University of California, San Francisco (UCSF)

A Mechanistic Study of Infectious Proteins

Research Area

Grant Type



Multiple neurodegenerative diseases are caused by the accumulation of protein in the brain. Two of these disorders, Alzheimer’s and prion diseases form protein aggregates that can be infectious. The protein aggregates are mainly composed of a single protein, either A-beta (Alzheimer’s) or PrP (prion diseases). These proteins are both expressed naturally in healthy people throughout their lives, but the misfolding of either protein causes aggregation and death of brain tissue. Understanding this misfolding mechanism is very important because experimental results suggest that it is not simple, random, aggregation. It seems to occur in an ordered process that effects the host in a remarkably specific manner.

The overall goal of my research is to develop a mechanistic model for the propagation of misfolded protein within the Alzheimer’s and prion diseases. Understanding this process is key to stopping the progression of the disease, and also understanding how the fidelity of strains is maintained without DNA and/or RNA. I am using the prions of mice and hamsters as my model and focusing on two specific objectives. 1) Establishing the minimum number of components necessary for the production of infectious proteins in a cell-free environment, and 2) Investigate the mechanism of the prion propagation in vitro.