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The Washington Research Foundation Fellowship

Mark Lisowski, Biochemistry and Biology, 2010-11 WRFF/Space Grant

Mark Likowski photoGrowing up I always had endless questions about biology, because everything from moss to the human body seemed incredibly complex and fascinating to me. Now, after years of terrific science classes and research experiences, I have more questions than ever! One topic that particularly interests me is diabetes, because it has tremendous effects on people worldwide, and because the etiology of this disease is still not fully understood.  I currently work in the laboratory of Dr. Ian Sweet, whose research focuses on advancing our knowledge of the causes, effects, and possible treatments for diabetes. My present project aims to elucidate new components of the intracellular pathways that regulate the secretion of insulin, a hormone that is critically involved in regulating the levels of glucose in our blood.

Being involved in research has taught me more than I could have imagined. It has given me the opportunity to work with experienced scientists and to learn cutting-edge techniques. And of course it has expanded my base of knowledge in biochemistry, physics, and biology. Research has further solidified my interest in human biology and medicine, and so after graduating in the spring of this year I plan to apply to MD/PhD programs. I would like to thank the Mary Gates Endowment, Washington NASA Space Grant Consortium, and the Washington Research Foundation for supporting the research that has so profoundly shaped and enriched my undergraduate experience.

Mentor: Ian Sweet, Medicine

Project Title: Identification and Characterization of Calcium-Sensitive Processes that Mediate Insulin Secretion

Abstract: Dysfunction of pancreatic 0-cells leading to inadequate insulin secretion is a major determinant in the development of diabetes. A detailed understanding of the intracellular processes that mediate insulin secretion is therefore critical to advancing diabetes research, and may provide the foundation for new or improved diabetic therapies. Studies from the lab of Dr. Ian Sweet have shown that both metabolic stimulation and calcium influx are required for insulin secretion, and that insulin secretion is accompanied by a high rate of energy usage. This has led to the hypothesis that a highly energetic, calcium and metabolism -sensitive process (named the CMCP) mediates insulin secretion. The focus of my research is to identify the proteins that are involved in the CMCP and to further characterize the role of the CMCP in insulin secretion. Previous data has supported the existence of the CMCP in a P-cell line (INS-1 832-13), and so this cell line will be used to identify CMCP proteins. Collaborating scientists will first isolate and identify possible CMCP proteins. I will then determine whether these proteins are involved in the CMCP by inhibiting or stimulating the proteins and observing the resulting response of intracellular calcium levels, oxygen consumption, and insulin secretion. Measurements of these parameters will be carried out using a sophisticated flow-culture imaging system. I have additionally optimized this system so that measurements can be made for a single pancreatic islet (about 1,000 cells), allowing me to observe small changes in CMCP activity that would not be possible to resolve if multiple islets were used.