Date of Award

6-2022

Degree Type

Honors College Thesis

Academic Program

Biological Sciences BS

Department

Biological Sciences

First Advisor

Vijay Rangachari, Ph.D.

Second Advisor

Bernd Schroeder, Ph.D.

Third Advisor

Sabine Heinhorst, Ph.D.

Advisor Department

Chemistry and Biochemistry

Abstract

One of the main causes of neurodegenerative diseases is aggregation of amyloid proteins that are toxic to the neurons. Proteins like amyloid-β (Aβ) and α-syneuclein (α-syn) form hallmark aggregate lesions that contribute to pathological processes in the brain in Alzheimer and Parkinson’s patients, respectively. Recent ground-breaking studies have suggested a link between the microbiota of the gut and neurodegenerative diseases, called the “gut-brain axis.” It has been long known that the protein, CsgA found in many enteric bacteria, forms amyloid fibers of its own called Curli. Curli fibrils are a structural component of bacterial colonies and maintain the integrity of biofilms, making CsgA a “functional amyloid protein.” In this study, the hypothesis that CsgA and Aβ interact directly with one another to support the suggestion of the gut-brain axis is investigated. To do so, a plasmid containing CsgA is recombinantly expressed in E. coli cells and then purified in large scales for further testing of its interactions in-vitro. Various biophysical methods were used to isolate the CsgA protein in pure form. Once isolated, the interactions of CsgA with Aβ and other extracellular components reveal that CsgA inhibits the aggregation of Aβ, but Aβ seems to have no effect on the aggregation of CsgA. CsgA aggregation was also observed to be unaffected by the presence of NaCl.

Keywords: protein aggregation, neurodegenerative disease, brain-gut axis, amyloid-β, Curli

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