Exploring the Post-Translational Landscape of Tuberin and its Function as a Cell Cycle Regulator

Standing

Graduate (Masters)

Type of Proposal

Oral Presentation

Faculty

Faculty of Science

Proposal

The cell cycle is a tightly regulated process by which a single cell undergoes distinct phases of cell growth and DNA synthesis to produce two daughter cells. The processes and proteins involved in the regulation of the phases are well characterized, however, the processes that permit each cell to transition between the phases are less well known. Our lab is currently studying the protein, Tuberin, as a potential regulator of these transition points. Previous data from our lab shows that Tuberin is able to bind the important G2 cyclin, Cyclin B1, to delay transition into mitosis. Tuberin is highly regulated by several nutrient sensing and stress sensing pathways and is therefore one of few proteins associated with the cell cycle that can determine the state of the intracellular environment. This unique ability leads us to believe that Tuberin plays a role in the onset of mitosis and transition through the G2/M checkpoint. However, Tuberin has very little structural data available, so combat this concern, we have developed collaborations with computational biochemists to help determine the specific residues that allow Tuberin and Cyclin B1 to interact. Using a mutagenesis model, we will be testing the in silico derived mutations in vitro to determine the essentiality of the predicted residues. This project will allow us to discern many unknowns about this crucial protein. Moreover, Tuberin and Cyclin B1 have also been implicated in a number of cancers and this data could provide crucial information for developing therapeutics targeting these G2 phase proteins.

Location

University of Windsor

Grand Challenges

Viable, Healthy and Safe Communities

Special Considerations

I understand the is a late submission, but I had emailed the committee earlier not realizing I needed to apply through this website. You can see my earlier e-mail if you have concerns.

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Exploring the Post-Translational Landscape of Tuberin and its Function as a Cell Cycle Regulator

University of Windsor

The cell cycle is a tightly regulated process by which a single cell undergoes distinct phases of cell growth and DNA synthesis to produce two daughter cells. The processes and proteins involved in the regulation of the phases are well characterized, however, the processes that permit each cell to transition between the phases are less well known. Our lab is currently studying the protein, Tuberin, as a potential regulator of these transition points. Previous data from our lab shows that Tuberin is able to bind the important G2 cyclin, Cyclin B1, to delay transition into mitosis. Tuberin is highly regulated by several nutrient sensing and stress sensing pathways and is therefore one of few proteins associated with the cell cycle that can determine the state of the intracellular environment. This unique ability leads us to believe that Tuberin plays a role in the onset of mitosis and transition through the G2/M checkpoint. However, Tuberin has very little structural data available, so combat this concern, we have developed collaborations with computational biochemists to help determine the specific residues that allow Tuberin and Cyclin B1 to interact. Using a mutagenesis model, we will be testing the in silico derived mutations in vitro to determine the essentiality of the predicted residues. This project will allow us to discern many unknowns about this crucial protein. Moreover, Tuberin and Cyclin B1 have also been implicated in a number of cancers and this data could provide crucial information for developing therapeutics targeting these G2 phase proteins.