Team Leader
Jadon Sitton
Texas A&M University College Station
BCBP
jadon.sitton75@tamu.edu
Project Type
Research
Who Can Join
Undergraduate Students
Project Description
Type 2 diabetes (T2D) is characterized by irreversible insulin resistance and chronic hyperglycemia. A hallmark of this pathology is the aggregation of islet amyloid polypeptide (IAPP), a small peptide-hormone produced in the pancreas. Aggregation of this peptide leads to the formation of amyloid oligomers and fibrils in the pancreatic islets. These oligomers and fibrils propagate through the pancreas and are highly cytotoxic to the insulin producing β cells. The death of these cells leads to reduced insulin production and heightened hyperglycemia, effectively accelerating the pathogenesis of T2D and its co-morbidities. Further, T2D pathology has been more recently characterized by significant changes in the lipid composition of β cell membranes. However, it is not well understood whether these pathological changes in β cell membrane composition influence the aggregation of IAPP. My preliminary results indicate that the saturated phospholipid membranes accelerate the aggregation of IAPP, simultaneously influencing the cytotoxic effects of these aggregates. The proposed study aims to expand on these findings by determining the influence of lipids on the onset and progression of T2D-related IAPP amyloidosis. The first aim will focus on the biophysical characterization of IAPP aggregation in the presence of key cell-membrane lipids. This aim will reveal the relationship between the morphology, secondary structure, and cytotoxicity of IAPP aggregates. The second aim will elucidate the effects of dietary lipids on the pathogenesis of T2D-related IAPP amyloidosis through a diseased β cell model. Finally, the third aim will demonstrate the importance of lipid-protein interactions in the design of therapeutics against IAPP aggregation. This study will fill major gaps in current knowledge of IAPP aggregation in the context of T2D pathology, simultaneously informing future therapeutic strategies for T2D-related IAPP amyloidosis.
Team Needs
Highly motivated undergraduate students who are interested in biochemistry and molecular biology. Students should be responsible with good time management skills, have a basic understanding of presentation skills, and have a growth mindset.
Special Opportunities
Opportunities to present work at conferences and earn authorship on academic publications.