The Leonard lab investigates the mechanisms by which signals are transduced in the cell into appropriate downstream effects. The post-translational modification of proteins with a single phosphate group, a process called phosphorylation, is a ubiquitous signaling mechanism that governs the flow of this information. We are interested in the mechanisms that govern the addition of phosphate groups by KINASES, their removal by PHOSPHATASES, and the structural and functional consequences of these modifications. We use a wide variety of biochemical, biophysical and structural biology tools, complemented with cell biology to explore how cells regulate the transmission of information at the molecular level. More information can be found on the Leonard lab page.
Chk2 is a protein kinase that is best known for its role in checkpoint-mediated cell cycle arrest in response to DNA damage. Chk2 is a multi-organ tumor susceptibility gene and its mutation has been associated with the cancer predisposition disease, Li-Fraumeni Syndrome. The control of Chk2 activity is, therefore, critically important. The goal of the Master’s project will be to elucidate the mechanism by which Chk2 kinase activity is regulated. The project will involve recombinant protein purification, mass spectrometry, quantitative biophysical and biochemical assays and, dependent on progress, possibly some structural biology.
Our motivation to study Chk2 comes from our work on the closely related protein kinase D (PKD), an essential kinase that regulates the process of secretion in cells. We have recently characterized the mechanism by which the kinase activity of PKD1 is regulated and, intriguingly, our findings raise fundamental questions about the regulation of Chk2.
Hold a Bachelor’s degree in biochemistry, chemistry or molecular biology
Have practical experience in molecular biology
who is excited by science
who is fascinated by molecular mechanisms
who is creative, critical, and communicative
Apply now by sending your CV and motivation letter to Thomas Leonard (firstname.lastname@example.org).