Poster Abstract

January 7, 2011

Investigation of the role of Histidine 95,110Y in ?-cleavage in Mouse PrPc

Mario Gallardo
Mario Gallardo
MARC U*STAR Fellow Summer Research Student

Abstract: Prion diseases occur when a conformational conversion in cellular Prion Protein, PrPc produces a proteinase-resistant form, PrPsc which is primarily localized to the brain. Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob, and Scrapie are all examples of such neurodegenerative diseases. The conversion from the normal PrPc to the infectious form is not clear, nor is the physiological role of PrPc. It has been hypothesized that the PrPc plays a role in copper homeostasis. PrPc coordinates copper within the octarepeat region. Component 1 dominates at low Cu2+ and coordinates one Cu2+ to each octarepeat, while component 3 dominates at high occupancy and coordinates 3 to 4 octarepeats to one Cu2+. In the presence of reactive oxidative species (ROS) and Cu2+, ?-cleavage occurs close to or within this region. LCMS was performed on mouse PrPc mutants in order to understand which mutants were created to understand which components are involved in ?-cleavage.

B-Cell Receptor Gene Rearrangement Frequency as a Measurement of Receptor Editing in Autoimmunity
Trinidad Cisneros
MARC U*Star Fellow Summer Research Student, Harvard University

B-cell receptor editing is an important mechanism in tolerizing B cells and preventing autoimmunity. The objective of this study was to determine the frequency of B-cell receptor editing in patients with autoimmune diseases and compared to normal controls. Given that defective B-cell receptor editing may have a role in the pathogenesis of B-cell associated autoimmunity we hypothesized that at least a subset of patients with autoimmune disorders will have distinct differences in the frequency of receptor rearrangement compared to normal controls. Genomic DNA was isolated from purified B-cells of normal controls and patients with autoimmune disorders. Real-time quantitative PCR (RTq-PCR) was utilized to assess the frequency of B-cell light chain rearrangements. The results indicate that patients with autoimmunity may have higher levels of receptor editing compared to controls.

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