Ph.D. Proposal Presentation
2:00 PM, Friday, October 24, 2014
U.A. Whitaker 1214

Advisor:

Andreas S. Bommarius, Ph.D. (Georgia Institute of Technology)

Co-Advisors:
Sven H. Behrens, Ph.D. (Georgia Institute of Technology) Yury O. Chernoff,
Ph.D. (Georgia Institute of Technology)

Committee:
M. G. Fin, Ph.D. (Georgia Institute of Technology)
Julie A. Champion, Ph.D. (Georgia Institute of Technology)

Studies on Amyloid Aggregation and Cross-Species Prion Transmission

Amyloids are an important class of proteins because of their involvement in
a number of neurodegenerative diseases such as Alzheimer’s disease,
Parkinson’s disease, and Huntington’s disease. Notably, these proteins have
a tendency to acquire a stable alternate conformation rich in beta-sheets
and associate with each other to form fibrous ordered aggregates. Due to
their unique properties and involvement in a number of fatal diseases there
is a lot of interest in studying this class of proteins. Another
characteristic of amyloidogenic proteins is that a given protein may adopt
many distinct conformations, known as “variants” or “strains”. Once formed,
a strain is efficiently reproduced under the same conditions on addition of
the same prion protein. On the other hand, cross species transmission of
prions is less efficient due to a “species barrier” which prevents the
transmission of the prion state between prion proteins from different
species with divergent sequences. The molecular basis of prion transmission
and mechanisms of prion strain formation are not yet fully understood.

The overall objective of this thesis is to study how ion specificity affects
the mechanisms of aggregation and cross-species transmission of
amyloidogenic proteins. Amyloid aggregation process will be studied using
the NM fragment of Sup35 and Amyloid beta 1-42 peptide as model systems to
understand the aggregation mechanism and study the effect of environmental
factors on aggregation kinetics. The insights gained from this study will
allow extension of these concepts to other mammalian systems and will be
useful for developing new methods for preventing amyloid aggregation.