Chemical Genetics Approach: Function and Inhibitory Effect on Kinesins

This program is to analyze the regulation of cell cycle progression and the mechanism of chromosome segregation with regard to Kinesin5 and Kinesin8 families. Defects in these processes can result in the formation of aneuploid cells, a hallmark of many solid cancers. Thus, insights into the function and regulation of Eg5 and Kif18A (one protein of Kinesin8 families)will not only contribute to a better understanding of the mitotic and meiotic cell division but also how malfunctions in these pathways promote tumor formation in men. We will apply Chemical Biology approach (i.e. use small molecules to modulate functions proteins in living cells) to alter the functionality of kinesins in cells in a fast and often reversible manner. The model systems are human cancer cell lines and Xenopus laevis oocytes and embryos. We hope to find cellular binding partners of the immobilized compounds which rescue the monastrol-treated (an anti-tumor drug) Hela cells, and optimizing the chemical properties of BTB-1, a small molecule that inhibits the ATPase activity of Kif18A (which inhibit mitosis, then the cell cycle will cease).

Faculty Supervisor:

Yuliya Lytvyn

Student:

Partner:

University of Konstanz

Discipline:

Life Sciences

Sector:

Education

University:

University of Toronto

Program: