Literature Assignment #2 General Instructions

Overview and Schedule:

The assignment has Group work and individual work components. You have been assigned to a Group to help prepare one of six sections of the paper in class. There are five Groups (A, B, C, D and E) for each section of the paper. Each Group will work to answer assigned questions relevant to their own section and create a brief presentation of their answers. Each group will submit two Progress Reports during the four week period leading to the presentation. Your group will then prepare and record a short (5 minute) video presentation using ECHO 360 (more details will follow). These videos will be re-posted in WebCampus. All Groups will peer-review the presentations from other Groups working on the same section, prior to the April 27th class discussion. It is highly recommended that you view presentations of other sections as well. The class discussion will include a selection of the best presentations for each section and should clarify the experimental methods and results, including the sections you did not address in your Group work. Your term paper should be done on your own and should consider the entire article. 26 March 09 April: 02 April: 8:00am, 09 April: 13 April: 16 20 April: 5:00 pm, 20 April: 20 25 April: 27 April: 10:00 pm, 04 May: Discuss the paper within your Group using the Discussion tool First Group Progress Report due through the Assignments tool Use the Sign-Up sheet on WebCampus to reserve studio time for your presentation Second Group Progress Report due through the Assignments tool Prepare and record Group presentations Copy of presentation and Group Participation points are due through the Assignments tool Peer-review other Groups presentations through the Discussion tool Class discussion Individual Term Paper #2 due, submit through the Assignments tool

Instructions:
1. Read the following article: Alvarez-Erviti et al., (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nature Biotechnology 29(4): 341 - 345. You should also download/have available the Supplementary files. These are available as pdfs from the links in the Term Paper #2 module. Read the whole thing, not just the section assigned to your Group. Be prepared to be confused because this paper is very dense and it deals with topics we have not yet encountered in class. But do not be dismayed: it should be challenging but within your ability. 2. Read the Paper #2 Guide. It has useful information and lists all the questions for all sections of the paper.

3. Group work - 30% of your final grade for this assignment. Due April 16 -20, depending on the time you schedule to record your Group presentation. Your preparation for your studio appointment should be complete by April 15 at the latest. a) The Group you are assigned to for this exercise is listed under the Groups tab in your WebCampus page for this course. The Groups are numbered according to the relevant section of the paper. E.g. Groups 4 (AE) will address the questions assigned for Section 4 of the paper. b) New private discussion Groups for Paper #2 are set up in the Discussion area. Only members of your Group and I will have access to it. Use these discussion topics to work out the answers to the questions assigned to your Group with other members of your Group. This discussion is not graded, but will serve as a proof of your contribution to the Group work.

c)

I strongly advise against trying to arrange face-to-face meetings for this assignment. Your predecessors found it almost impossible to schedule a meeting without conflicts. That is why you can use WebCampus tools to work together, virtually.

Progress Reports
d) Two brief Progress Reports need to be completed. One is due on April 02nd, and the other is due on April 13th. The progress reports should be prepared to reflect your groups consensus, although one member of each group will submit the progress report on behalf of the entire group. They will count for a small fraction of your grade. All members in your group will share the same grade. There is a 10%/day late penalty.

Presentation
e) Use the sign-up sheet on homepage of WebCampus to reserve studio time for your presentation. The signup sheet will be made available on Monday, April 09th at 8:00 am. Prior to that date, discuss the preferred date/time for the recording during the week of April 16, but have alternative times in mind - the entire group does not need to be present at the recording. Select a representative from your group to sign up for the studio time. The sign-up will happen on a first come, first serve basis. Please, only one time slot per group. If your group signs up for more than one slot, both entries will be removed and you will have to pick from the remaining slots. f) When your Group has come to a consensus on its answers, work to prepare a short 5-minute presentation in PowerPoint or Prezi (prezi.com). g) Bring your presentation file to the studio (KC 104) at the time of your appointment. You will have 30 minutes to record a five minute presentation, which should be ample time. There will be an assistant there to help you with getting started and saving your recording. h) Each Group has a set number of points corresponding to the number of members of the Group (18 or 24 points for groups of three or four, respectively). These points should reflect the level of your Group participation. The Group members must agree on how these points are to be distributed. E.g. if all members of the Group contribute equally, each should get 6 points. If one member was absent during the entire discussion, his/her points should be distributed among the remaining members. Feel free to discuss point distribution on the discussion board to come to the agreement. This is due on April 25h at 05:00 pm along with a copy of your presentation. i) Submit a copy of your PowerPoint file or a link, if using Prezi , using the Assignment tool by 05:00 pm on April 20th. This is a Group assignment, so only one member of the Group should submit it. In addition, include the participation point distribution with your submission. There is a 10%/day late penalty. 4.

Peer-review 10% of your final grade for this assignment. Due by 10:00 am on April 25nd. By the
evening of April 20th, all submitted Group presentations will be reposted (by Demo Student) under the Group Presentations and Peer-Review: Paper #2 discussion topic in the Discussion area. You are required to individually peer-review the other four Groups presentations that were assigned the same section of the paper. E.g. if you are in Group 4C, you have to evaluate presentations from Group 4A, 4B, 4D and 4E. Each peerreview is worth 2.5 points. To do that, 1. go to the Discussion topic 2. click on the name of the group you are evaluating 3. view the presentation 4. click on the Review this Post button 5. evaluate the submission based on the provided scale 6. explain your grading and compare to your own submission. Additional comments are required for full marks; see the grading section below about this. After you submit your peer-review, the button will change to View All Reviews and you will be able to see other reviews for this post. If you want to see the reviews of your own submission, click on the Review Post button and select This is my group option from the rubric.

You are highly encouraged to read through the answers to other sections to prepare for the class discussion on April 27th. You do not need to peer-review them.

5.

Individual Term Paper #2 - 60 % of the grade. Due May 04th, 10:00 am.
After class on April 27th, prepare a critical analysis of the article (note: not just the portion that your Group worked on). Write your analysis on your own. Briefly summarize the context of the research, experimental methods (leave out buffers and reaction conditions unless they are germane to the Discussion), why experiments were done and the results obtained. Also summarize the conclusions from the research and their significance. Almost all the information that you will need should be in the paper at hand. If necessary, you may need to dig up some other papers to help you. Do not simply offer a precis of the paper. I am most interested in your ability to understand and think critically about the questions being asked and how well they were addressed. Some suggestions to consider while preparing your critical analysis (in no particular order): the context of previous knowledge, the specific questions being addressed, the motivation for the research, the importance of the research and/or results, experimental design, use of technology, data interpretation/appropriateness of the Discussion questions about the subject material that this paper raised in your mind, significance of the article, future experiments that might be inspired by the results. The report should be between 3 and 4 typed pages, double spaced, in 12 point Times New Roman or 11 point Arial font. Use 1" margins. Papers that do not fall within the page limits incur a 50% penalty. Include figures if you wish in addition to the text, but they are not required. Point form notes are not acceptable. You may be critical (every published article probably has at least one mistake), in which case dont hold back, but be careful to justify your criticisms. The report must be submitted through the Assignments tool by 10:00 a.m. on May 04th, 2012. Email a file to me if you have problems with WebCampus. There is a 10%/day late penalty.

Grading:
This assignment is worth 12% of your final grade. It will be marked out of 100 as follows: Group Work (30 points) Content Participation (discussion) Peer Review (10 points) 20 (identical for all members of the Group, assigned by Dr. Tittiger) 10 (varies depending on activity level, assigned by Group members) (2.5 for each review submitted)

Written Paper (60 points) grammar/spelling: 5 points clarity (organization and flow): 5 points contents (understanding and analysis): 50 points The more analysis there is, the higher the value earned for content. A simple precis without an attempt at analysis will earn 30/50 if you appear to understand the paper (obviously <30/50 if you do not). Personal opinions count for a bit more, but to get 50/50 you need to question the methods/ results/ interpretation and/or offer reasonable suggestions for future experiments or alternatives to the Discussion. This is not a

directive to be negative about what you read - if you fully agree then say so and explain why. The point is to weigh the information in the paper and to accept yourself as an authority as to how much you trust it.

Here are the questions that your group needs to address:

Group 1
Introduce the motivation/premise of the paper (first paragraph). Explain Figure 1a. What three criteria do the researchers hope to satisfy in this paper in order to make siRNA-based therapies feasible?

Group 2
Explain (summarize Figure 1, Supplementary Figure 1, and Supplementary Figure 2 Which of the three criteria is being addressed in these figures? How were the exosomes given the ability to target neural or muscle cells? Why was the control experiment in Supplementary Figure 2b necessary?

Group 3
Explain (summarize) Supplementary Figure 3, Supplementary Figure 4a, b. How are siRNAs loaded into the exosomes? At this point, why does the sequence/identity of the siRNA not matter?

Group 4
Explain (summarize) Supplementary Figure 4c, d and Figure 2 How does the experiment presented Supplementary Figure 4c, d extend the findings from Supplementary Figure 4a, b? Explain the role of BACE1 in Alzheimers disease Why were these experiments necessary (how are they controls in the context of the main point of the paper)?

Group 5
Explain Supplementary Figure 5. Why was this experiment necessary?

Group 6
Explain (summarize) Figure 3a d, Supplementary Figure 6 and Supplementary Figure 7 experiments targeting GAPDH How would GAPDH knockdown allow the researchers to investigate the specificity of their targeting strategy? Why would the researchers want to investigate repeated doses?

Group 7
Explain (summarize) Figure 3e h, Supplementary Figure 6c experiments targeting BACE1 Note the controls in this section How does Figure 3h support their claim that their system not only works, but is therapeutically useful? Note the difference between RVG exosomes and RVG-9R.

Group 8
Explain Supplementary Table 1 Briefly explain the significance of the immune response to RVG-9R. Outline the broad conclusions of the paper.