School of Medical Sciences Special Seminar
Dr Ben Goult - School of Biosciences, University of Kent
Bio: Dr Ben Goult obtained his degree in Biochemistry at the University of Sheffield, before his PhD in the labs of Dr Tim Norwood (University of Leicester) and Professor Lu-Yun Lian (University of Leicester/ Manchester) developing NMR based approaches for detecting small molecule binding to target proteins, a first step in drug discovery. Following a 2-year postdoc at the University of Manchester he moved to AstraZeneca Alderley Park as a Senior Scientist. In 2005, Ben returned to Leicester to work with Professor David Critchley on the proteins that regulate cell adhesion and migration, in particular the FERM domain containing proteins talin and kindlin; key players in integrin mediated adhesion. In 2014, Ben moved to the University of Kent to start his own research group.
Abstract: Cell adhesion to the extracellular matrix (ECM), mediated by integrins, is highly sensitive to biochemical, structural, and mechanical features of the ECM. Talin, a key link between integrins and actin, coordinates force-dependent binding of numerous cytoskeletal and signaling adaptors. Talin thus comprises a series of mechanochemical switches decorated with various ligand proteins, forming a “Mechanosensitive Signaling Hub” (MSH). We propose that the talin MSH integrates the magnitude and history of mechanical forces, the expression and activation state of ligand proteins, and its own post-translational modifications to determine adhesion structure and signaling outputs.
The ability of talin to parse diverse inputs to determine robust, reproducible signaling responses leads us to view the talin MSH as a type of “code”; that is, a network of binding events organized in time and space that confers meaning in the form of signaling outputs. Such a “talin code” may explain how cells interpret complex chemical and physical information to coordinate their behaviors.
I will discuss our efforts to define in molecular and biophysical terms how forces transmitted via integrins regulate cell phenotype. Integrating biochemistry, structural biology and bioengineering in vitro and in vivo, we have begun to decipher the talin mechanotransduction code at the atomic level.
More info: Dr John Lock at email@example.com