Grant: Maud Menten New Principal Investigator Prize - Biomedical

Ubiquitination is an essential biochemical reaction which occurs in all cells of our body. This process consists of the attachment of a small protein, called ubiquitin, to various cellular proteins. This labeling system marks the target proteins as unwanted (or no longer needed), and induces their degradation by a molecular machine called the "proteasome". Interestingly it has recently been realized that ubiquitination can also cause changes in the function and properties of the targeted protein without any degradation. Moreover we have now started to appreciate that ubiquitination is a dynamic process and that certain enzymes, called deubiquitinases (or DUBs for short), ensure the timely removal of ubiquitin from proteins. In fact, the functional interaction between ubiquitination and deubiquitination allows cells to tightly regulate protein function. With this capability, the ubiquitin system executes and/or regulates many cellular processes, and these include cellular proliferation and differentiation. It is therefore not surprising that alterations in components of the ubiquitin system have been causally linked to several human diseases. The goal of my research is to determine how DUBs orchestrate the function and stability of the genome, a subject about which very little is currently known. I plan to use molecular and cellular biology approaches to characterize the biological function and mechanism of action of a DUB multiprotein complex. This will not only shed new light on the mechanisms that govern normal cellular processes, but will also help in furthering our understanding of various human diseases.