Structure & Function of Biomolecules - Project Work

Along the Structure & Function of Biomolecules course, you will get the opportunity to study a specific topic related to the course more in-depth in the form of a project work. The work will be conducted in groups of four students, and include the search for related information in scientific journals, books and on the internet, summarize your most important findings in a written report and finally present your work orally to the other students and teachers. Once you have formed a group, you select a topic based on the list below. Since several groups may select the same topic, please also select two backup choices. Two groups will be allowed to have the same topic. Once the topics have been divided between the groups, you will be informed of your topic and each group will be given a mentor to assist them throughout the project work. Below you can find a table describing the different checkpoints in the project work and the dates for when each part of the work should be finished. Further down you can also find a description of what is expected from you when carrying out the different tasks. First you need to form groups and select your projects. Please send an e-mail to Anna Jansson (anna.jansson@icm.uu.se) at the latest Tuesday November 9, 17:00, containing the following information: Complete names of all members in your group e-mail address that you check frequently to each group member Three project topics in the order that you prefer them If you have not found a group by this time, send an e-mail and tell us, so that we can arrange a group for you. The topics will then be distributed between the groups, and before 10:00 on Wednesday November 10, you will receive an e-mail informing you on which topic you have received, which group you will be collaborating with in exchanging feedback as well as which mentor you have been appointed.

Task
Project plan

what should be done?

Write project plan, version one. Feedback from mentor on project plan. Final project plan should be approved.

by when?
Friday 12/11 17:00 Monday 15/11 17:00 Wednesday 17/11 17:00 Wednesday 1/12 18:00 Friday 3/12 12:00 Monday 6/12 17:00 Wednesday 8/12 17:00

Written report

Completed first draft of written report. Feedback on written report by mentor. Incorporate suggestions from mentor and send this version to both the mentor and opposing group. Give constructive feedback on the written report that you have received from your opposing group. Then send a copy of the report including your feedback to both your opposing group and your mentor. Incorporate the feedback from the opposing group into your written report, and send to your mentor. Second round of feedback from your mentor. Hand in final version of report to your mentor. Your mentor will make sure that the opposing group receives a copy of the final report.

Thursday 9/12 18:00 Monday 13/12 17:00 Wednesday 15/12 10:00 Wednesday 15/12 16:00 Wednesday 15/12 17:00 Thursday 16/12 10:15-15:00

Presentation

Go though oral presentation with your mentor. Send final version of your presentation to your mentor. Present your work to your fellow students, the mentors and teachers. Give oral feedback on the written report and the oral presentation of your opposing group.

Project plan The project plan should about one A4-page (absolute maximum two pages) and must include: Title of the project Names of group members Aim of the project or question(s) it tries to answer (1 or 2 sentences) Brief background of the subject of your project Plan of attack (how are you going to achieve the aim?)

Report The written report should be 4-5 A4-pages, but not longer than 5 pages. It should contain similar information as the project plan, but also more in-depth information and an overview of the results obtained, a discussion of these results and their interpretation, a set of conclusions or recommendations, and a list of literature references. A few key figures or tables can be included. The report should be written in Times New Roman 12pt, single line space. Presentation The presentation on the final day should preferably be done PowerPoint saved in ppt-format. Make sure you captivate your audience (with blinding science, that is - not with special effects)! The presentation should not be longer than 15 minutes (to leave 5 minutes for discussion and feedback from opponents). This means that your presentation should probably have ~10-20 slides. The seminar day with the presentations is mandatory! Yes, the whole day! You are not allowed to bring personal laptops to the seminar day. You are expected to give your full attention to the presenting group at all times during the day, be active in discussions and ask questions to the group presenting. Feedback on other groups work You are expected to give constructive feedback on the written report and oral presentation of another group. When you evaluate the work, try to answer the following questions. Is the works clearly described? Are the aim, results and conclusions presented in a clear and convincing way? Is the language correct grammatically? What could be done different to improve the work? During the project you will get a chance to give written feedback to another group. You will get a second chance to read the same report just before the oral presentations. On the day of the presentations you will be expected to give short but well thought through feedback on both the written report and the oral presentation of your opponent group. Assessment of you work The quality of the written report and your oral presentation are very important, but you will also be assessed on other things. These are: How well you perform as a group, your ability to give feedback on another groups work, and how well you incorporated feedback that you received both from your mentor and from the other group into your report, and how well you kept all your deadlines, and how you planed the work. Grading and bonus points You must obtain a pass on the project work to be able to complete the course. You have passed when your mentor tells you so. You might need to do additional work on your report that is not included in the time plan. However, there is also a possibility for you to earn two bonus points for the exam if you complete the project with distinction. The focus for earning the bonus points will be the oral presentation, but all parts of the project will be considered.

Important! You are most welcome to use any material to find information for your project. However, two things are crucial 1. You must reference any source you have used for your report. 2. The written text should be your own words. To copy text or use identical wording is plagiarism, which is strictly forbidden, and will lead to that you fail this part of the course.

Suggested project - Case studies

Objective: to study a subject in detail, with special emphasis on its structural biology aspects. Description: There are many topics in the area of structural biology that are fascinating in themselves but for which there is no time in the course to study them in great detail. In addition, there are many issues in science, medicine and biotechnology where structural studies of biomacromolecules play or have played an important role. In these case studies, you select a topic from the list below and study that in more detail. Find out: what the medical or scientific or technological importance of the topic is which biomolecules are involved what role they play for which of them structures are known (or could be predicted) how the molecules of known structure work at the atomic level what studies have been done to alter their behaviour (mutations, inhibitors, ...) etc. The precise scope of your project and the questions you would like to answer depend stongly on the topic that you choose to study, of course. In some cases, it may be opportune to do some homology modelling to get a structural hypothesis for a protein whose structure is not yet known. In others, you may need to do sequence analysis (database searches or multiple alignments). In all cases, you will need to look at structures you get from the PDB, determine their fold, active site residues, interaction surfaces, etc. Snake toxins. Snake venoms are complicated mixtures of toxins. What do they contain? How do they work (physiologically and at the molecular level)? What structures are known and what can they tell you? Which molecules do they interact with? Are any toxin-target complex structures known? p53 and cancer. What is the normal role of this protein and how is it connected with the development of cancer? What have all the structural studies of this protein taught us about its properties and the possibilities for a cure? Antibiotics What biomolecules are targeted by antibiotics? Which structures are known? How do antibiotics work at the molecular level? Increasing resistance to current antibiotics is a major health threat. Why is this? Are new antibiotics being developed? How do they differ from the current ones?

Evolution of tRNA synthetases The two classes of tRNA synthetases are specific for amino acids in a way that appears symmetric. A hypothesis for their evolution has been presented in TIBS 26 (2001) 591-596. Use available structures to present and discuss this hypothesis! Ion and ligand channels There are many different types of channel and structures are known for quite a few of these. Select 2-4 different types of channel (e.g., sodium, potassium, mechanosensitive, ...) and study their architecture and how the structure explains how the appropriate ion or ligand can be transported. Compare the structures as well. Explain why some channels are highly specific (e.g., potassium channel) while others are promiscuous (e.g., mechanosensitive channel). Clathrin This is a prime example of form following function. What does clathrin do? What is known about its structure, symmetry and assembly? What role do the various adaptor proteins play? What is known about their structures? Allergies The PDB contains many structures with different allergens but very few with IgE antibodyallergen complex. What is known about the cause of allergies and what information is lacking? There was also one structure published in November 2007 including IgE and an allergen for bovine milk hypersensitivity. What is new about this structure? Influenza One of the first applications of structure-based drug design involved influenza. Which proteins are involved? What drugs are on the market? How were they developed? How do they work? Could they play a role in the control of flu pandemics? AIDS How does the disease work at the molecular level? Which proteins are involved? What do they look like? What is their mechanism? Which drugs have been developed? How do they work? Why is resistance a problem? Cellulose degradation Which industrial applications do cellulose degradation have? Which enzymes are involved? How are they classified? How do they work? How can they be improved? Caspases - the executioners of apoptosis Study the phenomenon of programmed cell death (apoptosis). What role do caspases play? How are they regulated? Each student selects a different caspase structure and studies the architecture, mechanism, specificity, role in apoptosis, etc. Chemical warfare Which agents have been developed? Which molecules do they interact with? How do they work (physiologically and at the molecular level)? Are any relevant structures known? What do they tell us?

Cytochrome P450 enzymes - detoxification and synthesis How do these enzymes help us stay healthy? How do they affect the effect of medication we take? Can they harm us? What chemical reaction do they carry out? What useful compounds do they help synthesize? Pick a few important members of this family (such as CYP3A4 and P450cam; not necessarily human enzymes). What does the structure look like? What does the active site look like? What do the structures teach us about the mechanism? Ricin and the umbrella murder "On 7 September 1978 the Bulgarian dissident Georgi Markov was stabbed in the leg in public on Waterloo Bridge in the middle of London by a man using a weapon built into an umbrella. The weapon embedded a small pellet in Markov's leg that contained ricin. Markov died four days later." (Source: Wikipedia) Study the structure, function and toxicology of ricin. How does it work? Find similarities and differences with various bacterial toxins (cholera toxin, diphtheria toxin, enterotoxin, ...). Could ricin have medicinal applications? Telomerases The Nobel Prize in Physiology and Medicine in 2009 was awarded three scientists for their studies of telomerase. What is the role of telomerases in the cell, and what is known about the structure and function of the enzyme? Caspases - the executioners of apoptosis Study the phenomenon of programmed cell death (apoptosis). What role do caspases play? How are they regulated? Each student selects a different caspase structure and studies the architecture, mechanism, specificity, role in apoptosis, etc. Project Green Light Green Fluorescent Protein (GFP) is in the news due to the 2008 Nobel Prize in chemistry. Describe the use of this protein in genetic engineering and in biosensing. Study the structure and function of the protein and the chromophore. GTPases in translation Elongation factor G is a GTPase that catalyzes two steps in the translation cycle: translocation and ribosome disassembly (good translation review is Schmeing & Ramakrishnan (2009) Nature 461:1234-42). In human mitochondria, it has recently been found that these two tasks are catalyzed by two different proteins (Tsuboi et al. (2009), Molecular Cell 35(4):502-10). How are these two proteins different? Compare the sequences of human mitochondrial elongation factor G and ribosome-releasing factor 2 and analyze the differences based on the available structures of bacterial EF-G and the complex of EF-G with the bacterial ribosome. Can the differences suggest why these two proteins perform different tasks? CRISPR - a bacterial immune system It has recently been discovered that some bacteria and all archea have an inheritable RNAbased immune system that can protect them against phage infection (reviewed by van der Oost et al (2009), Trends in Biochemical Sciences 34( 8):401-407). How does this work? What is structurally known about this system, and what do the available structures explain?