Date of Graduation

5-2023

Document Type

Thesis

Degree Name

Bachelor of Science in Biology

Degree Level

Undergraduate

Department

Biological Sciences

Advisor/Mentor

Harris, Leonard

Committee Member/Reader

Aloia, Lindsey

Committee Member/Second Reader

Iyer, Shilpa

Committee Member/Third Reader

Walker, Kate

Abstract

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized in the S phase of the cell cycle. A series of steps leads from the ICL to the formation of a DNA lesion and double-strand break. The DNA lesion is then repaired by translesion synthesis, and the double-strand break by homologous recombination. The goal of this project is to build a computational model, using the PySB software package, that simulates the biochemical reactions that take place in the FA pathway between proteins and DNA. Once the model was constructed, it produced results that showed DNA damage decreasing over time as it would in the FA pathway, and that protein concentrations changed relative to what events in the pathway were taking place. This model, integrated with other computational models simulating biological events related to the FA pathway, could be used to further the search for druggable targets and improve treatments for individuals with FA.

Keywords

Fanconi anemia; computational modeling; DNA repair; interstrand cross-link; homologous recombination; cancer

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