Cell Signalling and Adhesion

Our group studies regulatory mechanisms of key signalling switches controlling growth and adhesion signals, which regulate important cellular processes such as cell proliferation, migration and survival. In cancer these signals are responsible for triggering tumour invasion and metastasis. We use structural techniques, such as X-ray crystallography and electron microscopy, in combination with biochemical and functional studies to understand at atomic level how specific growth and adhesion signals are regulated and to rationalise how oncogenic events result in their deregulation. The structural understanding allows us to design potential anti-cancer therapeutics that interfere with oncogenic deregulation. To this end we perform a fragment based drug discovery approach to develop highly selective allosteric inhibitors for potential cancer therapy. Our projects focus on growth and adhesion signalling systems that interact and are regulated by specific lipids in the plasma membrane. Specifically, we pursue the following questions: (i) How are signals in focal adhesion complexes triggered upon assembly of the complex on the plasma membrane? (ii) Using insights from (i), can we develop allosteric inhibitors that highly selectively block focal adhesion signals and could prevent tumour invasion and metastasis  (ii) How are the levels of specific membrane lipids regulated to control growth and adhesion signals?