Defects in DNA replication during the process of cell division can lead to long-term problems, including loss of genome integrity, irreparable DNA damage, cell cycle exit and senescence. The project will address how genome integrity is ensured during cell division, in particular how chromosomal DNA replication is controlled and coordinated with other cell cycle events. An important regulator of DNA replication is the DBF4-Dependent Kinase (DDK) which controls replication initiation and coordinates it with other cell division events such as sister chromatid cohesion.
Small molecules that can selectively target proteins for degradation, as appose to simply inhibiting their function, are proving to be invaluable research tools for life scientists to understand a wide range of cellular function and provide the potential for a new generation of breakthrough therapeutics. Proteolysis Targeting Chimeras (PROTACs) are two-headed molecules that achieve this goal by simultaneously binding with one head to a target protein and with another head to an E3 ubiquitin ligase, thus inducing the proximity and ubiquitination/degradation of the target protein.
Proteolysis targeting chimeras (PROTACs) are a popular class of bifunctional molecules that simultaneously engage a target protein on one end and an E3 ubiquitin ligase on the other end, forming a ternary complex that facilitates the rapid ubiquitylation and subsequent degradation of the target protein. PROTACs are revolutionizing drug discovery and therapeutic development by destroying rather than merely inhibiting a target protein.
Supervisors : Dr Tony Ly and Professor Julian Blow, Division of Gene Regulation and Expression.