Short term:

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)

 

Longer term:

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?