MIT Department: Biological Engineering
Undergraduate Institution: North Dakota State University
Faculty Mentor: John Essigmann
Research Supervisor: Bogdan Fedeles
I am a senior at North Dakota State University, where I study Biochemistry with minors in Mathematics and French. Currently, I research metabolic pathways of cancer in a research lab on campus. I intend to further my education in a Ph. D. program after completing my undergraduate degree, and work in a research lab. I love to travel and learn about other languages and cultures!
2017 Research Abstract
Mutagen Frequencies of DNA Lesion Sequences
containing Oxidized and Chlorinated Products
Sierra Walker, Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND,
Bogdan I. Fedeles, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA,
John M. Essigman, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA,
DNA encodes important information for life, and is, unfortunately, susceptible to damage from biochemical stress. When damaged DNA is unrepaired and replicated, there is the possibility for an error in the coding process. These resulting mutations are then associated risk factors for cancer.
Prolonged inflammation engenders elevated levels of caustic molecules like hypochlorous acid and reactive oxygen species. These may result in oxidation or chlorination of biomolecules. Key examples of functional biomarkers that contribute to cancer are 8-oxoGuanine and 5-ChloroCytosine. A specific repair pathway for this lesion exists, though efficiency depends on sequence context.
This project aims to build understanding of mutagenic frequencies when lesions have the opportunity to interact. The mutagenic properties of both key lesions have been demonstrated in isolated conditions, yet inflamed tissues can accumulate each type simultaneously. Our hypothesis is replication across the 8-oxoG lesion will yield more mutations in the presence of a second lesion (5-chloroC) exactly one position upstream.
Analysis will consist of reviewing the mutation frequency in progeny phage of infected bacteria. Constructs containing lesion sequences and an identifying barcode will be cloned into strains of bacteria that are either proficient or deficient in components of the 8-oxoG repair pathway. Then, samples will be pooled together and mutagenicity will be quantified.
Inflammation is an established risk factor for cancer. Any time a mutation is present, a patient runs the risk of disease. A better understanding of the mechanisms behind DNA repair and under what conditions they fail may lead to better preventative care.