Bi 1 2009: Developing a cure for AIDS -- Engineering Immunity or another idea

For extra credit (up to 20 points to be applied to your score on the final), we ask that you submit an idea for how to prevent or cure HIV infection. You will receive credit for any well-thought out and reasonable idea, even if it wouldn’t work for reasons that are beyond what the scope of this class. If you wish to use an “Engineering Immunity” gene therapy approach (as discussed in class), please follow the guidelines below for describing your idea. If you have a different sort of idea, please follow the guidelines described for a Grand Challenges Exploration grant: go to

http://www.gcgh.org/Explorations/Pages/ApplicationInstructions.aspx

and click on “Create New Vaccines for Diarrhea, HIV, Malaria, Pneumonia, and TB” (right side of screen). As you will see by reading this website, the Bill and Melinda Gates Foundation is inviting anyone and everyone (i.e., you don’t have to be an established scientist) to submit short (maximum of two pages) proposals describing new ideas that are “off the beaten track” and “daring in premise”. Applicants chosen by the Gates Foundation for funding will receive $100,000 to carry out the research, with the possibility of more funding if the initial results look promising. The deadline for Round 3 of Grant Challenges Explorations is May 28, 2009, but Round 4 submissions will likely be due later on in the fall, so you could submit your idea then. If anyone is interested in submitting his/her idea for Round 4, we will be happy to discuss it further with you and/or help you write the actual proposal. If you are chosen for funding, we will find a laboratory at Caltech where you can conduct your research. If you are not chosen for funding, but are committed to trying your idea, we will help you find a way to test your idea in a lab at Caltech or elsewhere as a SURF project. Good luck!

Guidelines for a proposal based on an Engineering Immunity gene therapy approach

In lecture you have learned (or will learn about in the Vaccines lectures [23 & 24] near the end of the term) about a gene therapy method to "Engineer Immunity" against HIV by providing a person with the means to make a life-long supply of antibodies or antibody-like proteins that neutralize HIV. Your task is to design a protein (or collection of proteins that function together) that neutralizes HIV and whose gene or genes can be delivered using a lentiviral vector. Your protein(s) can include antibody components, but you are not constrained to designs based on antibodies. The only designs we will not accept are molecules already shown on one of the Engineering Immunity slides. Your answer must address the following:

• The molecule and its mechanism of action (a schematic diagram of the molecule with labels is probably the easiest way to describe it). Be creative in your design—any reasonable design will be accepted even if the resulting protein is difficult to produce for reasons beyond the scope of what you learned in class.
• The cell type that will initially receive the instructions for synthesizing the protein and why you have chosen this cell type.
• The specific target or targets of the molecule (the target(s) don’t necessarily have to be restricted to components of the virus) and why you have selected this target(s). Be aware that the target must be accessible to your designed protein.
• The step(s) in the HIV life cycle that the molecule inhibits.
• Why inhibiting this step (or these steps) might lead to the prevention of an initial infection or the elimination of an infection that is already present.
• One advantage and one disadvantage of your design.

If any student wishes to make and test his/her designed construct, see Pamela.

This extra credit assignment is due by Friday, June 12th at 5:00 PM.
Please email them directly to Professor Bjorkman (bjorkman@caltech.edu) in Microsoft Word (.doc) format (not PDF).