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Phd Defense by Zachery Deckner

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In partial fulfillment of the requirements for the degree of

 

Doctor of Philosophy in Biology

In the

School of Biological Sciences

 

Zachery Deckner

 

Will defend his dissertation

 

YEast model for seeding and cross-seeding of protein aggregation in proteopathies

 

Thursday, July 8th, 2021

11:00 AM

 

https://bluejeans.com/607594679/4139

Meeting ID: 607 594 679

 

 Thesis Advisor:

Yury Chernoff, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

 

Committee Members:

Kirill Lobachev, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

 

Francesca Storici, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

 

Nicholas Seyfried, Ph.D.

Department of Biochemistry

Emory University

 

Matthew Torres, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

 

ABSTRACT: A variety of human diseases, including Alzheimer’s disease (AD) and tauopathies, are associated with the accumulation of misfolded protein aggregates. These protein aggregates are composed of amyloids, protein aggregates that contain highly ordered b-sheet structures that are very stable and quite insoluble. Yeast are also plagued by amyloids. In yeast, amyloids manifest themselves as infectious proteins, termed yeast “prions” that are heritable via the cytoplasm. While not necessarily considered a disease in yeast, our understanding in how and why yeast prions form and propagate have led to insights that have translated to our understanding of proteins associated with human diseases.  My thesis work has employed yeast as a model system to understand the specific sequence elements as well as other cellular factors that contribute to protein misfolding of proteins associated with disease in humans, including Ab42, MAPT, and U1-70k, all of which are associated with AD. Firstly, I have shown that the Aβ-based prion in yeast is controlled by the Ab42 peptide. I also used this prion system to study Ab42 isolated from patients suffering from AD to demonstrate that Ab42 is capable of forming prion variants. Secondly, using high expression plasmids I have shown that MAPT, the repeat domain of MAPT, and the C-terminal domain of U1-70k are capable of forming detergent-resistant aggregates in yeast, a characteristic of amyloids. Lastly, I have used a novel yeast assay to study the nucleation capabilities of protein peptides that have recently been associated with diseases, as well as use it as a high-throughput screening platform to test newly synthesized compounds to determine if they can prevent the initial nucleation of Ab, the triggering event in AD. Overall, this work provides new information on the molecular mechanisms that drive protein aggregation.

 

 

 

 

Status

  • Workflow Status:Published
  • Created By:Tatianna Richardson
  • Created:07/07/2021
  • Modified By:Tatianna Richardson
  • Modified:07/07/2021

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