It's a Long Way to the Top If You Wanna Rock 'N' Roll
What we do
Our work combines “small-scale biology” of protein molecular mechanisms and “large-scale” network biology. Specifically, we seek to answer how structural and biochemical properties of GTPases and protein kinases encode complex emergent properties of signalling pathways, enabling them to simultaneously, yet precisely, regulate many cellular processes. Such a systems-view of protein function is essential for achieving truly predictive understanding of how perturbation, such as mutations or therapeutic molecules, affect the phenotype. This level of genotype-to-phenotype mapping would lead to better evaluation of disease mutations and effectiveness of drugs, but it requires an integrated approach of study that combines quantitative measurements of systems level cellular phenotype with fine-grained biophysical models of molecular mechanisms.
We use structural bioinformatics and evolutionary analysis to design targeted perturbations in signalling and regulatory proteins, and biochemically analyse their effects on the molecular function. Our lab develops experimental and computational functional genomics methods that uses these biochemically defined targeted perturbations instead of simple gene knockouts and knockdowns to map functional interactions between and across signalling and regulatory pathways in cells.