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The Levinson Emerging Scholars Program
Jonathan Keller - Biochemistry
I first became interested in protein research during an honors biology seminar, studying the Ice Worm and the various adaptations that allow it to thrive in frozen environments. I was particularly intrigued by the protein modifications suited to low temperatures, structural variations that enhanced functionality in sub-zero climates. I was interested in further pursuing protein research, especially as it related to the medical field, and began working in the lab of Dr. Rachel Klevit. The Klevit Lab studies the breast cancer susceptibility protein BRCA1 using high resolution structural biology techniques such as Nuclear Magnetic Resonance (NMR). The research offers powerful insight into the structural and functional properties of BRCA1 and has profound implications in developing far more precise and effective cancer therapy.
My hope is to attend medical school and eventually pursue a career that incorporates both patient care and biomedical research. I am especially interested in pursuing cancer research, as the field is still just beginning to understand the complex biochemical interactions involved in such a wide array of pathologies. My current experiences in the Klevit lab studying BRCA1 are invaluable to that development. The knowledge and skills I have gained since beginning research are fascinating and have enhanced my understanding of biochemistry through intensified, hands-on application.
Mentor: Rachel E. Klevit, Biochemistry
Project Title: BRCA1-mediated ubiquitination
Abstract: The breast cancer susceptibility gene, BRCA1, encodes a crucial tumor suppressor protein involved in multiple DNA damage repair pathways. One of its most important functions is ubiquitin ligase activity, in which BRCA1 facilitates the transfer of the small protein ubiquitin to other protein substrates. The ubiquitin acts as a molecular tag, important for marking substrates in many cellular processes such as proteolysis, cell signaling, and DNA repair. The loss of ubiquitin ligase activity when BRCA1 contains cancer-associated mutations suggests an important role for this function in tumor suppression capacity. The various steps of ubiquitination also require adaptor proteins in addition to BRCA1 to successfully mediate ubiquitin transfer. The process by which the proteins interact, and why mechanistically the adaptors are necessary for transfer, is still unknown. The use of high resolution structural biology techniques, such as Nuclear Magnetic Resonance (NMR), offers powerful insight into the three dimensional characteristics of BRCA1-protein complexes. Structural elucidation will furthermore provide insight into the physical relationship and function of each interacting component, and expectantly lead to more precise treatment possibilities for breast cancer, the second most common cause of cancer related death in women.