Read with caution!
This post was written during early stages of trying to understand a complex scientific problem, and we didn't get everything right. The original author no longer endorses the content of this post. It is being left online for historical reasons, but read at your own risk.
1. Known ffi sufferers who had had their tonsils and/or spleen out? (s)
2. Pursue data on human FFI sufferers (e)
3. Learn more about david baker @ uw-seattle – ab initio protein structure prediction (e)
rosetta algorithm – has won several critical assessment of structure prediction competitions/ CASP
rosetta@home – you can work on predicting protein structure at home
4. Schedule meeting with contact at the Lindquist lab (3)
5. Register a new email address and put it on the web page (e – done)
6. Watch videos from annual CJD conference about update on doxycycline trials in Europe (s)
7. Learn more about attending annual CJD conference (s)
8. Find info about PrP(Sc) being proteinase-resistant/ detergent-insoluble and post to site (s)
Potential experiments related to follicular dendritic cells in spleen:
Experiment 1: knock PrP out of follicular dendritic cells in spleen (which prevents vCJD) but
then introduce PrPsC into brain and see if mice still get it
Experiment 2: see if mice with spleen and tonsils out are susceptible to PrPSc/FFI
Potential fundable research topic for a grad student:
Obtain a structure of the misfolded prion protein
Solve the structure of both versions of the protein in both states
Get an idea of the thermodynamic difference between the wildtype and mutant protein
and whether chaperones interact with them
To think more about:
Nature of GPI anchor
Structure of PrP protein; proximity of mutation at D178N, disulfide bond at Cys179 and Cys214, and glycosylation at Asn181 and Asn197
Does this disulfide bond change oxidation/reduction status in the event of misfolding?
What’s known about the redox state of the protein and its ability to convert?