Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Medical Biophysics

Supervisor

Dr. Savita Dhanvantari

Abstract

The pathology of Type I Diabetes mellitus is characterized by a significant or complete ablation of the insulin secreting p-cell population of the pancreas. The loss of P-cell mass is mediated by apoptosis and it has been shown that the enzyme caspase-3 plays a pivotal role in the execution of apoptosis. Imaging of caspase-3 in live p-cells can provide a novel tool for exploring disease progression in Type 1 diabetes. In this thesis I have validated the use of a bioluminescent caspase-3 reporter for monitoring apoptosis induced by pro- inflammatory cytokines in a clonal rat derived P-cell line (INS-1/832/13). I have shown that the caspase-3 reporter construct and imaging strategy can detect changes in caspase-3 activity with high sensitivity and temporal resolution, and that caspase-3 activity induced by cytokines is transient in nature.

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