Honors Theses
Date of Award
Spring 5-1-2021
Document Type
Undergraduate Thesis
Department
Biomedical Engineering
First Advisor
Nikki Reinemann
Second Advisor
Thomas Werfel
Third Advisor
Dwight Waddell and Patrick Curtis
Relational Format
Dissertation/Thesis
Abstract
Cancer is the second leading cause of death in the United States. Cancerous growth is a result of oncogenes, or mutated genes that increase the rate of cell division in an uncontrolled manner. Cell division, which consists of mitosis and cytokinesis phases, is dependent upon the active movement of kinesin motor proteins along microtubules to rearrange the cytoskeleton for equitable distribution of genetic material to daughter cells. As kinesins are vital to this process, if we could prevent kinesin from binding to the microtubules, cell division would cease.
The goal of this study is to develop a method to prevent cell division by targeting and disrupting kinesin’s microtubule binding sites to prevent them from generating the necessary forces to foster cell growth. The “walking” of the kinesin on microtubules is facilitated by a series of negatively charged residues in the carboxy terminal tail of tubulin known as E-hooks. The processivity of kinesin motor proteins is strongly reduced if E- hooks have been removed from the microtubule surface. It is thought that this is because the E-hooks’ negative charges interact with positively charged domains of the kinesin motor domain. Therefore, we hypothesize that similarly structured, negatively charged peptides could be used to saturate kinesin’s binding sites.
We found that a short E-hook like peptide inhibited kinesin-1 resulting in a decrease in force generated; however, there was minimal effect on velocity. Kinesin-5 is less processive and generates weaker forces than kinesin-1; thus we propose that this effect will be amplified in kinesin-5 and other mitotic kinesin. We hypothesize that inhibiting these motors that play a vital role in mitosis will stop cell division and halt cancerous growth.
Recommended Citation
Murrah, Ashton Ward and Howard, Baylee Hope, "Analyzing the Effects of E-hook Peptides on Kinesin-1" (2021). Honors Theses. 1646.
https://egrove.olemiss.edu/hon_thesis/1646
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