Sarah Overall

Background

About Sarah Overall

Redefining structural biology: towards in situ structure determination with DNP solid-state NMR I've had a long fascination with the immune system, how the immune system distinguishes self from non-self, how viruses and cancer evade these mechanisms and defining the molecular and atomic details of self/non-self recognition by the immune system. The engagement of membrane proteins that trigger distinct signalling cascades is a key area in which the immune system can be influenced or controlled through cell based therapeutics and biologics towards eradication of HIV and the treatment of cancer. But the cellular context is critical! We need new methods that can reveal structural and molecular interactions of membrane proteins with signalling molecules as well as with the complex cellular membrane within cells. I am dedicated towards developing these tools, particularly through in-cell DNP-NMR which is one of few, if not the only technique, that has the potential for structure determination with atomic resolution of membrane proteins and transient signalling complexes within the context of intact cells. I am interested in- genetically encoded stable isotope labeling through biochemical engineering and chemical biology techniques- solid-state NMR methods for spectral editing of complex cellular samples under DNP conditions- development of NQR methods for applications to time resolved membrane protein structure and membrane binding- Quadrupolar nuclei and CSA parameters as measures of hydrogen bonding in membranes and membrane microdomains (lipid rafts)- development of new isotopically labelled membrane probes for in situ characterisation of membrane structure within cells- Application of the information gained to a deeper understanding of TCR:CD3 signal transduction, THEMIS regulation of TCR signalling, determination of critical factors in PKC membrane association in cell membranes-Applications to new chimeric antigen receptors (CARs) for anti-cancer therapies and CAR efficacy diagnostics.