MbShea@PWP@English@UMCP

ABSTRACT: Type 2 diabetes (T2D) is a chronic disease characterized by hyperglycemia and hyperinsulinemia due to insulin resistance. Historically, T2D has been ascribed to risk factors such as inactivity, poor diet, and obesity. More recent research indicates that immunological components likely contribute to the pathogenesis of the disease. B-lymphocytes have been shown to play a critical role in initiating autoimmunity in the context of obesity-associated insulin resistance. Preliminary findings suggest that dysregulation of B-lymphocyte lipid metabolism triggers non-specific B-lymphocyte activation. I propose that self-reactive B-lymphocyte recruitment to adipose tissues triggers autoantibody production, the development of an autoimmune pathology, and subsequent insulin resistance. To test this hypothesis, I will use immunohistochemical techniques to determine how B cell-specific triglyceride accumulation affects the number of total B cells, regulatory B cells, and plasma cells in adipose tissues using a B cell-specific knockout mouse model. I will also use ELISA and immunofluorescence microscopy to study autoantibody production, and a tissue array to identify autoantibody targets. Lastly, I will examine immune pathology in the kidney and adipose tissues using immunofluorescence microscopy. Delineation of how B-lymphocyte autoimmunity contributes to T2D leads to better understanding of its causes and novel approaches for its prevention.

READER’S PROFILE: I am writing a research proposal to an interdisciplinary panel of UMD faculty that sit on the Howard Hughes proposal review committee. As such, I imagine an exacting, critical audience. My proposal will be in a competitive situation, as it is competing against other projects for funding from the Howard Hughes Medical Institute.

READER’S RESPONSE: I imagine that the proposal review committee will be curious about more of the background and significance of my research. They will also be wondering how I specifically aim to test my hypothesis, and how feasible the project actually is (in terms of if I have received any preliminary research results).

VOICE: I am writing for a technical audience, so I will be writing with a distant/objective tone, without humor. The proposal will be written in 3rd person.

CITATION: I will follow a formal citation style. I will use superscripts to provide in-text citations within my research proposal. A bibliography will also be included with references listed in consecutive order.

E -- nicely designed experiment. By the way, did you know that we really have more than Type 1 and Type 2 categories? Most seem to have a immune component, as you rightly describe. Also, European systems use different threshold categories to diagnose these conditions.