in this section. DO not restate your statistics; do not give specific numbers; do not reference tables or figures.

Introduction (p. 195-201)

You will include two essential pieces of information in this section.

(1) Introduce the topic on which you gathered data and explain the phenomenon you studied. Explain why the study is important. Include a problem statement and/or question.

(2) You must also state the scientific hypothesis you tested after leading up to it with your explanation of the topic. State your prediction or expectation of your outcome.

Example: "Allelopathy is a chemical competition phenomenon produced in plants that influences the growth of other organisms. The study of allelopathy is important in agriculture because positive results can be used as a natural deterrent of invasive species. This experiment was designed to test whether water-soluble American elm tree ( Ulmus americana )...

NOTE: All relevant text should be cited! See page 203 for how to properly cite sources.

The title should be brief, but descriptive of the study and include important, relevant, and specific information. The title should be written in sentence case. The title should include your species name and the species should be presented properly. The title should be centered at the top of the page.

NOTE: Common name and scientific name should be presented in the title (see above and Introduction for examples of properly presenting species name).

NOTE: You may want to write this last because that is when you will have the most complete understanding of your report.

Literature Cited (Chapter 5)

You must include AT LEAST two references in your laboratory report. (The lab manual and textbook do not count.)

References are often included in both the Introduction and Discussion sections to bolster speculation or comment.

NOTE: In the Literature Cited section, you will cite your literature following the guidelines on the How to Cite in Ecology Style page of this subject guide. Citing scientific literature often follows different guidelines than MLA, and different journals have different rules. Because this is ecology, we are following the guidelines for the Journal of Ecology .

Format to use for the Lab Manual:

Riebesell, J, Taquia, S. and Leach, K. 2000. Allelopathy and Secondary Compounds. University of Michigan Dearborn Ecology Lab Manual.

Web citations are not permitted for the lab report. They are not subjected to peer review (review by other scientists) as are books and journal articles. Therefore, too many are unsubstantiated, and they are not accepted.

Additional Requirements for Your Lab

• The report must look good. Take care in your presentation of all components of your report.
• You do not need a cover page or report cover.
• The report must be single spaced in 12-point font with 0.75" - 1.0" margins on all sides.
• The report cannot be over 3-4 pages. This is more than sufficient for this lab report.
• Do not include a separate title page.
• Do not use second person — e.g., do not say something like "As you can see from Figure 1..."
• Use past tense, especially in the Materials and Methods, and Results sections. The lab has already been completed.
• Do not quote from citations. Instead, paraphrase the ideas expressed by the author(s).
• Do not use contractions; i.e., don't use contractions like I just did!
• Superscripts and subscripts must be printed properly; e.g., H 2 O, not H20.
• Any calculated values should be rounded to one or two decimal places.
• The word "data" is the plural form of "datum". Learn to use the word "data" as a plural word.
• Do not turn in your report in any type of folder or binder. Staple the pages together.
• If beginning a sentence with a number, write out the number. Refer to zero and one with words not numbers (0 or 1). Numbers smaller than zero should be preceded with a zero and a decimal (e.g., 0.5).
• Numbers one through ten should be written out.
• Scientific names should be properly presented.
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• How to conclude an essay | Interactive example

How to Conclude an Essay | Interactive Example

Published on January 24, 2019 by Shona McCombes . Revised on July 23, 2023.

The conclusion is the final paragraph of your essay . A strong conclusion aims to:

• Tie together the essay’s main points
• Show why your argument matters
• Leave the reader with a strong impression

Your conclusion should give a sense of closure and completion to your argument, but also show what new questions or possibilities it has opened up.

This conclusion is taken from our annotated essay example , which discusses the history of the Braille system. Hover over each part to see why it’s effective.

Braille paved the way for dramatic cultural changes in the way blind people were treated and the opportunities available to them. Louis Braille’s innovation was to reimagine existing reading systems from a blind perspective, and the success of this invention required sighted teachers to adapt to their students’ reality instead of the other way around. In this sense, Braille helped drive broader social changes in the status of blindness. New accessibility tools provide practical advantages to those who need them, but they can also change the perspectives and attitudes of those who do not.

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Table of contents

Step 1: return to your thesis, step 2: review your main points, step 3: show why it matters, what shouldn’t go in the conclusion, more examples of essay conclusions, other interesting articles, frequently asked questions about writing an essay conclusion.

To begin your conclusion, signal that the essay is coming to an end by returning to your overall argument.

Don’t just repeat your thesis statement —instead, try to rephrase your argument in a way that shows how it has been developed since the introduction.

Prevent plagiarism. Run a free check.

Next, remind the reader of the main points that you used to support your argument.

Avoid simply summarizing each paragraph or repeating each point in order; try to bring your points together in a way that makes the connections between them clear. The conclusion is your final chance to show how all the paragraphs of your essay add up to a coherent whole.

To wrap up your conclusion, zoom out to a broader view of the topic and consider the implications of your argument. For example:

• Does it contribute a new understanding of your topic?
• Does it raise new questions for future study?
• Does it lead to practical suggestions or predictions?
• Can it be applied to different contexts?
• Can it be connected to a broader debate or theme?

Whatever your essay is about, the conclusion should aim to emphasize the significance of your argument, whether that’s within your academic subject or in the wider world.

Try to end with a strong, decisive sentence, leaving the reader with a lingering sense of interest in your topic.

The easiest way to improve your conclusion is to eliminate these common mistakes.

Don’t include new evidence

Any evidence or analysis that is essential to supporting your thesis statement should appear in the main body of the essay.

The conclusion might include minor pieces of new information—for example, a sentence or two discussing broader implications, or a quotation that nicely summarizes your central point. But it shouldn’t introduce any major new sources or ideas that need further explanation to understand.

Don’t use “concluding phrases”

Avoid using obvious stock phrases to tell the reader what you’re doing:

• “In conclusion…”
• “To sum up…”

These phrases aren’t forbidden, but they can make your writing sound weak. By returning to your main argument, it will quickly become clear that you are concluding the essay—you shouldn’t have to spell it out.

Don’t undermine your argument

Avoid using apologetic phrases that sound uncertain or confused:

• “This is just one approach among many.”
• “There are good arguments on both sides of this issue.”
• “There is no clear answer to this problem.”

Even if your essay has explored different points of view, your own position should be clear. There may be many possible approaches to the topic, but you want to leave the reader convinced that yours is the best one!

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• Argumentative
• Literary analysis

This conclusion is taken from an argumentative essay about the internet’s impact on education. It acknowledges the opposing arguments while taking a clear, decisive position.

The internet has had a major positive impact on the world of education; occasional pitfalls aside, its value is evident in numerous applications. The future of teaching lies in the possibilities the internet opens up for communication, research, and interactivity. As the popularity of distance learning shows, students value the flexibility and accessibility offered by digital education, and educators should fully embrace these advantages. The internet’s dangers, real and imaginary, have been documented exhaustively by skeptics, but the internet is here to stay; it is time to focus seriously on its potential for good.

This conclusion is taken from a short expository essay that explains the invention of the printing press and its effects on European society. It focuses on giving a clear, concise overview of what was covered in the essay.

The invention of the printing press was important not only in terms of its immediate cultural and economic effects, but also in terms of its major impact on politics and religion across Europe. In the century following the invention of the printing press, the relatively stationary intellectual atmosphere of the Middle Ages gave way to the social upheavals of the Reformation and the Renaissance. A single technological innovation had contributed to the total reshaping of the continent.

This conclusion is taken from a literary analysis essay about Mary Shelley’s Frankenstein . It summarizes what the essay’s analysis achieved and emphasizes its originality.

By tracing the depiction of Frankenstein through the novel’s three volumes, I have demonstrated how the narrative structure shifts our perception of the character. While the Frankenstein of the first volume is depicted as having innocent intentions, the second and third volumes—first in the creature’s accusatory voice, and then in his own voice—increasingly undermine him, causing him to appear alternately ridiculous and vindictive. Far from the one-dimensional villain he is often taken to be, the character of Frankenstein is compelling because of the dynamic narrative frame in which he is placed. In this frame, Frankenstein’s narrative self-presentation responds to the images of him we see from others’ perspectives. This conclusion sheds new light on the novel, foregrounding Shelley’s unique layering of narrative perspectives and its importance for the depiction of character.

If you want to know more about AI tools , college essays , or fallacies make sure to check out some of our other articles with explanations and examples or go directly to our tools!

• Ad hominem fallacy
• Post hoc fallacy
• Appeal to authority fallacy
• False cause fallacy
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Your essay’s conclusion should contain:

• A rephrased version of your overall thesis
• A brief review of the key points you made in the main body
• An indication of why your argument matters

The conclusion may also reflect on the broader implications of your argument, showing how your ideas could applied to other contexts or debates.

For a stronger conclusion paragraph, avoid including:

• Important evidence or analysis that wasn’t mentioned in the main body
• Generic concluding phrases (e.g. “In conclusion…”)
• Weak statements that undermine your argument (e.g. “There are good points on both sides of this issue.”)

Your conclusion should leave the reader with a strong, decisive impression of your work.

The conclusion paragraph of an essay is usually shorter than the introduction . As a rule, it shouldn’t take up more than 10–15% of the text.

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the “Cite this Scribbr article” button to automatically add the citation to our free Citation Generator.

McCombes, S. (2023, July 23). How to Conclude an Essay | Interactive Example. Scribbr. Retrieved June 18, 2024, from https://www.scribbr.com/academic-essay/conclusion/

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How to Conclude an Assignment to Make It the Cherry on Top

Table of Contents

What Is a Conclusion?

Why are conclusions written, how to write a conclusion for an assignment, useful strategies for conclusion writing, typical words to start a conclusion, a conclusion example for assignment, now, it’s time for this article’s conclusion….

A conclusion is a summary of the whole assignment. It should restate the thesis, summarize key ideas presented in the assignment, and leave the reader with a final idea about the topic in general to ponder further! It is the most logical way to end an assignment. Conclusion writing is not so difficult!

The purpose of a conclusion is to link the thesis statement (written in the introduction) with main ideas or points (made in the main body) and provide an overall message. A conclusion provides closure and is expected in most academic related writing, including assignments, research papers, and essays.

To write an assignment conclusion, follow the 7 simple steps below!

• Start a conclusion paragraph by indenting the first line or leaving a blank line in between the last main body paragraph and the conclusion.
• Use a suitable starting word or phrase to indicate the assignment is drawing to a close, such as, ‘In summary’ or ‘With all this in mind’ (read on for further example starter words and phrases).
• Revisit your introduction to remind yourself of the thesis e.g., ‘The biggest contributor to global warming is animal agriculture’ . Then, either paraphrase or answer the thesis e.g., ‘In summary, animal agriculture is the main cause of global warming’ .
• Summarize the main point made by each paragraph in the assignment. So, if you have written 3 main body paragraphs, there should be 3 main points stated in the conclusion e.g., ‘ The animal agricultural sector causes extensive GHG emissions. As the world population grows, increasingly colossal areas of rainforest are being cleared for farmed animals, to keep up the demand for meat. Furthermore, seemingly unmeasurable amounts of animal wastes are polluting vast areas of land and water, thus ruining the biodiversity that helps to keep our planet’s GHG’s balanced’.
• Ensure you do not give the reader any new information. The conclusion is not the place for this.
• To end a paragraph, give your readers a closing sentence about the overall topic and try to encourage them to think further e.g., ‘If the world’s population continues to grow at its current rate and we do not make the shift towards a plant-based diet fast enough, we may reach a point whereby the damage to the ozone layer is beyond repair’ .
• Finally, end a conclusion, proof-read it! Do not skip this part! There is no point writing an amazing conclusion in assignment if readers cannot understand it or spot several spelling, punctuation, or grammatical errors!

• Bear in mind that a conclusion paragraph is written in reverse order to the introduction. The introduction will begin with a general topic, focus on specific aspects of it, and then state a thesis. A conclusion for an assignment will be the other way around (thesis, main points, topic in general).
• Remember, you are aiming to bring the reader’s mind back to the introduction and the key information given to them.
• Encourage the reader to consider the future implications of the information you have provided them. This could be a general, wide statement about the topic or a question relating to the general topic to give the reader an alternative perspective or encourage their on-going thinking, after they have finished reading! The final sentence could be a ‘call to action’, a warning, or a future prediction.

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It’s important for the reader to sense the assignment is ending. Here are some useful words and phrases that can help you achieve this, and transition well into the concluding paragraph of your assignment:

• Given the circumstances
• Now that one knows
• The logical conclusion appears to be
• To summarize
• Upon consideration of the facts discussed
• After the exploration of multiple professional viewpoints
• In view of this information
• Nevertheless
• When faced with the dilemma of
• Bearing all this in mind
• It seems clear that
• Given the evidence presented
• With all aspects considered

When writing a conclusion for an assignment, it can be easier to see an example:

Overall, owning a pet is a huge commitment that can span many years of one’s life. A pet will require regular feeding and day-to-day care. Many pets need large amounts of human interaction, attention, and affection which can be time-consuming. Furthermore, a pet may incur great costs by means of food, medical care and pet sitting (whenever the owner wants to go on vacation without the pet). The decision of whether to welcome a pet into your home must be considered in great depth, and at length, to prevent another potentially unwanted animal ending its life in an animal shelter. 

Ultimately, writing a concluding paragraph is simple when you refer to the introduction for the assignment , and the key points made in the main body. All the information you need is already there, but it just needs re-working to provide the reader with closure, and perhaps also get them thinking further about the points you have made!

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Tips on How to Write a Biology Essay: Learn from the Example of Jellyfish Essay

How to Write a Biology Essay

In this article, we will guide you on how to write a perfect biology essay from scratch. You’ll find various tips to help you excel in writing your essay and creating a paper worth the highest grades. We also prepared a jellyfish essay example for you, so it can be easier to enhance all the specifics and structure of this kind of paper.

What is Biology Essay

A biology essay is a student-written work where you present arguments and ideas about a particular biological topic. The essay on biology can take different forms like argumentative, cause-and-effect, descriptive, detailed analysis, or ‘how-to’ instruction, depending on the professor’s guidelines and writer’s preferences. 

A descriptive paper can explain a biological subject, while an argumentative one provides evidence to support a point of view. It’s up to you to choose which type is more suitable for the topic you’re writing about. The most common type is a cause-and-effect essay explaining an event’s reasons and consequences. 

How to Craft a Perfect Essay About Biology

Writing is an art form that requires time and effort. But if you prefer someone else to write the paper for you, you can just text the experts, ‘ do my homework for me ,’ and consider it done. 

Here is the step by step instruction to organize the process for desired results. 

Choose Your Biology Essay Topic

To get a good grade:

• make your paper informative and enjoyable by choosing a topic you wish to explore. 
• Use a brainstorming technique to generate 30-50 options for biology essay topics and research to create a shortlist. 
• Keep a notebook to jot down your ideas.

Choose a Question for Research

When writing a biology essay, use a scientific approach by selecting a research question related to your topic. Always avoid overly complex or apparent questions. You can also text our profs ‘ write my research paper ,’ and it can be done in a blink.

Create an Outline

Always have a clear plan when writing biology essays while starting a paper. Use a 5-paragraph structure with an outline to keep your main idea and arguments organized. Use any format that works best for you and adjust as needed. Discard any ideas that don’t fit your research question.

Use a Strong Thesis Statement

The introduction should end with a strong thesis statement synthesizing the overall essay, conveying the research question and your point of view. The paper is ineffective without a clear thesis, as readers may not understand your position.

Use Citation and References

Include a list of references in your academic papers, such as biology essays, to avoid plagiarism and provide data sources. Use the appropriate citation style, like APA or CSE, and consult a guide for requirements.

How to Structure a Biology Essay

Ensure your essay has an attention-grabbing introduction, a detailed body, and a solid conclusion with distinct sections. Use around seven paragraphs for the main body, adjusting as needed for the required word count.

Biology Essay Introduction

In the introduction of your essay about biology, showcase your expertise by providing a brief background of the topic and stating the essay’s objective. For a research paper, explain why the study is relevant. Make sure the reader understands the essence of your subject.

The body section of your essay on biology should focus on supporting and defending your thesis statement. To achieve this, make a list of essential points to cover and address each one step by step. Starting a new paragraph for each point ensures neatness and a continuous flow. 

In conclusion, restate your thesis statement and summarize supporting points to solidify your arguments. Avoid introducing new concepts, and leave a lasting impression on your instructor.

Jellyfish Essay - Example of a Biology Essay About a Fascinating Creature of the Ocean

Jellyfish, also known as jellies, are incredible creatures of the ocean. They’re members of the phylum Cnidaria, including corals and sea anemones. You can find jellyfish in every ocean around the globe, from the surface to the depths of the sea. 

Do you know what shape the jellyfish body has?! It’s one of their most unique features. Their bell-shaped body comprises a soft, jelly-like substance called mesoglea, found between two cellular layers. The outer layer of cells, the epidermis, is thin and flexible, while the inner layer, the gastrodermis, contains the jellyfish’s digestive system. At the bottom of the bell is the mouth, surrounded by tentacles armed with stinging cells called nematocysts. 

The jellyfish tentacles consist of venom-filled sacs, which can be potentially dangerous and life-threatening. Considering the severity of its sting, researchers have gathered information on how to treat it effectively. Use thick clothing, tweezers, sticks, or gloves to alleviate the sting. It’s crucial to avoid touching the sting with bare skin since the venom can cause severe harm. Always dispose of the tool used for removing the sting to prevent re-stinging. 

Jellyfish are creatures that feed on small fish and other tiny marine organisms. They capture their prey using the tentacles and bring it to their mouth. Once the food is inside the jellyfish, it’s broken down by digestive enzymes and absorbed into the gastrovascular cavity. 

An exciting thing about jelly is its life cycle. They go through several stages of development, starting as a tiny, free-swimming larva and then growing into a polyp. The polyp stage is stationary, and the jellyfish attaches itself to a surface using a sticky pad. During this stage, the jellyfish reproduces asexually, creating clones of itself. These clones then break off from the polyp and develop into the familiar bell-shaped body of the adult jellyfish. 

Jellyfish play an essential role in the ocean’s ecosystem too. They’re a food source for many marine creatures, including sea turtles and some fish species. They also help to control the population of tiny marine animals by feeding on them, and their waste products contribute to the nutrient cycle in the ocean.

However, jellyfish populations can sometimes explode and become a nuisance. This phenomenon mostly occurs when their natural predators are eliminated from the ecosystem or when water conditions, like temperature and salinity, are conducive for jellyfish growth. In cases where jellyfish populations reach excessive levels, they can clog fishing nets and interfere with other human activities in the ocean.

Jellyfish really are stunning creatures of the ocean. They’re diverse, with many different species, and are essential to the marine ecosystem. While they can sometimes become a nuisance, they’re vital to the ocean’s food web and nutrient cycle. Studying jellyfish can give us a greater understanding of the complex and interconnected systems that make up our oceans.

Practical Tips for Creating Perfect Academic Papers

Developing writing skills is crucial for your academic success regardless of your major. Check out these tips we provided for improving your writing. But if you aren't fond of writing, you can easily hand it to professionals by saying, ‘ do homework for me .’

Search for Samples or Examples

To improve your writing, analyze examples of well-written biology essays or research papers. Although not all online samples are perfect, they can still provide insights into what works and what doesn’t. However, avoid plagiarism and ensure your paper is original by presenting fresh ideas and a unique perspective. 

Read Whenever You Can

Develop your writing skills by reading widely and extensively. Look for biology papers in scientific journals, websites, or books. Don’t forget to take notes on interesting points that you can use in your papers later.

Practice Makes Perfect

Don’t expect to write a perfect paper on your first try, so take every opportunity to practice your writing. Find a mentor if needed and use online resources to learn from your mistakes and improve your skills.

Always Organize Your Writing Process

Organize your work process instead of waiting for inspiration by defining stages, scheduling time for each task, and eliminating distractions. Don’t wait for mood to write an essay about biology; use different strategies to overcome writer’s block.

Proofread and Get Other Feedback

It’s hard to assess your own work accurately. Seek feedback from peers or instructors to identify strengths and weaknesses to improve upon. Don’t wait for your professor’s feedback to know if your biology essay is good. 

Interesting Biology Essay Topics from Our Experts to Practice Your Writing

In this paragraph, we listed different biology essay topics from which you can choose your preferred one and practice writing to excel in your academic papers.

• A jellyfish - my favorite creature
• Facts about animal behavior
• Biodiversity conservation
• Chemical Ecology
• Impacts of air pollution
• Acid Rain’s impact on wildlife
• The greenhouse effect
• Causes of global warming
• Effects of climate change on nature
• Ways to avoid water pollution

These are interesting topics and also some of the most significant environmental problems. Choose the one you like and practice.

Final Thoughts

This article provides tips that will definitely make your writing process easier and more effective. Adjust these tips while writing your biology paper and structure it as we did in the jellyfish essay example. But if you still prefer a professional to do it for you, contact us by writing ‘ do my research paper ,’ and our experts will handle it.

Ryan Acton is an essay-writing expert with a Ph.D. in Sociology, specializing in sociological research and historical analysis. By partnering with EssayHub, he provides comprehensive support to students, helping them craft well-informed essays across a variety of topics.

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• How to Write Discussions and Conclusions

The discussion section contains the results and outcomes of a study. An effective discussion informs readers what can be learned from your experiment and provides context for the results.

What makes an effective discussion?

When you’re ready to write your discussion, you’ve already introduced the purpose of your study and provided an in-depth description of the methodology. The discussion informs readers about the larger implications of your study based on the results. Highlighting these implications while not overstating the findings can be challenging, especially when you’re submitting to a journal that selects articles based on novelty or potential impact. Regardless of what journal you are submitting to, the discussion section always serves the same purpose: concluding what your study results actually mean.

A successful discussion section puts your findings in context. It should include:

• the results of your research,
• a discussion of related research, and
• a comparison between your results and initial hypothesis.

Tip: Not all journals share the same naming conventions.

You can apply the advice in this article to the conclusion, results or discussion sections of your manuscript.

Our Early Career Researcher community tells us that the conclusion is often considered the most difficult aspect of a manuscript to write. To help, this guide provides questions to ask yourself, a basic structure to model your discussion off of and examples from published manuscripts. 

Questions to ask yourself:

• Was my hypothesis correct?
• If my hypothesis is partially correct or entirely different, what can be learned from the results? 
• How do the conclusions reshape or add onto the existing knowledge in the field? What does previous research say about the topic? 
• Why are the results important or relevant to your audience? Do they add further evidence to a scientific consensus or disprove prior studies? 
• How can future research build on these observations? What are the key experiments that must be done? 
• What is the “take-home” message you want your reader to leave with?

How to structure a discussion

Trying to fit a complete discussion into a single paragraph can add unnecessary stress to the writing process. If possible, you’ll want to give yourself two or three paragraphs to give the reader a comprehensive understanding of your study as a whole. Here’s one way to structure an effective discussion:

Writing Tips

While the above sections can help you brainstorm and structure your discussion, there are many common mistakes that writers revert to when having difficulties with their paper. Writing a discussion can be a delicate balance between summarizing your results, providing proper context for your research and avoiding introducing new information. Remember that your paper should be both confident and honest about the results! 

• Read the journal’s guidelines on the discussion and conclusion sections. If possible, learn about the guidelines before writing the discussion to ensure you’re writing to meet their expectations. 
• Begin with a clear statement of the principal findings. This will reinforce the main take-away for the reader and set up the rest of the discussion. 
• Explain why the outcomes of your study are important to the reader. Discuss the implications of your findings realistically based on previous literature, highlighting both the strengths and limitations of the research. 
• State whether the results prove or disprove your hypothesis. If your hypothesis was disproved, what might be the reasons? 
• Introduce new or expanded ways to think about the research question. Indicate what next steps can be taken to further pursue any unresolved questions. 
• If dealing with a contemporary or ongoing problem, such as climate change, discuss possible consequences if the problem is avoided. 
• Be concise. Adding unnecessary detail can distract from the main findings. 

Don’t

• Rewrite your abstract. Statements with “we investigated” or “we studied” generally do not belong in the discussion. 
• Include new arguments or evidence not previously discussed. Necessary information and evidence should be introduced in the main body of the paper. 
• Apologize. Even if your research contains significant limitations, don’t undermine your authority by including statements that doubt your methodology or execution. 
• Shy away from speaking on limitations or negative results. Including limitations and negative results will give readers a complete understanding of the presented research. Potential limitations include sources of potential bias, threats to internal or external validity, barriers to implementing an intervention and other issues inherent to the study design. 
• Overstate the importance of your findings. Making grand statements about how a study will fully resolve large questions can lead readers to doubt the success of the research. 

Snippets of Effective Discussions:

Consumer-based actions to reduce plastic pollution in rivers: A multi-criteria decision analysis approach

Identifying reliable indicators of fitness in polar bears

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• How to Report Statistics
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How to write Biology Assignment

• August 11, 2016
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Biology can be very challenging and is a vast subject, includes the study of life and living organism, evolution, and distribution, such as different species, plants, animals, insects, and algae. Biology is more of a practical rather than theoretically based assignments, as it is more related to practical research about the living organism’s cell, cell transformations, and other areas. Biology requires lots of dedication and discipline. When is comes to write a biology assignment, it is comprised of lots of research and writing. Students must have a sound knowledge of the subject and topic. Good writing skills can improve your work and help you earn good grades. There are some basic guidelines, to complete your biology assignment on time and efficiently.

  Be Precise and Credible For biology assignments, it is important to have accurate and reliable knowledge of research and facts. Make sure you know all the facts and the related theory of the topic of the assignment. Make notes of important components and points you need to be related to the assignment. Make a list of how to structure the information in each section. For more details, use good quality references such as specialised scientific books and journals. Scientists themselves write books and articles so reading them will help you in maintaining high standards in scientific literature. You can ask your tutor to refer you some good authors.

  Research originality The originality of the research is vital. Originality is the product of the researcher’s work and new ideas. Taking knowledge from someone else’s research and adding your new ideas to them also count as original, but only if the researcher can convince his/her new ideas. You can use few diagrams and figures to convey the information more accurately. Only the most pertinent information should be used to support your argument. Before paraphrasing material from the references, make sure that the sources are fully acknowledged, it will be helpful to seek the help of your lecturer in this, discuss it with other students before preparing your piece of work.

  Style and structure Using the proper style and structure is essential for writing an assignment. Make sure your work is easy to read and follow. To make the paper readable, use the proper fonts such as Times, Geneva, Bookman, etc. text should be double spaced from the lines above and below with 1-inch margins. Start each new section on the new page. Avoid mistakes like placing heading at the bottom of the page. Restrict each figure or table in a single page. Use paragraphs to separate important points. Indent first line of each and every paragraph. Use active voice to report well-accepted facts and passive voice to describe the results. Include figures that are necessary to present results. You can subdivide your work into the following sections:

  Title (Describing the content of the paper) The title should be at the center of the page. The title should not be italicized and underlined. Use informative titles that accompany the content and examples written in your assignment. For example, the organism used, the molecule studied, the treatment, the response measured, etc.

  Abstract (Summary of the paper) The summary is written, at the end of the article. Abstract include the logic behind the study, results, approach to the problems and critical questions or conclusions. You can keep it condensed by using words that serve more than one purpose, such as methods, type of analysis and the overall problem.

Introduction (Importance and problems discussed) The introduction should not exceed two pages. The purpose of the introduction is to enlighten the reader with the reason behind the work. Describe the importance and worth of the study, with the intention of defending it. Why this particular system was used and what are its advantages? State the specific objective or hypothesis.

Methods (Solution to the problems) To be particular, present methods under heading for specific procedures. Mention how procedures were done instead of how they were performed. Always use passive voice sentences. Methods are not a set of instructions. Leave all the explanatory background and information.

Results (Present your findings) The purpose of writing results is to perform and display your findings. Convert your analyzed data in the form of the table, figure or the text form. Describe the results of experiments and include observations, presented in the table, figure, if required, don’t discuss or report background information for your results. Text written should complement your figures and tables.

  Discussion (Interpretation of your results) This section is to support your conclusions, by using the evidence from your experiments. You can suggest future methods such as how the test can be modified to achieve another objective. Mention the work done by the particular individual or by yourself in the passive voice and principle and accepted facts in the active voice.

  Acknowledgement (Resources used) Acknowledgement is the last section of the assignment, listing all the references you cited in the text, with the corresponding references. The references cited should be given in the alphabetical listing.

If you feel muddled anywhere or need more information on your paper or topic, you can take online help for your assignments. Makemysssignments help students with their academic assignments.

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How To Write A Thesis Conclusion For Biological Life Science?

A thesis is the most integral part of a research, for it is the compilation of your years of hard work. It is a great learning process for the students for they understand how to analyze their work critically and compile it into a dissertation. Despite the task being a learning process, most people find it overwhelming considering the amount of labour involved. A thesis entails many chapters and writing the conclusion is the most significant task of all. This article gives you tips on how to write your conclusion chapter.

Why Do We Need A Conclusion Chapter?

Most people view introduction and conclusion as the insignificant parts of a dissertation. But, trust me when I say they are the two chapters that readers remember the most. So, make it interesting for your readers. A conclusion is more or less like a climax scene in a movie. It helps your reader determine their level of satisfaction with your work and gives them an idea of whether or not your dissertation has accomplished its purpose. Most readers will not read the entire thesis; instead, try to note down important points from your conclusion for it entails the summary of every chapter of your thesis. So, make it worthwhile for them.  

Things To Remember When You Write A Conclusion:

The task of writing a conclusion is somewhat laborious, so most people run out of words towards the end of a thesis and are intended to finish the thesis with a sub-par conclusion somehow.

• Since it is your study, take full liberty to be subjective and put down your thoughts about the study. But, make sure you don’t force your opinion on your readers.
• Accept the fact that every thesis has limitations and do not shy away from adding it in your thesis.
• The primary purpose of a study is to provide answers to every question raised, so make sure you do not leave your readers hanging or give them neutral responses.
• In a bid to make your conclusion interesting, do not go off the track or take a new path, altogether. Just stick to summarising your content.
• Be careful with grammar and tenses. Go for Present Perfect or Simple Past, and avoid spelling mistakes. 
• One of the common mistakes that most researchers do is ruining their conclusion by repeating content. Use your conclusion chapter only to summarise.
• A reader often finds a thesis too dull or formal, for it is filled with jargons. So, channel your inner writer and make your conclusion as creative and interactive as possible, so that the readers can find some relation with it. 
• Don’t go for the clichés for it makes your thesis dull or blunt. Make it as natural and professional as you can.
• Your conclusion should contain the result of your thesis, so back your result with logical explanations and do not pick sides.
• Never apologize or use sentences in your thesis, suggesting you’re not an expert or that people can view your findings as a suggestion for it belittles your work.

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Review Essays for the Biological sciences

A review essay for the biological sciences serves to discuss and synthesize key findings on a particular subject. Review papers are helpful to the writer and their colleagues in gaining critical awareness in specialized fields that may or may not be their own.

This guide explains what a review essay is and identifies several approaches to writing a review essay. Although much of the information is geared directly to the biological sciences, it is generally applicable to review essays in all fields.

What is a Review Essay?

A review essay is a synthesis of primary sources (mainly research papers presented in academic journals) on a given topic. A biological review essay demonstrates that the writer has thorough understanding of the literature and can formulate a useful analysis. While no new research is presented by the writer, the field benefits from the review by recieving a new perspective. There are several approaches one may take when writing a biological review:

A State of the art review

A state of the art review considers mainly the most current research in a given area. The review may offer new perspectives on an issue or point out an area in need of further research.

A Historical review

A historical review is a survey of the development of a particular field of study. It may examine the early stages of the field, key findings to present, key theoretical models and their evolution, etc.

A Comparison of perspectives review

A comparison of perspectives review contrasts various ways of looking at a certain topic. If in fact there is a debate over some process or idea, a comparison of perspectives review may illustrate the research that supports both sides. A comparison of perspectives review may introduce a new perspective by way of comparing it to another.

A Synthesis of two fields review

Many times researchers in different fields may be working on similar problems. A synthesis of two fields review provides insights into a given topic based on a review of the literature from two or more disciplines.

A Theoretical model building review

A theoretical model building review examines the literature within a given area with the intention of developing new theoretical assumptions.

Key Considerations for Writing a Biological Review Essay

This guide will inform you of certain things not to miss when writing a review essay. It will also give you some information about using and documenting your sources.

Keep your focus narrow.

When writing a review essay it is important to keep the scope of the topic narrow enough so that you can discuss it thoroughly. For example a topic such as air quality in factories could be narrowed significantly to something like carbon dioxide levels in auto manufacturing plants .

A good way to narrow your focus is to start with a broad topic that is of some interest to you, then read some of the literature in the field. Look for a thread of the discussion that points to a more specific topic.

Analyze, synthesize, and interpret.

A review essay is not a pure summary of the information you read for your review. You are required to analyze, synthesize, and interpret the information you read in some meaningful way.

It is not enough to simply present the material you have found, you must go beyond that and explain its relevance and significance to the topic at hand.

Establish a clear thesis from the onset of your writing and examine which pieces of your reading help you in developing and supporting the ideas in your thesis.

Use only academic sources.

A review essay reviews the academic body of literature—articles and research presented in academic journals. Lay periodicals such as, Discover , Scientific America , or Popular Science , are not adequate sources for an academic review essay.

If you are having trouble finding the academic journals in your field, ask one of your professors or a reference librarian.

Document your sources.

The material that you discuss in a review essay is obviously not your own, therefore it is crucial to document your sources properly. Proper documentation is crucial for two reasons: 1. It prevents the writer from being accused of plagiarism and 2. It gives the reader the opportunity to locate the sources the writer has reviewed because they may find them valuable in their own academic pursuits. Proper documentation depends on which style guide you are following.

Quote sparingly and properly.

No one wants to read a paper that is simply a string of quotes; reserve direct quotations for when you want to create a big impact. Often times the way a quote is written will not fit with the language or the style of your paper so paraphrase the authors words carefully and verbage as necessary to create a well formed paragraph.

Choose an informative title.

The title you choose for your review essay should give some indication of what lies ahead for the reader. You might consider the process you took in narrowing your topic to help you with your title—think of the title as something specific rather than a vague representation of your paper's topic. For example the title Wastewater Treatment might be more informative if rewritten as The Removal of Cloroform Bacteria as Practiced by California's Municipal Water Treatment Facilities .

Consider your audience.

More than likely your audience will be your academic peers, therefore you can make a couple assumptions and choose a writing style that suits the audience. Though your audience may lack the detailed knowledge you have about your topic, they do have similar background knowledge to you. You can assume that you audience understands much of the technical language you have to use to write about your topic and you do not have to go into great detail about background information.

Elements of a Review Essay

This guide explains each section of a review essay and gives specific information about what should be included in each.

On the title page include the title, your name, and the date. Your instructor may have additional requirements (such as the course number, etc.) so be sure to follow the guidelines on the assignment sheet. Professional journals may also have more specific requirements for the title page.

An abstract is a brief summary of your review. The abstract should include only the main points of your review. Think of the abstract as a chance for the reader to preview your paper and decide if they want to read on for the details.

Introduction

The introduction of your review should accomplish three things:

• It may sound redundant to "introduce" your topic in the introduction, but often times writer's fail to do so. Let the reader in on background information specific to the topic, define terms that may be unfamiliar to them, explain the scope of the discussion, and your purpose for writing the review.
• Think of your review essay as a statement in the larger conversation of your academic community. Your review is your way of entering into that conversation and it is important to briefly address why your review is relevant to the discussion. You may feel the relevance is obvious because you are so familiar with the topic, but your readers have not yet established that familiarity.
• The thesis is the main idea that you want to get across to your reader. your thesis should be a clear statement of what you intend to prove or illustrate by your review. By revealing your thesis in the introduction the reader knows what to expect in the rest of the paper.

The discussion section is the body of your paper. The discussion section contains information that develops and supports your thesis. While there is no particular form that a discussion section must take there are several considerations that a writer must follow when building a discussion.

• A review essay is not simply a summary of literature you have reviewed. Be careful not to leave out your own analysis of the ideas presented in the literature. Synthesize the material from all the works—what are the connections you see, or the connections you are trying to illustrate, among your readings.

A review essay is not a pure summary of the information you read for your review. You are required to analyze, synthesize, and interpret the information you read in some meaningful way. It is not enough to simply present the material you have found, you must go beyond that and explain its relevance and significance to the topic at hand. Establish a clear thesis from the onset of your writing and examine which pieces of your reading help you in developing and supporting the ideas in your thesis.

• Keep your discussion focused on your topic and more importantly your thesis. Don't let tangents or extraneous material get in the way of a concise, coherent discussion. A well focused paper is crucial in getting your message across to your reader.
• Keeping your points organized makes it easier for the reader to follow along and make sense of your review. Start each paragraph with a topic sentence that relates back to your thesis. The headings used for this guide give you some idea of how to organize the overall paper, but as far as the discussion section goes use meaningful subheadings that relate to your content to organize your points.
• Your thesis should illustrate your objectives in writing the review and your discussion should serve to accomplish your objectives. Make sure your keep your discussion related to the thesis in order to meet your objectives. If you find that your discussion does not relate so much to your thesis, don't panic, you might want to revise your thesis instead of reworking the discussion.

Conclusions

Because the conclusions section often gets left for last it is often the weakest part of a student review essay. It is as crucial a part of the paper as any and should be treated as such.

A good conclusion should illustrate the key connections between your major points and your thesis as well as they key connections between your thesis and the broader discussion—what is the significance of your paper in a larger context? Make some conclusions —where have you arrived as a result of writing this paper?

Be careful not to present any new information in the conclusion section.

Here you report all the works you have cited in your paper. The format for a references page varies by discipline as does how you should cite your references within the paper.

Bastek, Neal. (1999). Review Essays for the Biological Sciences. Writing@CSU . Colorado State University. https://writing.colostate.edu/guides/guide.cfm?guideid=79

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In this course you have learnt about the subcellular components of cells and how they are studied. Cells in multicellular organisms, particularly in animals, are specialised to perform different functions; the properties, abundance and distribution of the cytoskeleton and organelles allow, and indeed underpin, this functional and structural diversity. Your study of this course has provided you with a general understanding of cellular architecture and its relationship to different processes in the cell. This sets the scene for further studies in cell biology.

• Biology Assignment Mastery: Proven Tips for Excellence

How to Write an A+ Biology Assignment: Tips and Tricks

Biology assignments can be both fascinating and challenging, requiring a blend of scientific knowledge and effective communication skills. Whether you're a high school student or pursuing a degree in biology, mastering the art of crafting an A+ biology assignment is crucial. In this blog, we will explore valuable tips and tricks to help you excel in your biology assignments , ensuring you not only understand the subject matter but also present your ideas in a clear and compelling manner.

As students endeavor to conquer the challenges posed by biology assignments, the journey begins with a fundamental step: understanding the assignment itself. Decoding the assignment prompt is akin to unraveling a scientific mystery. Identify key terms, grasp the nuances, and create a roadmap for your exploration. This initial deciphering sets the stage for a focused and well-structured response. Here, a Biology Assignment helper can play a pivotal role, guiding you through the intricate details of the task at hand.

Once the assignment prompt is deciphered, the spotlight turns to the realm of research. A meticulous exploration of reputable sources, including scientific journals, textbooks, and online databases, is imperative. Gathering a wealth of information enables you to build a robust foundation for your assignment. Take note of key concepts, experimental findings, and contrasting perspectives, organizing your research systematically. The journey of a biology assignment is much like a scientific expedition, where the quality of your research determines the richness of your discoveries.

With the assignment prompt decoded and research arsenal in hand, the crafting phase unfolds. Structuring your assignment is an art that requires finesse. Begin with a succinct introduction that not only captures the essence of your assignment but also serves as a guide for your reader. Introduce your audience to the fascinating world of your chosen biological topic. Here, the role of a Biology Assignment helper becomes evident in steering you towards a compelling introduction that sets the tone for the entire paper.

The body of your assignment is where the scientific narrative takes center stage. Divide it into logical sections, each addressing a specific facet of your topic. Rigorously adhere to the assignment prompt, ensuring that each segment contributes meaningfully to the overall coherence of your paper. As you navigate through complex biological concepts, employ visuals such as diagrams and charts to enhance clarity. The strategic use of visuals not only aids in comprehension but also showcases your mastery of scientific communication.

The pinnacle of your biology assignment journey lies in the conclusion. Summarize key points, reiterate the significance of your findings, and leave a lasting impression on your reader. A well-crafted conclusion reinforces the strength of your argument and leaves no room for ambiguity. This structured approach not only enhances the readability of your assignment but also showcases your ability to organize and present complex information with finesse.

Mastering the art of scientific writing is a parallel journey that runs throughout the assignment creation process. Clear and precise communication is paramount in the realm of biology. Avoid unnecessary jargon, define technical terms judiciously, and let the clarity of your writing shine through. Precision is the bedrock of scientific writing, where each statement is a carefully calibrated expression of accurate scientific knowledge.

Understanding the Assignment

In the realm of academia, decoding the assignment prompt is akin to deciphering a scientific blueprint, setting the stage for a successful journey through the intricate landscape of biology assignments. This initial step, often underestimated, holds the key to unlocking the potential for a well-structured and focused response that can elevate your work to A+ status.

The assignment prompt serves as your guiding beacon, providing valuable insights into the expectations and requirements of your task. Take the time to dissect the prompt meticulously, identifying key terms that shape the trajectory of your response. Terms such as 'analyze,' 'compare,' or 'contrast' serve as signposts, signaling the type of engagement expected. Understanding these cues is crucial in tailoring your approach to meet the specific demands of the assignment.

Moreover, the assignment prompt may contain hidden gems—specific topics, questions, or themes that serve as the foundation for your exploration. Create a checklist to ensure you cover all aspects outlined in the prompt, leaving no stone unturned in your quest to deliver a comprehensive and well-rounded response. This meticulous approach not only demonstrates your attention to detail but also positions you to address the assignment prompt with precision and depth.

In the midst of this decoding process, consider seeking the assistance of a Biology Assignment helper. This can be a mentor, teacher, or online resource that specializes in guiding students through the intricacies of biological assignments. A Biology Assignment helper can provide valuable insights, helping you navigate the nuances of the task and offering clarity on specific concepts that may seem perplexing at first glance.

Understanding the assignment goes beyond a superficial grasp of the task at hand; it involves immersing yourself in the overarching purpose and objectives. Why has this specific topic been chosen? What is the instructor seeking to assess or explore through this assignment? These questions delve into the heart of the assignment's intent, guiding you to tailor your response in a manner that aligns with the educational goals of the task.

Once you have decoded the assignment prompt and embraced the underlying objectives, you are equipped with the blueprint for success. This understanding becomes the scaffolding upon which you can construct a well-organized, focused, and purposeful biology assignment. It positions you to delve into the next phases of the assignment creation process—research, structuring, and scientific writing—with clarity and purpose.

In essence, understanding the assignment is the foundational step that shapes the entire trajectory of your biology assignment journey. It is the compass that directs your exploration, ensuring that every step you take aligns with the objectives outlined in the assignment prompt. Embrace this decoding process with enthusiasm and diligence, for it is the key to unlocking the full potential of your academic prowess in the captivating world of biology assignments. Happy exploring!

Decoding the Assignment Prompt

Before diving into the research and writing process, take the time to thoroughly understand the assignment prompt. Identify key terms, such as 'analyze,' 'compare,' or 'contrast,' to determine the type of response expected. If the prompt includes specific topics or questions, make a checklist to ensure you cover all aspects. Decoding the assignment prompt is the first step towards a well-structured and focused biology assignment. In the intricate landscape of academic endeavors, decoding the assignment prompt serves as the crucial compass, illuminating the path to a successful biology assignment. This nuanced process involves more than a cursory glance; it requires a meticulous unraveling of the prompt's intricacies to discern its underlying expectations and objectives.

Key to this decoding process is the identification of operative terms that act as beacons guiding your response. Terms like 'analyze,' 'compare,' or 'contrast' provide crucial insights into the type of engagement expected, shaping the nature of your exploration. Understanding these cues is akin to deciphering a code, allowing you to tailor your approach with precision.

Moreover, within the folds of the assignment prompt often lie specific topics, questions, or themes that compose the essence of your task. Creating a checklist to ensure comprehensive coverage of these elements ensures that no aspect remains unexplored. This thorough approach not only showcases your attention to detail but also positions you to meet the nuanced requirements of the assignment head-on.

Consider the assignment prompt as a rich source of information, providing clues not only about what to include but also about the overarching purpose. Why has this specific topic been chosen? What educational objectives does the instructor aim to assess through this assignment? These questions guide you beyond surface-level comprehension, allowing you to align your response with the core intent of the task.

The decoding process becomes even more enriching when complemented by a Biology Assignment helper—a mentor, teacher, or online resource specializing in guiding students through the intricacies of biological assignments. Such assistance can provide valuable insights, offering clarity on specific concepts and ensuring that your response resonates with the assignment prompt's unique demands.

Research Strategies for Biology Assignments

Once you've grasped the assignment requirements, embark on a strategic research journey. Utilize reputable sources such as scientific journals, textbooks, and online databases to gather relevant information. Take notes on key concepts, experimental findings, and any opposing viewpoints. Organize your research systematically, making it easier to integrate into your assignment later. Remember, a well-researched paper is built on a foundation of credible and up-to-date information.

Embarking on the journey of a biology assignment is akin to setting sail on the vast seas of scientific knowledge. To navigate these waters successfully, one must adopt effective research strategies that not only yield a wealth of information but also ensure the integration of credible and relevant content into the assignment.

The cornerstone of successful research lies in the selection of reputable sources. Scientific journals, authoritative textbooks, and online databases become your compass, guiding you toward a treasure trove of information. Ensure that the sources you consult are peer-reviewed, as this guarantees a level of credibility and accuracy essential for a biology assignment. A Biology Assignment helper, whether a mentor or an online resource, can provide guidance in identifying the most reliable sources specific to your topic.

As you delve into the scientific literature, take meticulous notes on key concepts, experimental findings, and any opposing viewpoints. Organize your notes systematically, creating a structured repository of information that will serve as the building blocks for your assignment. This process not only aids in synthesizing information but also facilitates the seamless integration of diverse perspectives into your narrative.

Consider the specificity of your biology assignment and tailor your research accordingly. If the task involves a specific biological process or phenomenon, focus your efforts on gathering in-depth information related to that aspect. Conversely, if the assignment demands a comparative analysis, explore a breadth of literature to present a well-rounded perspective. Strategic research is not merely about accumulating information; it's about curating a selection that aligns with the unique demands of your assignment.

Visual aids are powerful tools in the realm of biology assignments. Utilize diagrams, charts, and illustrations to complement your textual content. Visuals not only enhance the clarity of your presentation but also provide a visual summary of complex biological processes. A well-crafted visual can communicate intricate details more effectively than paragraphs of text, making your assignment more engaging and comprehensible.

In the midst of your research, be attuned to emerging trends and recent developments in the field. Biology is a dynamic discipline, and staying abreast of the latest findings adds a contemporary edge to your assignment. Include recent studies, breakthroughs, or controversies related to your topic, demonstrating not only a mastery of foundational knowledge but also an awareness of the evolving nature of biological science.

Crafting a Stellar Biology Assignment

Crafting a stellar biology assignment involves a delicate interplay of scientific knowledge, organizational finesse, and effective communication. As you embark on this journey, envision your assignment as a canvas waiting to be painted with the richness of biological concepts. Here, we explore the key elements that transform your assignment from a mere compilation of information to a masterpiece that captivates and educates.

The first stroke on your canvas is the introduction. Think of it as the opening scene in a scientific narrative. Begin with a concise overview of your topic, setting the stage for what is to follow. Clearly articulate the purpose of your assignment and provide a roadmap for the reader. The introduction is not merely a formality; it's an invitation to explore the intriguing world of your chosen biological subject.

Structure becomes the scaffolding that supports the entire assignment. Divide the body of your work into logical sections, each addressing a specific aspect of the topic. Align these sections with the requirements of the assignment prompt, ensuring that your exploration is both comprehensive and focused. This structured approach not only enhances readability but also showcases your ability to organize complex information coherently.

Within each section, let the narrative flow seamlessly. Transition between ideas with clarity, guiding the reader through the intricacies of biological concepts. If your assignment involves presenting experimental findings, present them in a chronological or logical sequence. The goal is to create a narrative thread that the reader can follow effortlessly. A well-structured and fluid narrative reflects not only your understanding of the content but also your skill in presenting it effectively.

Visual elements are the vibrant hues that add depth to your assignment. Integrate diagrams, charts, and illustrations strategically. Visual aids not only break the monotony of text but also serve as powerful tools for conveying complex biological processes. Ensure that each visual element is relevant and enhances the reader's comprehension. The artful inclusion of visuals demonstrates your ability to communicate scientific concepts both verbally and visually.

As you approach the conclusion, envision it as the grand finale of your scientific performance. Summarize key findings, reiterate the significance of your research, and leave a lasting impression. The conclusion is not a mere repetition of what has been said; it's an opportunity to showcase the broader implications of your work. Connect your findings to the larger context of biological science, emphasizing the relevance and impact of your exploration.

The art of scientific writing is the brushstroke that ties it all together. Prioritize clarity and precision in your language. Define technical terms judiciously, avoiding unnecessary jargon. Each sentence should contribute to the overall coherence of your assignment. Scientific writing is not just about conveying information; it's about conveying it with accuracy, clarity, and a touch of elegance.

The Art of Structuring: Introduction, Body, and Conclusion

A coherent structure is vital for a biology assignment that flows seamlessly. Begin with a concise introduction that outlines the purpose of your assignment and provides a roadmap for the reader. The body of your assignment should present your arguments, supported by evidence from your research. Divide it into logical sections, each addressing a specific aspect of the topic. Conclude your assignment by summarizing key points and highlighting the significance of your findings. A well-structured paper not only enhances readability but also showcases your ability to organize complex information. In the intricate world of biology assignments, mastering the art of structuring is akin to wielding a craftsman's tools to carve a coherent and compelling narrative. The introduction, body, and conclusion serve as the fundamental pillars of this structure, each playing a unique role in transforming your assignment into a well-organized and impactful piece of scientific communication.

The introduction acts as the gateway, inviting the reader into the realm of your chosen biological topic. Think of it as the opening scene of a captivating scientific story. Begin with a succinct overview of the subject, clearly stating the purpose of your assignment. A well-crafted introduction sets the tone, providing a roadmap that guides the reader through the upcoming exploration. It's not merely a formality; it's an opportunity to captivate your audience and generate interest in the biological journey you are about to unfold.

Within the body, consider visual aids as the architects of clarity. Integrate diagrams, charts, and illustrations strategically to enhance the reader's understanding of complex biological concepts. A well-chosen visual is not a mere embellishment; it is a powerful tool that reinforces your written content, making it more accessible and engaging. The art of structuring extends beyond words, embracing the visual elements that enrich your scientific narrative.

The art of structuring is not just a mechanical process of arranging words; it is a thoughtful orchestration of ideas that guides the reader through a seamless and impactful exploration of biology. From the inviting introduction that sparks curiosity, through the structured body that unveils the scientific narrative, to the conclusive finale that leaves a lasting imprint, each element contributes to the overall craftsmanship of your assignment. Mastering the art of structuring ensures that your biological journey is not only informative but also a pleasure to traverse. Happy structuring!

Mastering Scientific Writing: Clarity and Precision

Biology assignments often involve intricate scientific concepts that require clear and precise communication. Avoid unnecessary jargon and prioritize clarity in your writing. Define technical terms when first introduced and use visuals like diagrams or charts to illustrate complex processes. Precision is key in scientific writing, so ensure your statements are accurate, supported by evidence, and free of ambiguity. Remember, effective communication of scientific ideas is as crucial as the ideas themselves.

In the realm of biology assignments, mastering scientific writing is akin to wielding a precision instrument. Clarity and precision serve as the guiding principles that transform complex biological concepts into a coherent and accessible narrative.

Clarity is the beacon that illuminates your scientific communication. Prioritize straightforward language that avoids unnecessary jargon, ensuring that your ideas are accessible to a broad audience. Define technical terms when introduced, providing a clear pathway for readers to navigate through the intricacies of biological science. A well-crafted sentence should not leave room for ambiguity; instead, it should serve as a crystal-clear conduit for the transmission of scientific knowledge.

Precision is the bedrock upon which scientific writing stands. Each word should carry the weight of accuracy, and every statement should be supported by concrete evidence. Avoid vague expressions and embrace specificity. Precision is not merely a stylistic choice; it is a commitment to the integrity of scientific discourse. Your writing should mirror the meticulous nature of scientific inquiry, leaving no room for misinterpretation or misunderstanding.

Consider scientific writing as a form of elegant simplicity. Communicate your ideas with clarity, ensuring that the reader can effortlessly follow the logical progression of your arguments. Whether describing biological processes, presenting experimental findings, or analyzing data, each sentence should contribute to the overall precision of your scientific expression. The goal is not just to convey information but to convey it with a level of accuracy that reflects your mastery of the subject matter.

Mastering the art of crafting an A+ biology assignment involves a multifaceted approach that combines diligent research, effective organization, and clear communication. By following the comprehensive tips and tricks outlined in this guide, students can significantly enhance their writing skills, ensuring they not only meet but exceed the expectations of their instructors.

To embark on a successful assignment, it is crucial to begin the process early. This allows ample time for in-depth research, ensuring a thorough understanding of the biological concepts at hand. Adequate time also permits thoughtful planning, enabling students to organize their thoughts coherently and structure their assignment in a logical manner.

Effective organization is a cornerstone of a compelling biology assignment. Create a well-defined outline to guide your writing, ensuring that each section flows seamlessly into the next. A clear structure not only facilitates the reader's understanding but also reflects positively on the writer's ability to communicate complex ideas.

Moreover, staying focused on the assignment's objectives is paramount. Clearly articulate the purpose of your work and ensure every paragraph contributes directly to that goal. Avoid unnecessary information that may dilute the clarity of your message. A concise, targeted approach demonstrates a keen understanding of the subject matter and enhances the overall quality of your assignment.

Revision is a critical step in the writing process. Take the time to review and refine your work, checking for clarity, coherence, and grammatical accuracy. Solicit feedback from peers or instructors to gain valuable perspectives and identify areas for improvement. Embrace a growth mindset, viewing each revision as an opportunity to refine your skills and produce a polished, high-quality assignment.

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National Research Council (US) Committee on Biomolecular Materials and Processes. Inspired by Biology: From Molecules to Materials to Machines. Washington (DC): National Academies Press (US); 2008.

Inspired by Biology: From Molecules to Materials to Machines.

• Hardcopy Version at National Academies Press

6 Conclusions and Recommendations

Over a decade ago, the National Research Council published an optimistic report assessing the field of biomolecular materials. 1 This committee’s survey of biomolecular materials and processes has led to the conclusion that the situation today is qualitatively different from that which existed a decade or even 5 years ago. It is an especially exciting time at the intersection of the physical, materials, and biological sciences. New ways to measure, manipulate, and compute properties of biological systems are making it possible to learn the principles that govern their function. When coupled with the advances that occurred in hard and soft condensed matter research, this knowledge of principles offers the real possibility of creating materials that can perform diverse functions with biomimetic precision. These materials, in turn, will impact technologies that will further our nation’s progress in areas such as energy independence, therapeutics and diagnostic tools, and devices for sensing biological and chemical threats. By pursuing the research outlined in this report, scientists are expected to gain a dramatically better understanding of basic principles underlying the complex emergent behavior of biological systems.

It will be difficult to realize this promise, however, if steps are not taken to evolve the infrastructure and organizations that support research and education in this field. It is the committee’s view that the following issues demand immediate attention.

• SUPPORTING INTERDISCIPLINARY RESEARCH

Fundamental new insights into how biological systems function and how bioinspired materials and processes can be created require contributions from different disciplines. Such interdisciplinary research efforts are growing organically in the scientific community at a fast pace and will undoubtedly lead to important advances. Several Nobel prizes (many to European scientists) have been awarded for work at the crossroads of these disciplines. However, the U.S. research community has not yet developed a culture that adequately supports interdisciplinary science.

Recommendation 1: The Department of Energy (DOE), the National Insti tutes of Health (NIH), the National Science Foundation (NSF), and other relevant departments and agencies should jointly sponsor programs of innovative research at the intersection of different disciplines. Initiatives of this type will provide incentives for universities to work across traditional departmental boundaries. The Office of Science and Technology Policy (OSTP) should take the lead in coordinating such programs.

Currently, no federal agency has ownership of research at the intersection of disciplines. For example, NSF and DOE do not support research that impacts mitigation of disease, which is viewed as the purview of the NIH. At the same time, the NIH often looks somewhat warily at research that includes a strong component rooted in the physical sciences. This situation makes it difficult to advance some of the most promising research efforts at the crossroads of disciplines. Some important efforts have been made by individual agencies (for example, the NIH Roadmap Initiative 2 ), but these efforts are necessarily small because resources for the fields traditionally supported by a particular agency are shrinking. A comprehensive plan that involves the main federal agencies and avoids budgetary duplication is required. The committee recommends that the Office of Science and Technology Policy (OSTP) take the lead here, because it can work with the Office of Management and Budget (OMB) and the federal funding agencies to maximize taxpayer investment in research at the crossroads of disciplines—a type of research that the committee believes is critically important.

• DEVELOPING AND EVALUATING PROGRAMS FOR INTERDISCIPLINARY EDUCATION

The U.S. higher education system has been dominant in the world for over eight decades. An important reason is that education and research are inextricably intertwined at U.S. universities. Interdisciplinary research should be accompanied now by the development of educational programs that train engineers and scientists who are easily able to cross disciplinary boundaries. Such programs are important because success in fundamental interdisciplinary research and its translation into commercial products will not be possible without such a pool of scientists and engineers. A knowledge-based economy will be important for the future in the United States, and interdisciplinary education will be one of the pillars supporting this enterprise.

Recommendation 2: University physics, chemistry, biology, materials science, mathematics, and engineering departments and medical schools should jointly examine their curricula, identifying ways to prepare scientists and engineers for research at the intersection of the physical sciences, engineer ing, and the life sciences. The educational programs being created should be evaluated from a wide range of viewpoints, including input from leaders in industry and at the national laboratories.

Efforts to educate students on topics in multiple disciplines are currently under way, and they are based on disparate philosophies. One extreme is to have a discipline-free education that exposes a student to a wide variety of subjects that are of current societal relevance and of interest to that student. This approach could produce graduates who have no in-depth knowledge of any particular area of science or engineering. Such a deficiency could be problematic since knowing how to learn a topic in detail will allow us to one day learn another topic in depth. At the other extreme is an in-depth education in a traditional discipline, but with an emphasis on exposure to other fields of inquiry. For example, some universities are experimenting with requiring a secondary major. This necessarily means fewer courses in the primary major, which impedes the design of a curriculum that provides both depth in one field and adequate exposure in others. Another recent development is the emergence of educational units (for example, biological engineering departments) that aim to bring together parts of other disciplines. Yet other programs are developing courses based on case studies. Issues related to the balance between breadth and depth of knowledge acquired by students are pertinent for these models as well.

It is too early to assess the strengths and weaknesses of these different models, but planning for such assessments should be initiated soon. An important quality of the evaluation process is that it should be continual, and an important component would be direct input from outside the universities. Industry input is crucial because that sector plays such an integral role in this field, and the need to prepare graduates who can step into industrial jobs is so critical. Developing and evaluating interdisciplinary education models is essential for achieving the leadership goals of the America Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science (COMPETES) Act, Public Law No. 110-69. 3

It will also be important to continue to develop short, but intense, courses to train physical scientists in the methods and principles of the biological sciences and to train biologists in the tools and approaches of the physical and engineering sciences. A few successful programs of this type are available (at for example, Woods Hole, the California Institute of Technology, and Cold Spring Harbor), but as interdisciplinary research flourishes, more such programs will be required. There is a pressing need for courses that communicate fundamental physicochemical concepts to biologists using the mathematical knowledge common to that community. Such courses would facilitate meaningful dialogue between biologists and physical scientists and engineers.

Recommendation 3: DOE, NIH, NSF, and other relevant departments and agencies should support the development of 1- or 2-week summer courses to train physical scientists and engineers in the tools and concepts of biology and medicine and, conversely, biologists in the tools and concepts of the physical sciences. Special attention should be given to finding ways of com municating fundamental physicochemical concepts to biologists using the mathematical knowledge common to the biology community. Such summer courses would help bridge the physical and life sciences communities, allow ing them to exploit research opportunities at the intersection of the fields.

Federal funding agencies should make available resources to support and encourage the universities and individuals who wish to develop such courses. Similarly, real incentives need to be provided for the writing of textbooks for such courses. A particularly attractive model would be a book co-written by individuals who were trained in disparate fields but are working in the same interdisciplinary research field. The current academic system does not provide enough reward for writing such a badly needed book.

• EMPHASIZING BOTH FUNDAMENTAL AND APPLIED SCIENCES

Research in biomolecular materials and processes will impact society and technology in the ways described in Chapters 2 through 5 of this report. As such, both fundamental and applied research should be emphasized.

Recommendation 4: DOE, NIH, NSF, and other relevant departments and agencies should collaborate to link fundamental research with commercial applications. While it is imperative to recognize and exploit the connections between fundamental advances and opportunities to transition them into practice, curiosity-driven fundamental research on outstanding unsolved questions should be encouraged, because it could lead to unforeseen tech nological advances.

The committee especially emphasizes the importance of fundamental research. In recent years, the connections between fundamental and applied research have been encouraged, and this trend should continue. But fundamental research in the physical sciences has not been supported adequately. Yet, as described in Chapters 2 through 5 of this report, some fundamentally new advances are required (for example, understanding materials far from equilibrium) which are expected to elucidate important basic questions pertinent to biological function and bioinspired materials. This knowledge could provide the United States with the capability of developing revolutionary new technologies. It is important to emphasize that the recommendation for increased support of the basic sciences does not imply there should be a lesser emphasis on applications—basic and applied research are two sides of the same coin. The United States cannot afford to lag behind countries in Europe and Asia in applied research, and it can aim to continue to be the singular leader in paradigm-changing fundamental research. Other nations are increasing investments in both these categories.

• DEVELOPING AND EVALUATING NATIONAL FACILITIES BASED ON MIDRANGE INSTRUMENTS

National instrumentation facilities have greatly aided the scientific enterprise in the United States. In the past, most such facilities were built around a single, large centralized resource (for example, a synchrotron light source or a nuclear reactor that produces neutrons). Interdisciplinary research in biomolecular materials and processes calls for diverse instrumentation not usually available in a single laboratory. Interdisciplinary collaboration between researchers with complementary expertise is one solution to this problem. Some universities and research centers are building private facilities that house instrumentation shared by the local com munity of researchers. But many researchers have not had access to such facilities. Now, however, national facilities that house clusters of small to midrange instrumentation and associated human expertise are beginning to provide this access.

Recommendation 5: DOE should continue to evaluate the effectiveness of recently created facilities to provide access to midrange instrumentation and computational facilities for the advancement of interdisciplinary research in nanoscience and technology. Based on what is learned from this evalua tion, analogous, but distinct, centers could be created to facilitate research in biomolecular materials and processes.

Careful evaluation of the successes and failures of recently created facilities at DOE laboratories (for example, the Molecular Foundry at Lawrence Berkeley National Laboratory) will be important for gauging the effectiveness of this model. This evaluation should address questions that include whether the facility is effective in aiding research across the country (rather than just the local area), and whether universities that otherwise lack access to such facilities are benefiting from them.

NRC, Biomolecular Self-Assembling Materials: Scientific and Technological Frontiers , Washington, D.C.: National Academy Press, 1996.

More information on the NIH Roadmap Initiative is available at http://nihroadmap ​.nih.gov/ . Last accessed March 27, 2008.

A fact sheet on the America COMPETES Act is available at http://www ​.whitehouse ​.gov/news/releases/2007/08/20070809-6 ​.html . Last accessed March 27, 2008.

• Cite this Page National Research Council (US) Committee on Biomolecular Materials and Processes. Inspired by Biology: From Molecules to Materials to Machines. Washington (DC): National Academies Press (US); 2008. 6, Conclusions and Recommendations.
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DePaul University Fires Biology Professor For Israel-Hamas Class Assignment

CHICAGO (AP) — DePaul University said it dismissed a part-time biology instructor after she gave an optional assignment related to the Israel-Hamas war.

Anne d’Aquino told students in May that they could write about the impact of “genocide in Gaza on human health and biology.” The theme of the spring class at the Chicago school was how microorganisms cause disease.

DePaul said some students “expressed significant concern” about politics in a science class.

“We investigated the matter, spoke with the faculty member, and found it had negatively affected the learning environment by introducing extraneous political material that was outside the scope of the academic subject as outlined in the curriculum,” DePaul said Friday in a statement.

The school noted an email with the assignment expressed support for people “resisting the normalization of ethnic cleansing.”

“The class was provided a new instructor, and the faculty member has been released from their appointment as a part-time faculty member,” DePaul said.

D’Aquino is appealing her dismissal.

About 50 people protested last Thursday in support of her, waving Palestinian flags, the Chicago Sun-Times reported.

“My termination was a breach of my academic freedom and another example of this administration’s efforts to twist any discussions of Palestine and Palestinian liberation language into false claims of antisemitism,” d’Aquino said at the demonstration.

She said the assignment was relevant, noting that scientists have warned about the spread of disease in Gaza due to malnutrition and a lack of water and adequate sanitation.

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DePaul adjunct professor fired for optional assignment on how 'genocide in Gaza' impacts health and biology

Students delivered a petition calling for the reinstatement of anne d’aquino on thursday morning. she was fired on may 8 after she offered an optional assignment, asking students to analyze the impact of “the genocide in gaza on human health.”.

Anne d’Aquino spoke to reporters with pro-Palestinian demonstrators standing behind her.

Jessica Ma/Chicago Sun-Times

A DePaul University adjunct professor said she was fired for giving her students an optional assignment about the war in Gaza .

Anne d’Aquino, who taught in the Health Sciences Department, was terminated May 8. Two days earlier, she offered an optional assignment, asking students to evaluate the impact of the “genocide in Gaza on human health and biology,” she said.

“My termination was a breach of my academic freedom and another example of this administration’s efforts to twist any discussions of Palestine and Palestinian liberation language into false claims of antisemitism,” d’Aquino said at a news conference Thursday morning.

In support, about 50 demonstrators gathered on the corner of Seminary and Belden avenues. They waved Palestinian flags and held signs that read “Academic freedom includes Palestine.”

Students delivered a petition to the administrative office in the Monsignor Andrew J. McGowan Environmental Science and Chemistry building, calling for the reinstatement of d’Aquino. The printed copy of the petition extended 24 pages long with 1,500 signatures.

D’Aquino filed an appeal May 14, which Kristin Mathews, a university spokesperson, said will be “completed soon.”

The university did not immediately respond for comment .

• Pro-Palestinian student says University of Chicago is withholding degrees from 4 protesters

D’Aquino was halfway through her first quarter teaching at DePaul when she was fired. She taught a class called Health 194, Human Pathogens and Defense, which covers topics such as infectious disease and antibiotics.

The optional assignment suggested students review articles about the “intersection of biological sciences, health and history in Palestine.” Afterwards, students would write about the impact of “genocide on biology.”

“I’d been trying to incorporate contemporary topics for students to connect their basic biology knowledge to something that’s currently happening in the wider world,” d’Aquino said.

D’Aquino said the assignment was related to the course. For months, scientists warned about the spread of infectious disease in Gaza due to starvation, malnutrition, overcrowding, destruction of critical water and sanitation infrastructure, she said.

In the termination email, Sarah Connolly, the chair of Health Sciences, wrote that students expressed concern about “the introduction of political matters into the class.”

“That was all very sudden,” d’Aquino said. “Nobody complained to me about the assignment. I received no negative feedback on the assignment.”

A freshman in d’Aquino’s class, who did not want to be identified due to safety concerns, was “shocked, disappointed and speechless” about the firing.

After d’Aquino left, Connolly filled in as the class instructor. The student stopped attending class.

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“At Metro Chicago Hillel, we care deeply about the Jewish student experience at DePaul,” Charles, executive director of Metro Chicago Hillel, said in a statement. “Our hope is that the administration ensures that Jewish students feel safe, welcome and included in the classroom and all over campus, just like every other student.”

“[The firing] breaches everything DePaul stands for,” the student said. “Anne has love on her side.”

But Sarah van Loon, the regional manager of the American Jewish Committee Chicago, said the firing shows the “limits of protected academic freedom.”

Even if the assignment was optional, Van Loon believes d’Aquino introduced a topic that was “outside the bounds” of the class description.

“We’ve got a biology professor discussing politics in the Middle East or creating a comment about Gaza,” she said. “It really isn’t in line with what it is that they’re there to be teaching on and opens up the university to risk too.

“It doesn’t surprise me that the university felt that this was not something that upheld their standards,” Van Loon said.

But petition organizers said d’Aquino’s termination is part of a wider crackdown on academic freedom across U.S. college campuses.

Since Oct. 7, professors have said they have been fired, suspended or investigated for speaking out about the Israel-Hamas war, including at Stanford University and the City University of New York .

And the situation isn’t limited to colleges and universities.

• Chicago police clear pro-Palestinian encampment on DePaul campus

Last November, two first-grade teachers were put on leave from their jobs at a public charter school that leases space at a Jewish synagogue in Los Angeles. The action was taken over them teaching first graders what one of the teachers described on social media as “a lesson on the genocide in Palestine,” according to the Los Angeles Times.

At DePaul, Victoria Agunod, an adjunct professor in the Peace, Justice and Conflict Studies Program, said the university investigated her for her pro-Palestinian views — which was “terrifying.”

She called investigations, such as the one she went through, “political suppression.”

And d’Aquino agrees.

“[It] coincides with efforts from far-right wing members of Congress to pressure university presidents into firing faculty and disciplining students for their speech about Palestine,” d’Aquino said.

Despite the firing, d’Aquino said she hopes to see her students’ final projects.

“I’m sad that I don’t get a chance to properly say goodbye to [my students],” d’Aquino said.

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DePaul University dismisses biology professor after assignment tied to Israel-Hamas war

DePaul University adjunct professor Anne d’Aquino speaks to reporters with pro-Palestinian demonstrators standing behind her outside the North Side university’s quad, Thursday, June 6, 2024. (Jessica Ma/Chicago Sun-Times via AP)

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CHICAGO (AP) — DePaul University said it dismissed a part-time biology instructor after she gave an optional assignment related to the Israel-Hamas war.

Anne d’Aquino told students in May that they could write about the impact of “genocide in Gaza on human health and biology.” The theme of the spring class at the Chicago school was how microorganisms cause disease.

DePaul said some students “expressed significant concern” about politics in a science class.

“We investigated the matter, spoke with the faculty member, and found it had negatively affected the learning environment by introducing extraneous political material that was outside the scope of the academic subject as outlined in the curriculum,” DePaul said Friday in a statement.

The school noted an email with the assignment expressed support for people “resisting the normalization of ethnic cleansing.”

“The class was provided a new instructor, and the faculty member has been released from their appointment as a part-time faculty member,” DePaul said.

D’Aquino is appealing her dismissal.

About 50 people protested last Thursday in support of her, waving Palestinian flags, the Chicago Sun-Times reported.

“My termination was a breach of my academic freedom and another example of this administration’s efforts to twist any discussions of Palestine and Palestinian liberation language into false claims of antisemitism,” d’Aquino said at the demonstration.

She said the assignment was relevant, noting that scientists have warned about the spread of disease in Gaza due to malnutrition and a lack of water and adequate sanitation.

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JSmol Viewer

A cybertaxonomic revision of the “ crocidura pergrisea ” species complex with a special focus on endemic rocky shrews: crocidura armenica and crocidura arispa (soricidae).

Simple Summary

Graphical Abstract

1. Introduction

1.1. key provisions of the integrative approach, 1.2. cybertaxonomy of mammals, 2. materials and methods, 2.1. sampling, 2.2. the choice of species, 2.3. species determination in 3d models, 2.4. acquisition of two-dimensional images and measurement techniques, 2.5. computed x-ray micro-tomography and segmentation, 2.6. morphometric analysis and visualization of results, 2.7. statistics, 2.8. phylogenetic analysis, 2.9. terminology, 2.10. institutional abbreviations, 3.1. description of cybertypes.

Click here to enlarge figure

3.2. Phylogenetic Analysis

3.3. species comparisons, 3.4. geometric morphometric analysis, 4. discussion, 4.1. general remarks, 4.2. taxonomic remarks, 4.3. cybertaxonomy of shrews: pipeline development, 5. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Voyta, L.L.; Petrova, T.V.; Panitsina, V.A.; Bodrov, S.Y.; Winkler, V.; Kryuchkova, L.Y.; Abramson, N.I. A Cybertaxonomic Revision of the “ Crocidura pergrisea ” Species Complex with a Special Focus on Endemic Rocky Shrews: Crocidura armenica and Crocidura arispa (Soricidae). Biology 2024 , 13 , 448. https://doi.org/10.3390/biology13060448

Voyta LL, Petrova TV, Panitsina VA, Bodrov SY, Winkler V, Kryuchkova LY, Abramson NI. A Cybertaxonomic Revision of the “ Crocidura pergrisea ” Species Complex with a Special Focus on Endemic Rocky Shrews: Crocidura armenica and Crocidura arispa (Soricidae). Biology . 2024; 13(6):448. https://doi.org/10.3390/biology13060448

Voyta, Leonid L., Tatyana V. Petrova, Valentina A. Panitsina, Semyon Yu. Bodrov, Viola Winkler, Lyudmila Yu. Kryuchkova, and Natalia I. Abramson. 2024. "A Cybertaxonomic Revision of the “ Crocidura pergrisea ” Species Complex with a Special Focus on Endemic Rocky Shrews: Crocidura armenica and Crocidura arispa (Soricidae)" Biology 13, no. 6: 448. https://doi.org/10.3390/biology13060448

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• Published: 11 June 2024

Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy

• Yanmeng Wang 1 ,
• Niels Vandewalle 1 ,
• Kim De Veirman 1 , 2 ,
• Karin Vanderkerken 1 ,
• Eline Menu 1 &
• Elke De Bruyne 1  

Cell Communication and Signaling volume  22 , Article number:  320 ( 2024 ) Cite this article

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Multiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable development of drug resistance. Intense protein synthesis is a distinctive trait of MM cells, supporting the massive production of clonal immunoglobulins or free light chains. The mammalian target of rapamycin (mTOR) kinase is appreciated as a master regulator of vital cellular processes, including regulation of metabolism and protein synthesis, and can be found in two multiprotein complexes, mTORC1 and mTORC2. Dysregulation of these complexes is implicated in several types of cancer, including MM. Since mTOR has been shown to be aberrantly activated in a large portion of MM patients and to play a role in stimulating MM cell survival and resistance to several existing therapies, understanding the regulation and functions of the mTOR complexes is vital for the development of more effective therapeutic strategies. This review provides a general overview of the mTOR pathway, discussing key discoveries and recent insights related to the structure and regulation of mTOR complexes. Additionally, we highlight findings on the mechanisms by which mTOR is involved in protein synthesis and delve into mTOR-mediated processes occurring in MM. Finally, we summarize the progress and current challenges of drugs targeting mTOR complexes in MM.

Introduction

Multiple Myeloma (MM) is a hematological malignancy characterized by the accumulation of abnormal monoclonal plasma cells in the bone marrow (BM). It is the second most frequent hematological cancer and comprises 10% of all hematological malignancies, with defined clinical characteristics including hypercalcemia, renal failure, anemia, and bone lesions (CRAB) [ 1 , 2 ]. Worldwide, an estimated 160,000 people were diagnosed with MM in 2020 [ 3 ].

The discovery of novel drugs, including proteasome inhibitors (PI; Bortezomib, Carfilzomib, and Ixazomib) and immunomodulatory drugs (IMiD; Thalidomide, Lenalidomide and Pomalidomide), has significantly altered the therapeutic landscape for MM in both the frontline and relapsed/refractory setting during the past two decades. The combined application of these drugs, together with the use of myeloablative chemotherapy and autologous stem cell transplantation (ASCT), has translated into prolonged overall survival (OS) rates with reduced toxicity and improved quality of life [ 4 , 5 ]. More recently, immunotherapy has emerged as a powerful new tool to obtain durable responses in MM. This type of therapy includes monoclonal antibodies, immune checkpoint inhibitors, bispecific antibodies, chimeric antigen receptor T (CAR-T) cells, and peptide vaccines [ 6 , 7 , 8 , 9 ]. However, despite these new advancements, MM remains largely incurable due to either the occurrence of immune suppression or the development of drug resistance to multiple drug classes. With modern therapy, the first relapse typically occurs after about 3–4 years following initial diagnosis [ 2 ].

The (hypoxic) BM environment wherein the MM cells grow provides support and protection against different types of drugs. It consists of several cell types including BM stromal cells, endothelial cells, osteoclasts and osteoblasts. All these different cell types contribute to the growth and expansion of the MM clone, by providing nutrients and growth factors such as metabolites, amino acids, and cytokines. The main growth factors for MM cells include interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF). These growth factors will activate different signaling cascades with the ultimate goal to stimulate biogenesis and cell division [ 10 ].

Maintaining a stable proteome is essential for the growth and survival of every cell, yet protein synthesis (mRNA translation) and folding processes are inherently error-prone. The key steps in protein synthesis include initiation, elongation, termination and ribosome recycling [ 11 ]. Excessive protein synthesis has been associated with human cancers with elevated global translation, such as MM where there is a high production of immunoglobulins. The mammalian target of rapamycin (mTOR) kinase controls several factors involved in protein synthesis and aberrant mTOR activation through various mechanisms is frequently observed in a large portion of MM patients, contributing to cell survival, growth and drug resistance [ 12 , 13 , 14 , 15 ]. Moreover, accumulating research provides evidence that targeting the mTOR pathway can restrict protein synthesis in MM, resulting in cell death. Therefore, protein synthesis in general and the mTOR pathway specifically both represent interesting (new) targets in MM. This review will provide an update on what is known about the dysregulation of the mTOR pathway in MM and discuss promising new therapeutic strategies.

Overview of the mTOR pathway

Structure of the mtor complexes.

TOR is an evolutionarily conserved Ser/Thr-protein kinase that exists in two structurally and functionally distinct complexes, namely mTOR complex 1 (mTORC1), sensitive to the macrolide fungicide rapamycin, and the insensitive mTORC2 complex. They are both large complexes composed of multiple proteins. A regulatory-associated protein of mTOR (Raptor) and proline-rich AKT substrate 40 kDa (PRAS40) are specific to mTORC1, whereas mammalian stress-activated map kinase-interacting protein 1 (mSIN1), rapamycin-insensitive companion of mTOR (Rictor) and protein observed with rictor (Protor) 1 and 2 are exclusive components of mTORC2 (Fig.  1 ). However, they share mTOR, mammalian Lethal with Sec-13 protein 8 (mLST8), DEP-domain containing mTOR-interacting protein (Deptor) and the Telomere maintenance 2 (Tel2) and Tel2 interacting protein 1 (Tti1) complex.

Schematic representation of the mTOR signaling pathway. mTORC1 and mTORC2 share mTOR, Deptor, mLST8, Tel2 and Tti1, while Raptor and PRAS40 are unique for mTORC1 and Rictor, mSIN1, and Protor are unique for mTORC2. Growth factors stimulate PI3K to convert PIP2 to PIP3. PIP3 will then recruit PDK1, leading to phosphorylation of AKT. In addition, RAS signaling can also be activated by growth factors, promoting the activation of RAF/MEK/ERK pathway. Activated AKT and/or ERK will then phosphorylate the TSC complex and/or PRAS40, leading to the relief of their mTORC1 inhibitory activity. For the TSC complex, phosphorylation by AKT will inhibit its GAP activity towards Rheb, allowing GTP-bound Rheb to bind to and activate mTORC1. Amino acids stimulate mTORC1 by promoting the formation of Rags-v-ATPase-Regulator complexes. In addition, Gln and Asn activate mTORC1 in a RAG-independent manner via the small GTPase Arf1. In contrast, energy stress will suppress mTORC1 activity by activating AMPK, resulting in the subsequent inhibition of Raptor and activation of the TSC complex. In addition, HIF-1 will prevent mTORC1 activation by inducing BNIP3 and/or REDD1, leading to Rheb inactivation. As for mTORC2, growth factors directly phosphorylate mSIN1 in a PIP3-dependent manner or through partially activated AKT, thereby promoting mTORC2 activation. Gs-coupled β2-adrenoceptor also promotes mTORC2 activation, by stimulating cAMP accumulation and PKA activation. In addition, AMPK directly activates mTORC2. In contrast, mTORC1 inhibits mTORC2 activation, by negatively regulating PI3K/AKT signaling through S6K1. mTORC1, mTOR complex 1; mTOR, Mammalian target of rapamycin; Raptor, Regulatory-associated protein of mTOR; Deptor, DEP-domain containing mTOR-interacting protein; PRAS40, Proline-rich AKT substrate 40 kDa; mLST8, Mammalian Lethal with Sec-13 protein 8; Rictor, Rapamycin-insensitive companion of mTOR; mSIN1, Mammalian stress-activated map kinase-interacting protein 1; Protor, Protein observed with rictor; Tel2, Telomere maintenance 2; Tti1, Tel2 interacting protein 1; PI3K, Phosphatidylinositol-3-kinase; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, Phosphatidylinositol-3, 4, 5-triphosphate; PDK1, Phosphoinositide-dependent kinase 1; AKT, Protein kinase B; MEK, Mitogen-activated protein kinase; ERK, Extracellular-signal-regulated kinase; TSC, Tuberous sclerosis; GAP, GTPase-activating protein; Gln, Glutamine; Asn, Asparagine; Arf1, ADP-ribosylation factor 1; AMPK, Adenosine 5'-monophosphate-activated protein kinase; HIF-1, Hypoxia inducible factor 1; BNIP3, BCL2-interacting protein 3; REDD1, DNA damage inducible transcript 4; S6K1, Ribosomal S6 kinase; PKA, cAMP-dependent protein kinase

As a subunit of mTORC1, Raptor plays a crucial role in controlling the stability, lysosome surface localization, substrate recognition and function of mTORC1 [ 16 , 17 , 18 , 19 , 20 ]. By contrast, PRAS40 is recognized as an intrinsic inhibitory component of mTORC1, which binds to Raptor and competes with other substrates for mTORC1 binding, thereby inhibiting downstream signaling [ 21 , 22 , 23 ].

While mTORC1 has been well characterized in the last decade, knowledge on mTORC2 is only now rapidly developing. As a central member of the mTORC2 complex, mSIN1 contains an N-terminal domain (NTD), a RAS-binding domain (RBD), a conserved region in the middle (CRIM), and a pleckstrin homology (PH) domain in its C-terminal region. Both the RBD domain, through its interaction with active RAS, and the PH domain account for mTORC2 activation [ 24 , 25 ], while the CRIM domain is in charge of mTORC2 substrate recruitment [ 26 , 27 , 28 ]. In addition, mSIN1 directly interacts with Rictor through its NTD, connecting Rictor with mLST8 to stabilize the mTORC2 complex [ 28 , 29 ]. Rictor has comparable functions as Raptor, controlling mTORC2’s assembly, stability, and activity [ 30 ], whereby its C-terminal domain is responsible for mTORC2’s insensitivity to rapamycin [ 28 ]. Protor consists of two isoforms which also interact with Rictor through a conserved N-terminal region [ 31 , 32 ], however, their role remains unclear.

When evaluating the shared components, mLST8 appears to be more important for the mTORC2 complex than the mTORC1 complex. Knockdown of mLST8 blocks activation of the mTORC2 substrates, while retaining the ability to phosphorylate mTORC1 substrates [ 33 ]. Studies indicate that this is mediated by interacting with the mTORC2 cofactors Rictor and mSIN1, thereby enhancing the assembly of the complex [ 34 ]. The stabilizing proteins Tel2 and Tti1 constitutively interact with mTOR in both mTORC1 and mTORC2, and the knockdown of either Tti1 or Tel2 results in the disassembly of both complexes [ 35 ]. Finally, Deptor is a highly conserved protein that binds to mTOR through its PDZ domain, thereby inhibiting the activity of both mTORC1 and mTORC2. However, Deptor and mTOR can also regulate each other, whereby mTOR kinase activity will phosphorylate Deptor, thereby promoting its release from mTOR and reversing its activity [ 36 ].

Regulation of the mTOR complexes

The activity of mTORC1 is regulated by several factors, including growth factors, amino acids, stress signals and cellular energy (Fig.  1 ). Several growth factors can activate mTORC1 by interacting with their cell-surface receptor tyrosine kinase(s), leading to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT and RAS/ERK (extracellular-signal-regulated kinase) pathways [ 37 , 38 ]. By blocking either the tuberous sclerosis (TSC) complex or PRAS40, two mTORC1 negative regulators, AKT and ERK both positively control mTORC1 activity [ 39 , 40 , 41 ]. The TSC complex, which consists of three core subunits, TSC1, TSC2, and TBC1D7, keeps the small G-protein Rheb in an inactive state via its GTPase-activating protein (GAP) activity and by promoting Rheb ubiquitination [ 42 , 43 ]. However, upon growth factor stimulation, AKT will phosphorylate both TSC2 and the deubiquitinase ubiquitin specific peptidase 4 (USP4), resulting in the release of Rheb from the inhibitory effect of the TSC complex [ 44 ]. PRAS40 is not only a component of mTORC1, but also a substrate of mTORC1, located downstream of mTORC1 but upstream of its effectors. Therefore, it can be controlled by both AKT or mTORC1 itself. While activated AKT dissociates PRAS40 from the mTORC1 complex by phosphorylating its threonine residue (Thr246), mTORC1 directly phosphorylates PRAS40 at serine residues (Ser183 and Ser221) to impair its inhibitory action [ 45 , 46 , 47 ].

It is generally believed that amino acid signaling stimulates mTORC1 activity by regulating its subcellular localization, and Rag guanosine triphosphatases (Rags or Rag GTPases) play a crucial role in this process [ 48 , 49 ]. When amino acids are sufficiently present, active Rags form a complex with v-ATPase-Regulator and transmit amino acid signaling to the mTORC1 pathway by binding to Raptor. This process recruits mTORC1 to the lysosomal membranes, where Rheb is present, and stimulates mTORC1 activation [ 50 , 51 ]. While most amino acids activate mTORC1 through Rags, glutamine (Glu) and asparagine (Asn) appear to activate mTORC1 in a Rag-independent manner that requires the small GTPase ADP-ribosylation factor 1 (Arf1) [ 52 ]. However, the glutamine sensor and other components involved in this Rag-independent pathway in mammals remain to be studied.

Energy stress controls mTORC1 activation primarily through an adenosine 5'-monophosphate-activated protein kinase (AMPK)-dependent mechanism. Under energy stress, such as glucose deprivation, the concentration of ATP drops dramatically while the cellular levels of AMP and ADP increase. AMP binds to the γ-subunit of AMPK contributing to its activation. AMPK then transmits the energy stress signal to mTORC1 mainly through two mechanisms [ 41 , 53 ]. Firstly, AMPK activates the TSC complex, which in turn represses Rheb, thereby reducing mTORC1 activity [ 54 , 55 ]. Secondly, AMPK will directly phosphorylate mTOR and Raptor, which also appears to be required for energy stress-induced inhibition of mTORC1 [ 56 , 57 , 58 ]. Additionally, AMPK-independent mechanisms have also been discovered to regulate mTORC1 activity upon stress. For example, mTORC1 can also be inactivated by hypoxia inducible factor 1 (HIF-1), the master regulator of the cellular response to hypoxia. HIF-1, either by inducing BCL2-interacting protein 3 (BNIP3) or by activating DNA damage inducible transcript 4 (DDIT4/REDD1), prevents activation of mTORC1 via direct interaction with Rheb [ 59 , 60 , 61 , 62 ].

In comparison to mTORC1, the signals activating mTORC2 and the mechanisms involved are less understood and more complicated. Similar to mTORC1, it is generally believed that growth factor-dependent mTORC2 activation requires PI3K/PIP3. In the unstimulated state, the mSIN1 PH domain is bound to the catalytic core within mTOR, thereby impairing mTORC2 activity. Following growth factor stimulation, PIP3 not only recruits Phosphoinositide-dependent kinase 1 (PDK1) and AKT from the cytosol, it will also bind to mSIN1 to expose the catalytic core within mTOR. AKT, which is partially activated through phosphorylation of Thr308 by PDK1, will then phosphorylate mSIN1 at Thr86, leading to a conformational change and subsequent promotion of mTORC2 activity. mTORC2 will then on its turn phosphorylate AKT at Ser473, resulting in full AKT activation [ 63 , 64 ]. Additional stimuli that can trigger mTORC2 activation include adrenergic signaling via G-protein coupled receptors (GPCR), such as the β2‐adrenoceptor, which stimulates cAMP accumulation and activation of cAMP-dependent protein kinase (PKA), leading to phosphorylation of mTORC2 [ 65 ]. Also, AMPK appears to be sufficient to increase mTORC2 catalytic activity towards AKT in an mTORC1-independent manner [ 66 ]. Finally, mTORC2 activity is negatively regulated by mTORC1. Elevated mTORC1 activity upon insulin/ IGF-1signaling increases the activity of one of its direct effectors, S6K1 (see below), which in turn will phosphorylate insulin receptor substrate 1 (IRS1) on various negative regulatory sites, thereby inhibiting PI3K signaling and dampening mTORC2 [ 67 ].

Molecular mechanisms of mTOR-mediated translational control

mTOR functions as a central coordinator of cellular metabolic homeostasis in response to nutrient levels and growth signals. When ample nutrients and growth factors are present, the activation of the mTOR pathway promotes anabolic pathways, including protein and lipid synthesis, while also stimulating glycolysis and mitochondrial metabolism. Conversely, under conditions of hypoxia or energetic stress, mTOR signaling is inhibited, halting energy-consuming anabolic pathways and promoting catabolic pathways, such as autophagy [ 68 ]. In this review, we will discuss how mTORC1 and mTORC2 are involved in multiple aspects of protein synthesis, including activation of the substrates involved in mRNA translation initiation and promotion of ribosome biogenesis (Fig.  2 ).

mTOR signaling and regulation of mRNA translation. mTOR signaling controls protein synthesis via regulation of mRNA translation initiation and ribosome biogenesis. mTORC1 phosphorylates 4E-BP1, resulting in the assembly of the eIF4F translation initiation complex. In addition, mTORC1 will phosphorylate S6K1, thereby promoting translation via phosphorylation of rpS6, eIF4B, PDCD4, eIF3, SKAR, and eEF2. In addition, mTORC1 also regulates ribosome biogenesis by activating UBF and TIF-1A, while inhibiting MAF1, thereby modulating Pol I and Pol III transcription. In addition, mTORC1 promotes translation of 5'-TOP transcripts by phosphorylating LARP1. Finally, mTORC2 also regulates ribosome biogenesis by relocating Rictor to the ER. mTOR, Mammalian target of rapamycin; 4E-BP1, Eukaryotic translation initiation factor 4E-binding protein 1; eIF4F, Eukaryotic translation initiation factor 4F; S6K1, Ribosomal S6 kinase 1; mTORC1, mTOR complex 1; rpS6, Ribosomal protein S6; eIF4B, Eukaryotic translation initiation factor 4B; PDCD4, Programmed cell death protein 4; eIF3, Eukaryotic translation initiation factor 3; SKAR, S6K1 Aly/REF-like substrate; eEF2, Eukaryotic elongation factor 2; Pol I/III, RNA polymerase I/III; LARP1, La-related protein 1; mTORC2, mTOR complex 1; Rictor, Rapamycin-insensitive companion of mTOR; 5’-TOP, 5’-terminal oligopyrimidine; ER, Endoplasmic reticulum

Activation of mRNA translation initiation

When sufficient nutrients are present, mTORC1 is strongly activated, promoting protein synthesis by phosphorylating eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and p70 S6 kinase 1 (p70-S6K, also known as S6K1) in a Raptor-dependent manner [ 69 ].

To initiate mRNA translation, the mRNA first needs to be unwound or activated by the eIF4F complex, comprising the cap-binding protein eukaryotic translation initiation factor 4E (eIF4E), the RNA helicase eIF4A, and the scaffold protein eIF4G, together with the assistance of eIF4B, eIF3 and poly(A)-binding protein (PABP). In its unphosphorylated state, 4E-BP1 represses translation by binding to and sequestering eIF4E, thereby preventing its interaction with eIF4G. mTORC1 phosphorylates 4E-BP1 at several sites, causing the dissociation of 4E-BP1 from eIF4E [ 70 ]. The release of eIF4E enables association with eIF4G and the assembly of the eIF4F translation initiation complex at the 5′end of the mRNA [ 71 ]. S6K1 is the second well-established downstream effector of mTOR that is directly phosphorylated by mTOR [ 72 , 73 ]. S6K1 phosphorylates several factors participating in protein synthesis, including eIF4B, programmed cell death protein 4 (PDCD4), eIF3, eEF2, 40S ribosomal protein S6 (rpS6), and S6K1 Aly/REF-like target (SKAR). Phosphorylation of eIF4B leads to its binding with eIF4G and eIF4A, while phosphorylation of PDCD4 leads to its release from eIF4A, allowing eIF4A to interact with eIF4G. Importantly, eIF4B and PDCD4 phosphorylation by S6K1 is sufficient to maintain protein synthesis, even in the absence of 4E-BP1 [ 74 ]. Phosphorylated eIF3 will bind to the PABP regulatory protein PABP-interacting protein 1 (Paip1), thereby stabilizing the interaction between PABP and eIF4G, thus further stimulating translation [ 75 , 76 ]. The protein kinase eukaryotic elongation factor 2 kinase (eEF2k) is a negative regulator of eEF2, which becomes inhibited after phosphorylation by S6K1, thereby releasing eEF2 and allowing proper elongation [ 77 ]. Phosphorylation of rpS6 has been shown to control cell size, however its function in protein synthesis remains elusive [ 78 ]. Finally, by interacting with SKAR, S6K1 is recruited to newly synthesized mRNAs in a splicing-dependent manner [ 79 ].

Ribosome biogenesis

To cope with increased protein synthesis, mTORC1 also promotes several steps in ribosome biogenesis, including ribosomal RNA transcription, synthesis of ribosome proteins and other components required for ribosome assembly. In mammals, the ribosomes contain 4 different rRNAs involved in ribosome assembly, which are transcribed by either RNA polymerase I (Pol I) or RNA polymerase III (Pol III) [ 80 ]. Several basal factors required for Pol I-mediated transcription are regulated by mTORC1. Firstly, mTORC1 activates Pol I-mediated transcription by increasing the expression and phosphorylation of UBF, thereby facilitating the recruitment of Pol I to rDNA [ 81 ]. Secondly, mTORC1 activates TIF-1A, a transcription factor that connects Pol I with UBF to initiate the transcription of pre-ribosomal RNA [ 82 ]. Thirdly, MAF1 is a key repressor of Pol III transcription, which becomes inhibited after phosphorylation by mTORC1 [ 83 ]. In addition, mTORC1 also controls the translation of a variety of mRNAs, particularly the 5’-terminal oligopyrimidine (5’-TOP) transcripts encoding ribosomal proteins, via direct phosphorylation of the La-related protein 1 (LARP1), a repressor of ribosomal protein mRNA translation [ 84 ]. Phosphorylation of LARP1 abolishes its blockage on the assembly of the eIF4F complex [ 85 , 86 ]. Of note, enhanced ribosome biogenesis facilitates the transition of cells from an epithelial to a mesenchymal state, a process known as epithelial-mesenchymal transition (EMT). This EMT-associated ribosome biogenesis is accompanied by a pronounced increase in Rictor’s localization in the endoplasmic reticulum (ER), indicating also a regulatory role of mTORC2 in ribosome biogenesis [ 87 ].

Aberrant mTOR pathway signaling in MM cells

Over the years, dysregulation of mTOR has been associated with many diseases, such as diabetes, neurological disorders, and cancer (including MM) [ 88 ]. mTOR signaling is influenced in MM by numerous factors (Fig.  3 ), which can be subdivided in extrinsic, BM microenvironment-derived factors and intrinsic, cell-autonomous factors.

Extrinsic and intrinsic factors regulating mTOR signaling in MM. Extrinsic factors: The myeloma growth factors IL-6, VEGF and IGF-1, which are abundantly present in the BM microenvironment, all induce mTORC1 activation via PI3K/AKT signaling. In addition, cell–cell contact with BMSC and osteoblasts via RANK-RANKL binding also activates PI3K/AKT/mTOR signaling in the MM cells. In addition, Pim2 overexpression, triggered by cytokines or cell–cell contact, also leads to mTORC1 activation via phosphorylating TSC2, while the hypoxic microenvironment mediates mTORC1 activity by regulating lactate, PYCR1 and MAT2A levels. Finally, β2AR is also involved in mTOR activation. Intrinsic factors: Deptor overexpression in MM cells blocks the inhibitory effect of S6K1 on AKT, thereby activating mTORC2. In addition, (Epi)genetic alterations, such as RAS mutationsPTEN depletionoverexpression of G9a/GLP and epigenetic silencing of RASSF4, all support enhanced mTORC1 signaling. Additionally, UCHL directly promotes the assembly of eIF4F. In contrast, Fbxo9 overexpression suppresses mTORC1 signaling by selectively targeting Tel2 and Tti1 in mTORC1 for degradation, which again releases mTORC2 from the negative feedback loop with mTORC1, leading to its activation. To maintain a high rate of protein synthesis, eIF4E is overexpressed in MM. Overexpressed eIF4E in turn promotes protein synthesis by upregulating MYC. Moreover, ER stress, induced by this massive protein synthesis, suppresses mTORC1 signaling via upregulating NUPR1. IL-6, Interleukin 6; IGF-1, Insulin-like growth factor-1; BM, Bone marrow; mTORC1, mTOR complex 1; mTORC2, mTOR complex 2; BMSC, Bone marrow stromal cells; RANK, Receptor activator of nuclear factor-kB; RANKL, RANK Ligand; mTOR, Mammalian target of rapamycin; PYCR1, Pyrroline-5-carboxylate reductase 1; MAT2A, Methionine Adenosyltransferase 2α; PI3K, Phosphatidylinositol-3-kinase; AKT, Protein kinase B; 4E-BP1, Eukaryotic translation initiation factor 4E-binding protein 1; S6K1, Ribosomal S6 kinase; Deptor, DEP-domain containing mTOR-interacting protein; PTEN, Phosphatase and tensin homolog deleted from chromosome 10; GLP, G9a-like protein; RASFF4, Ras-association domain family member 4; Tel2, Telomere maintenance 2; Tti1, Tel2 interacting protein 1; Fbxo9, F-box only protein 9; mTORC2, mTOR complex 2; ER, Endoplasmic reticulum; NUPR1, Nuclear protein 1; β2AR: β2 adrenergic receptor; UCHL1: Ubiquitin C-terminal hydrolase L1; TSC2: Tuberous sclerosis; eIF4F, Eukaryotic translation initiation factor 4F; eIF4E, Eukaryotic translation initiation factor 4E

Extrinsic, BM microenvironment-derived factors

IL-6 and IGF-1, as prominent MM growth factors secreted by the BM microenvironment, activate the mTOR signaling pathway in myeloma cells, as evidenced by phosphorylation of S6K1 and 4E-BP1 upon stimulation [ 89 , 90 , 91 ]. IL-6-induced S6K1 activation can be inhibited by rapamycin, the ERK inhibitor PD98059, as well as a dominant negative mutant of AKT, suggesting that both ERK and PI3K/AKT are required for IL6-induced mTOR/S6K1 activation. In contrast, IL-6-induced phosphorylation of 4E-BP1 is only inhibited by rapamycin and the dominant negative AKT, indicating that PI3K/AKT/mTOR is sufficient for 4E-BP1 phosphorylation in MM. Similarly, for IGF-1, phosphorylation of S6K1 and 4E-BP1 can be abolished by the PI3K inhibitor LY294002 and rapamycin [ 90 , 92 ]. Importantly, IL-6 and IGF-1-induced MM cell growth can also be blocked by activation of AMPK, using metformin or the AMPK activators 5-aminoimidazole-4-carboxamide riboside (AICAr) and D942, leading to inhibition of mTOR, S6K1 and AKT phosphorylation [ 93 , 94 , 95 ]. VEGF will also trigger mTOR activation via AKT. Inhibiting VEGF by bevacizumab blocks both mTOR and the translation initiation factor eIF4E, resulting in G1 cell cycle arrest and cell death [ 96 ].

In addition to cytokines/growth factors, the mTOR pathway in MM cells is modulated through various other BM-niche related factors as well. For example, cell–cell interactions with the bone marrow stromal cells (BMSCs) and osteoblasts in the BM microenvironment, mediated by RANK-RANKL binding, foster MM cell survival, growth and drug resistance via c-Src mediated mTOR signaling [ 97 , 98 ]. Moreover, cytokines such as IL-6 and binding to BMSC will also trigger overexpression of the constitutively active serine/threonine kinase Pim2, which is essential for MM survival by phosphorylating TSC2, leading to mTORC1 activation and signaling [ 99 , 100 ].

Since the BM environment is hypoxic, it favors metabolic rewiring of MM cells, which is characteristic of a more resistant phenotype. This metabolic rewiring will also affect mTOR signaling in MM cells. We found that under hypoxic conditions, anaerobic glycolysis in MM cells leads to an accumulation of lactate in the BM environment, while metabolic enzymes, such as pyrroline-5-carboxylate reductase 1 (PYCR1) and methionine adenosyltransferase 2α (MAT2A), are also upregulated [ 101 , 102 , 103 ]. Blocking lactate secretion via inhibition of the monocarboxylate transporter (MCT), in combination with metformin, led to inhibition of mTOR signaling via activation of upstream AMPK. This in turn reduced protein synthesis, leading to caspase activation [ 101 ]. Inhibition of PYCR1 also prevented the activation of the mTOR pathway, which in turn impaired phosphorylation of 4E-BP1, eIF4e and S6K1, as well as their upstream protein PRAS40. Further analysis demonstrated that PYCR1 inhibition also reduced cellular uptake of puromycin, confirming that protein synthesis was inhibited [ 102 ]. Similarly, MAT2A inhibition also inactivated the mTOR-4E-BP1 pathway, accompanied with a decrease in protein synthesis, again resulting in MM cell death [ 104 ].

Finally, the sympathetic nervous system forms a regulatory component of the BM whereby sympathetic nerve fibers form a niche to regulate hematopoiesis during homeostasis and stress. These fibers release norepinephrine that will bind to the β2 adrenergic receptor (β2AR), found on the different cell types in the BM [ 105 ]. We found that β2AR is a poor prognostic factor in MM and that the β2AR blocker propranolol inhibited mTOR activation which led to increased apoptosis in MM cells [ 106 ].

Intrinsic, cell-autonomous factors

Aberrant deptor expression/activity.

While many human cancers bearing activated mTORC1 and mTORC2 pathways, have downregulated expression of Deptor, in MM cells, the general consensus is that Deptor acts as an oncogene, by compensating for the negative feedback from S6K1 to PI3K, thereby activating AKT [ 107 ]. Moreover, in the MM subgroups harboring a cyclin D1/D3 or c-MAF/MAFB translocation, Deptor is highly expressed, suggesting that the MAFB transcription factor regulates Deptor expression [ 108 ]. More recently, it was found that in these MM subgroups, Deptor is phosphorylated by ERK at Ser235, which maintains its stability [ 109 ]. It has also been shown that Deptor supports the high protein synthesis in MM cells by regulating the transcription of several genes involved in the maintenance of the ER such as ERLIN2, KEAP1, PSEN2 and DERL3 [ 110 ]. Accordingly, several studies have shown that inhibition of Deptor leads to increased drug sensitivity in vitro and has potent anti-tumor effects in vivo [ 107 , 111 ].

Aberrant regulators expression/activity

Genetic mutations in the activators or suppressors of mTOR signaling are common in cancers, including MM. KRAS and NRAS are both mutated in approximately 20% of newly diagnosed MM cases and play an important role in the pathogenesis, progression and prognosis of MM. Overexpression of mutated KRAS or NRAS leads to constitutive activation of the mTOR/S6K1 pathway, which was first discovered in the MM cell line ANBL6 [ 112 ]. A more recent study showed that both KRAS or NRAS knockdown decrease phosphorylation of the mTORC1 targets, S6K1 and 4E-BP1, in RAS-dependent MM lines. Of note, due to compensatory feedback signaling, NRAS knockdown also increased phosphorylation of the mTORC2 components and its downstream signaling effectors [ 113 ]. In addition, the study revealed a possible mechanism for the constitutive activation of mTOR caused by RAS mutations. The mutant isoforms of RAS were demonstrated to coordinate a signaling complex with the amino acid transporter, solute carrier family 3 member 2 (SLC3A2), and mTOR on endolysosomes directly activating mTORC1 by co-opting the amino acid sensing pathways [ 113 ]. Many MM cell lines also contain a mutation for phosphatase and tensin homolog deleted from chromosome 10 (PTEN), suggesting a growth advantage for the loss of PTEN. Indeed, these MM cells have constitutive AKT activity and have upregulated mTOR activity. This makes them particularly sensitive to mTOR inhibition, leading to cell cycle arrest [ 114 ].

Epigenetic changes can also contribute to aberrant activation of the mTOR pathway in MM cells. We showed that the mTOR pathway is regulated by the histone methyltransferases G9a and G9a-like protein (GLP) in MM. Overexpression of G9a has been reported in several cancers, including MM, correlating with disease progression, metastasis, and poor prognosis [ 115 ]. Mechanistic studies by our group revealed that targeting G9a/GLP impaired the activation of the mTOR/4E-BP1 pathway, leading to autophagy-associated apoptosis in MM [ 116 ]. Additionally, the tumor suppressive Ras-association domain family (RASSF) proteins are typically silenced in cancer cells through promotor hypermethylation [ 117 ]. We demonstrated that RASSF4 is epigenetically silenced in MM cells and that forced expression of RASSF4 increased the anti-MM effect of the MEK inhibitor trametinib via inhibition of the PI3K/mTOR pathway [ 118 ].

The germinal center B-cell oncogene ubiquitin C-terminal hydrolase L1 (UCHL1) is a highly expressed oncogene in MM cells, which encodes a deubiquitinating enzyme that regulates the balance between mTOR complexes, by reducing the non-degradative ubiquitination of Raptor in mTORC1, leading to decreased 4E-BP1 phosphorylation, while at the same time promoting mTORC2 assembly. However, in MM, it was found that UCHL1 bypasses the inhibitory effect on 4E-BP1 by directly associating with and promoting the assembly of eIF4F. Depletion of UCHL1 led to cell death both in vitro and in an orthotopic model of myeloma [ 119 ].

PI3K/TORC2/AKT signaling and survival of MM cells is also dependent on F-box only protein 9 (Fbxo9) expression, which is highly expressed in primary human MM. F-box proteins form the substrate recognition component of the SCF type of the ubiquitin ligase complex E3, thereby regulating proteolysis through the ubiquitin proteasome system (UPS). In MM, Fbxo9 regulates mTOR signaling through Tel2 and Tti1. In response to serum starvation, overexpression of Fbxo9 attenuates mTORC1 signaling via degradation of Tel2 and Tti1 within mTORC1, whereas mTORC2 signaling is maintained through the relief of the feedback inhibition, leading to constitutive active PI3K/TORC2/AKT signaling and cell survival. By contrast, loss of Fbxo9 increases the cell size and level of cap-dependent translation of a luciferase mRNA via activation of mTORC1 signaling, while BrdU uptake and cell survival were found to be reduced [ 120 ].

Aberrant protein synthesis

In contrast to other cancer cells, one of the main characteristics of MM cells is the synthesis of large amounts of immunoglobulin (Ig). To cope with this high demand of protein synthesis, eIF4E is overexpressed in myeloma cell lines and primary myeloma cells compared to plasma cells [ 121 ]. In a human xenograft mouse model of MM, stable overexpression of eIF4E dramatically accelerated tumorigenesis, whereas eIF4E knockdown impaired tumor progression [ 121 ]. Mechanistically, overexpression of eIF4E was shown to control protein synthesis in MM cells by regulating translation of mRNAs with highly complex 5'-untranslated regions, such as c-MYC [ 122 ], while eIF4E inhibition reduced the levels of c-MYC and attenuated cell survival and dexamethasone (DEX) resistance [ 123 , 124 ]. Importantly, hyperactivation of MYC, which is an essential event mediating transformation from the premalignant condition monoclonal gammopathy of undetermined significance (MGUS) to MM, has been proven to be a key factor in the regulation of ribosome biogenesis and protein synthesis [ 124 , 125 , 126 ]. MYC directly increases protein synthesis rates by controlling the expression of multiple components of the protein synthesis machinery, including ribosomal proteins (RPs and small or large ribosomal subunits, and their cofactors) and initiation factors of translation, Pol I, Pol III and rDNA [ 127 , 128 , 129 ]. Moreover, MYC can stimulate ribosomal RNA (rRNA) modifications by controlling the expression of ribonucleases, rRNA-modifying enzymes, and nucleolar proteins involved in ribosome biogenesis such as NPM, Nop52, Nop56, and DKC1. In addition, MYC protein was shown to translocate to the nucleolus where it can directly regulate rRNA synthesis by binding to E-box elements located in the rDNA promoter [ 128 , 130 ]. In this way, overexpression of MYC will lead to a substantial increase in nucleolar activity, which is needed to support enhanced protein synthesis [ 131 ].

Massive protein synthesis will also lead to high baseline levels of ER stress, triggering protective responses, such as autophagy, in MM cells [ 132 ]. Autophagy is usually considered a pro-survival mechanism that cooperates with the UPS to maintain myeloma cell homeostasis, by degrading excessive and misfolded proteins for energy recycling [ 133 ]. In MM, ER stress has been shown to promote autophagy by suppressing the PI3K/AKT/mTOR signaling pathway [ 134 ]. Nuclear protein 1 (NUPR1) is a stress-related small molecule that is abnormally expressed in MM cells. Previous studies discovered that knockdown of NUPR1 suppresses survival and growth of MM cell lines, by inducing caspase-dependent apoptosis and G0/G1 cell cycle arrest [ 135 ]. Later studies suggested that silencing of NUPR1 suppresses autophagy activities and induces autophagy-mediated apoptosis via PI3K/AKT/mTOR signaling in MM cells [ 136 ].

The mTOR pathway as a promising therapeutic target for MM

Pre-clinical studies.

Since the discovery of the important role of the mTOR pathway in the progression of MM, studies have tested the potential use of mTOR inhibitors for the treatment of MM (Table  1 ).

The mTORC1 inhibitor rapamycin (sirolimus) and the rapamycin analogue (rapalog) CCI-779 were the first to be examined in MM, and were shown to have anti-tumor effects in cells containing PTEN mutations by inducing a G1 cell cycle arrest accompanied by reduced c-MYC levels [ 114 ]. Moreover, rapamycin and CCI-779 also significantly curtailed the growth of cells containing oncogenic RAS mutants [ 112 ]. Using a myeloma xenograft model, CCI-779 was also proven to induce significant, dose-dependent anti-myeloma effects in vivo, along with upregulated p27 and downregulated cyclin D1 and c-MYC levels [ 137 ]. However, several studies also revealed major drawbacks of applying rapamycin and CCI-779. Specifically, inhibition of mTORC1 by rapamycin and CCI-779 leads to increased mTORC2 activity, thereby enhancing basal PI3K/AKT signaling resulting in drug resistance [ 138 ]. Furthermore, in all RAS-dependent MM cells, inhibition of mTORC1 activity also leads to an enhanced dependence of the MM cells on MEK and ERK signaling, consequently diminishing the drug's effectiveness [ 113 , 153 ]. This led to the recent discovery of new combination strategies using rapamycin or its analogue for the treatment of MM. For example, combination of rapamycin with perifosine, an AKT inhibitor was found to synergistically induce MM cytotoxicity by overruling the feedback activation of AKT [ 139 ]. The insensitivity of mTORC2 to rapamycin could also be bypassed by efficiently blocking both mTORC1 and mTORC2 signaling pathways using a combination of rapamycin with resveratrol, leading to reduced cell viability in the MM1.S cell line [ 140 ]. Resveratrol is a polyphenolic compound that has been reported to inhibit proliferation, induce apoptosis, and overcome chemoresistance as a single agent, by interfering with nuclear factor κB (NF-κB) and STAT3 pathways in human MM cells [ 154 ]. Also, synergy between everolimus, another rapamycin analogue, and inhibitors targeting classical mitogen-activated protein kinase (MAPK) signaling via MEK and ERK, such as trametinib, was discovered [ 113 , 141 ]. In addition, rapamycin has been shown to have synergistic antitumor effects when combined with drugs which have already entered the clinic. For one, rapamycinsynergizes with the standard of care (SoC) drug BZ [ 142 , 155 ]. Another possible combination is with the pan-histone deacetylase inhibitor (HDACi) panobinostat, which lacks therapeutic effectiveness as a single agent despite having promising anti-myeloma capabilities. One of the resistance mechanisms against panobinostat is triggered by overexpression of the C-X-C motif chemokine receptor 4 (CXCR4), which also activates mTOR signaling. Therefore, combining panobinostat with everolimus led to sustained DNA damage and irreversible proliferation suppression, resulting in the abrogation of resistance to HDACi and synergistic cell death [ 143 ]. The combination of everolimus and another HDACi entinostat has also been shown to repress oncogenic MYC and activate the Cdkn2a tumor suppressor in MM mouse models [ 144 ]. In addition, combination of rapamycin and the heat shock protein 90 (HSP90) inhibitor 17-AAG synergistically inhibited proliferation and survival of MM cells, as well as angiogenesis and osteoclast formation [ 145 ]. As mentioned above, one of the mechanisms by which cancer cells can flexibly reprogram their pathways away from specific metabolic blockages is activation of mTOR. Combination of the tyrosine kinase inhibitor ponatinib and rapamycin therefore impaired the production of ATP required for cell proliferation by targeting glycolytic reprogramming and residual OXPHOS [ 146 ].

To inhibit mTOR more effectively, a number of ATP-competitive mTOR inhibitors have been developed. Unlike rapamycin and the rapalogs, ATP-competitive mTOR inhibitors target both mTORC1 and mTORC2. TAK-228, also called MLN0128/INK128, is an oral and selective ATP site kinase inhibitor of mTOR. In MM cell lines and primary cells from patients, TAK-228 inhibits the activity of both TORC1 and TORC2, thereby reducing their survival more potently than rapamycin [ 147 ]. Pp242 (Tokinib), is another selective ATP-competitive inhibitor of mTOR that has promising anti-cancer activity in several cancer types. Compared to rapamycin, pp242 not only inhibits phosphorylation of mTORC1 substrates S6K1 and 4E-BP1, but also inhibits phosphorylation of AKT. Moreover, pp242 was shown to be more effective than rapamycin for blocking the release of eIF4E from 4E-BP1 [ 156 ]. In line with this efficient mTOR inhibition, pp242 strongly impaired survival of primary MM cells isolated from newly diagnosed patients as well as MM cell lines, as evidenced by the induction of caspase-mediated apoptosis. Importantly, the anti-MM effect of pp242 was also validated in vivo [ 148 ]. Moreover, since mTORC2 plays a major role in the angiogenic switch in MM, pp242 also reduced the angiogenic capacity of endothelial cells isolated from MGUS and MM patients and enhanced the anti-angiogenic effect of lenalidomide and BZ [ 148 , 149 ]. Unfortunately, while pp242 can overcome the feedback activation of AKT caused by the inhibition of mTORC1, it still induces activation of ERK, thus limiting its clinical translation [ 153 ]. AZD8055 is another ATP-competitive mTOR inhibitor that induces apoptosis in MM cell lines and patient cells. However, in AKT-expressing MM cell lines, AZD8055 also upregulated phosphorylation of insulin-like growth factor 1 receptor (IGF1R), which prevented apoptosis. Combination of AZD8055 and IGF1R blockers was able to inhibit the IGF1-induced phosphorylation of AKT, resulting in apoptosis of the MM cells [ 150 ].

Additionally, another novel alkaloid compound, DCZ0358, was synthetized to efficiently inhibit mTOR signaling via dual mTORC1/2 inhibition. This compound has anti-MM potential in both primary and MM cell lines as a single agent. Notably, DCZ0358 also prevented BZ-induced phosphorylation of AKT, resulting in synergistic anti-MM activity [ 151 , 157 ]. Finally, the dual class I PI3K/mTOR inhibitor NVP-BEZ235 also showed high antitumor activity in MM by regulating the mTOR2-AKT-FOXO3a-BNIP3 pathway [ 158 ]. In addition, NVP-BEZ235 induced synergistic cell death in MM cell lines when combined with BZ, dexamethasone and doxorubicin [ 152 ].

Clinical trials

Given that preclinical studies in MM were able to demonstrate anti-cancer activity of mTOR inhibitors alone or in combination with SoC drugs, several clinical trials evaluated the efficacy of mTOR inhibitors for treating MM (Table  2 ).

CCI-779 was the first mTOR inhibitor to be clinically evaluated in patients with relapsed/refractory (RR) MM. In a phase II trial, 16 patients were enrolled and received monotherapy with CCI-779 (25 mg I.V. weekly). After at least two cycles of treatment, one patient achieved a partial response (PR) and five patients achieved minimal response (MR). Time to progression (TTP) was found to be 138 days. Meanwhile, in patients with a MR or PR, inhibition of p-p70S6K and p-4E-BP1 was observed in the peripheral blood monocytes. Common adverse effects found in clinical trials with mTOR inhibitors were also observed in patients receiving CCI-779 therapy, such as fatigue, neutropenia and thrombocytopenia [ 159 ].

Everolimus has been approved by the FDA for the treatment of pancreatic neuroendocrine tumors, advanced renal cell carcinoma, and advanced breast cancer [ 160 ]. In MM, 17 patients participated in a phase I clinical trial evaluating oral everolimus therapy in RRMM patients, who had received two or more lines of prior treatment. In all patients, no dose-limiting toxicity was observed, leading to a final dose of 10 mg daily. There were eight patients with stable disease, one patient with minor remission, and one patient in partial remission. However, the median time to disease progression was shorter (only 90 days) compared to patients treated with CCI-779. Notably, only one drug-related adverse event was observed, which was pneumonia [ 166 ].

Ghobrial et al. conducted the first clinical trial of the oral TORC1/2 inhibitor TAK-228 in MM patients, as well as patients with non-Hodgkin lymphoma (NHL) or Waldenström's macroglobulinemia (WM). The study evaluated drug safety, tolerability, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and preliminary clinical activity of TAK-228. Ninety-two percent of the patients reported at least one drug-related toxicity, and the most common grade ≥ 3 drug-related adverse events were thrombocytopenia, fatigue and neutropenia. Of the 31 patients with evaluable responses, only one MM patient had a minimal response, while 14 MM patients had stable disease [ 161 ].

CC‐223 is an ATP–competitive inhibitor of mTOR that targets both mTORC1 and mTORC2. CC-223 was shown to be effective in breast cancer, glioma, hepatocellular carcinoma (HCC), non-small cell lung cancer and non-Hodgkin's lymphoma cell lines [ 167 , 168 , 169 ]. Twenty-seven patients with advanced solid tumors and one MM patient were enrolled in a phase I clinical trial with CC-223. Only one partial response was observed in breast cancer, while all other patients experienced either stable disease or disease progression. The most common drug-related adverse events were hyperglycemia, fatigue, and diarrhea. Importantly, an association was observed between a CC‐223 response and the reduction in phosphorylation of AKT, 4E-BP1, and S6 ribosomal protein (S6RP) in stimulated B cells, T cells, and monocytes [ 162 ].

Overall, the above-described clinical studies with mTOR inhibitors as monotherapy showed only low single agent activity in MM, suggesting the necessity of using alternative doses and combination therapies. Twenty patients with RR MM were enrolled in a phase 1 study to evaluate the combination of CCI-779 and BZ, while forty-three patients were enrolled in the phase 2 of this clinical trial. The percentage of patients with a partial response (or better) in the phase 2 study was 33%. In both studies, the most common treatment-related grade 3–4 adverse events were thrombocytopenia, lymphopenia, neutropenia, leukopenia, and anemia [ 163 ]. The combination of everolimus and lenalidomide also showed promising outcomes in a phase I clinical trial in patients with RR myeloma. This drug combination was considered to be relatively safe, with the most common observed grade 3 or 4 adverse events being thrombocytopenia and neutropenia. Of the twenty-six patients included in the evaluation, twenty-three were considered as evaluable responses, with one patient showing a complete response (CR), four patients showing PR, and ten patients achieving MR, accounting for an overall response rate of 65%. Analysis of the plasma samples obtained before and after treatment showed that p-p70S6K was downregulated, and more importantly, responders expressed higher basal levels of mTOR pathway-related proteins compared to non-responders [ 164 ]. Recently, another phase I study of everolimus and bendamustine in patients with RR MM also showed promise, resulting in an 80% overall response rate with only mild adverse events. Eighteen adult patients with RR lymphoid malignancies were eligible. Of the five patients with MM, three patients showed a PR, while one patient achieved a very good partial response (VGPR) [ 165 ].

Conclusions and future perspectives

mTOR has been identified as a central regulator of multiple signaling pathways that work together to integrate growth factor, nutrient, and amino acid signals, thereby modulating the expression and activity of proteins involved in protein synthesis, cell growth and cell survival. While mTOR is a key signaling pathway in MM, most MM studies limit their study to simply demonstrate that different types of inhibitors lead to a reduction in mTOR without further evaluation of the up- or downstream components. Here we aimed to highlight those studies with demonstrated impact on downstream signaling, especially since recent studies using advanced techniques have identified the different components of mTORC1 and mTORC2, contributing to a new perspective on the mechanism of mTOR hyperactivation and the resultant consequences in tumor cells. The recent identification of the novel regulators, such as Tel2 and Tti1, and their function further strengthens the idea that mTOR complexes are intricate assemblies. Future research should further delve into the detailed effects of upstream factors on specific components of the mTOR complexes, aiming to achieve a more profound understanding of its assembly and activation.

While inhibitors targeting the mTOR pathway have achieved significant therapeutic effects in solid tumors (including renal and breast cancer), results of clinical trials testing mTOR inhibitor monotherapies for the treatment of MM have been mostly disappointing. There are several (possible) explanations for these disappointing results. First, the mTOR pathway is a complicated pathway that provides several potential targets, and it remains unclear if one or more targets need(s) to be inhibited in MM and whether these should be simultaneously or rather sequentially. Second, feedback loops contribute to the resistance to mTOR inhibitors. Third, the heterogeneity often observed in MM is likely to make the mTOR activation patterns even more diverse. Finally, high doses inducing adverse effects following treatment with mTOR inhibitors may be due to the critical roles of mTOR in immunity, which is still less understood in MM. Therefore, it would be interesting to investigate mTOR signaling networks in different myeloma tumor clones, as well as in their neighboring cells, including immune cells and BM stromal cells. This will provide crucial mechanistic information to guide the rational development of novel combinations of mTOR inhibitors with chemotherapeutic agents and/or targeted drugs to improve survival of MM patients. Notably, multiple combinations of targeted therapy strategies are suitable only for specific cancer types, as seen with NVP-BEZ235 plus abiraterone acetate (a CYP17 inhibitor), which is primarily used in treating castration-resistant prostate cancer [ 170 , 171 ]. Hence, it will be crucial to identify predictive biomarkers in MM to guide the stratification of patients in clinical trials and identify those likely to benefit the most from treatment with mTOR inhibitors.

Availability of data and materials

No datasets were generated or analysed during the current study.

Abbreviations

Multiple Myeloma

Mammalian target of rapamycin

Bone Marrow

Monoclonal gammopathy of undetermined significance

Proteasome inhibitors

Immunomodulatory drugs

Autologous stem cell transplantation

Overall survival

Chimeric antigen receptor T

MTOR complex 1

MTOR complex 2

Mammalian Lethal with Sec-13 protein 8

DEP-domain containing mTOR-interacting protein

Proline-rich AKT substrate 40 kDa

Regulatory-associated protein of mTOR

Mammalian stress-activated map kinase-interacting protein 1

Rapamycin-insensitive companion of mTOR

Protein observed with rictor

N-terminal domain

RAS-binding domain

Conserved region in the middle

Pleckstrin homology

Telomere maintenance 2

Tel2 interacting protein 1

Phosphatidylinositol-3-kinase

Phosphatidylinositol-3, 4, 5-triphosphate

Phosphoinositide-dependent kinase 1

Protein kinase B

Tuberous sclerosis

GTPase-activating protein

Ubiquitin specific peptidase 4

ADP-ribosylation factor 1

Adenosine 5'-monophosphate-activated protein kinase

Hypoxia inducible factor 1

BCL2-interacting protein 3

DNA damage inducible transcript 4

Insulin receptor substrate 1

G-protein coupled receptors

CAMP-dependent protein kinase

Endoplasmic reticulum

Eukaryotic translation initiation factor 4E-binding protein 1

Ribosomal S6 kinase 1

Eukaryotic translation initiation factor 4E

Programmed cell death protein 4

S6k1 Aly/REF-like substrate

Poly(A)-binding protein

Ribosomal protein S6

PABP-interacting protein 1

Eukaryotic elongation factor 2 kinase

RNA polymerase I/III

5’-Terminal oligopyrimidine

La-related protein 1

Epithelial-mesenchymal transition

Interleukin 6

Insulin-like growth factor-1

Extracellular signal-regulated kinase 1

5-Aminoimidazole-4-carboxamide riboside

Vascular endothelial growth factor

Bone marrow stromal cells

Receptor activator of nuclear factor-κB

RANK Ligand

Monocarboxylate transporters

Pyrroline-5-carboxylate reductase 1

Methionine adenosyltransferase 2α

Phosphatase and tensin homolog deleted from chromosome 10

G9a-like protein

Ras-association domain family

F-box only protein 9

Ubiquitin proteasome system

Immunoglobulin

Dexamethasone

Ribosomal RNA

Nuclear protein 1

Nuclear factor κB

Mitogen-activated protein kinase

Standard of care

Histone deacetylase inhibitor

C-X-C motif chemokine receptor 4

Heat shock protein 90

Insulin-like growth factor 1 receptor

Relapsed/refractory

Partial response

Minimal response

Time to progression

Non-Hodgkin lymphoma

Waldenström’s macroglobulinemia

Maximum tolerated dose

Dose-limiting toxicity

Hepatocellular carcinoma

S6 ribosomal protein

Complete response

Very good partial response

β2 Adrenergic receptor

Ubiquitin C-terminal hydrolase L1

Mitogen-activated protein kinase/ERK kinase

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Acknowledgements

Not applicable.

China scholarship council (No.201906280057)

K.D.V. is a post-doctoral fellow of FWO Vlaanderen (12I0921N)

Vrije Universiteit Brussel (SRP84)

Kom Op Tegen Kanker (ANI365)

International Myeloma Foundation

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Translational Oncology Research Center (TORC) – Team Hematology and Immunology (HEIM), Vrije Universiteit Brussel (VUB), Jette, Belgium

Yanmeng Wang, Niels Vandewalle, Kim De Veirman, Karin Vanderkerken, Eline Menu & Elke De Bruyne

Translational Oncology Research Center (TORC) – Team Hematology and Immunology (HEIM), Universitair Ziekenhuis Brussel (UZ Brussel), Jette, Belgium

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Y.W. and N.V. drafted the manuscript. Y.M. illustrated the figures. E.M., E.D.B and Y.M. conceived and designed the manuscript. E.M., E.D.B, Y.W., K.D.V. and K.V., were responsible for the writing, reviewing and editing. All authors read and approved the final manuscript.

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Wang, Y., Vandewalle, N., De Veirman, K. et al. Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy. Cell Commun Signal 22 , 320 (2024). https://doi.org/10.1186/s12964-024-01699-3

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Received : 13 February 2024

Accepted : 03 June 2024

Published : 11 June 2024

DOI : https://doi.org/10.1186/s12964-024-01699-3

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