Major and Classification
Biological Sciences
Faculty Mentor
Peter J. Chung, Ph.D
Department
Physics and Astronomy
Research Gateway Project
The Phosphorylation of the Residues Within the Huntingtin Protein Fragment Htt Exon 1
Project Abstract
Huntington’s disease is a neurodegenerative disease that becomes fatal for patients 15 to 20 years after the first symptom development. Many of Huntington’s disease symptoms have? crucial long-term effects such as mental disorder development and the loss of physical control in motor skills. Huntington’s disease is caused by the ~3000 kDa Huntingtin protein which holds the protein fragment Httexon 1. Within the Httexon 1 fragment, there has been a possible indication of the first protein region called the N terminal and how phosphorylation of residues, adding phosphate groups to the amino acid residue group, inhibits fibril aggregation similar to aggregation found in Huntington’s disease. The Biophysics Chung lab focuses on further purifying and mutating with post-translational mutations the Httexon1 protein fragment critical to this disease with biophysical techniques that can provide similar fibril aggregation to Huntington’s disease. A possible area of interest for an increase in fibril aggregation is the phosphorylation of residue sites within the first 17 amino acid sequences in the N-terminal of the Htt exon 1 fragment. The phosphorylation of the T3, S13, and S16 within this N terminal region has demonstrated through many past scholarships a higher possibility of aggregation within the protein fragment. Under the guidance of Dr. Peter Chung’s lab and its collaboration with the Langen lab, I will analyze the relationship between the phosphorylation of T3, S13, and S16 sites within the N terminal region of the Huntingtin protein. I will then verify its impact on aggregated fibril development in hopes to obtain a similar formation as Huntington’s disease. By invoking phosphorylated sites within the N terminal of the huntingtin protein to aggregate fibril growth, this can be used to further recreate huntingtin fibrils similar to naturally occurring disease fibrils for therapeutic treatments. The development of these fibrils can also be further investigated for the overall understanding of the development of this neurodegenerative disease.