Date of Graduation
Bachelor of Science in Biology
Committee Member/Second Reader
Committee Member/Third Reader
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.
Fanconi anemia, computational modeling, DNA repair, interstrand cross-link, homologous recombination, cancer
Kellett, S. (2023). Development of a Computational Model to Investigate Pathways and the Effects of Treatment in Fanconi Anemia. Biological Sciences Undergraduate Honors Theses Retrieved from https://scholarworks.uark.edu/biscuht/75