Dr Ben Goult
Senior Lecturer in Biochemistry
School of Biosciences, Ingram 421A
- 01227 816142
- 1995-1998 University of Sheffield: BSc(Hons) Biochemistry 2:1
- 1998-2002 UMIST: PhD in Biological Science
- 2003-2005 University of Manchester: Research Associate
- 2005-2006 AstraZeneca Alderley Park: Senior Physical Scientist
- 2006-2012 University of Leicester: Research Associate
- 2012-2014 University of Leicester: Research Fellow
Dr Ben Goult obtained his first degree in Biochemistry at the University of Sheffield in 1998, before embarking on a 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 2year postdoctoral position at the University of Manchester he moved to AstraZeneca Alderley Park as a Senior Physical 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 2010, he was awarded a Wellcome Trust Project Grant to work on another FERM domain protein, IDOL, an E3-ligase that regulates levels of the LDL-Receptor via ubiquitination. IDOL is a potential drug target for the treatment of hypercholesterolemia.
Ben joined the School of Biosciences in August 2014 where his research group specializes in the structural and biochemical studies of cell-extracellular matrix (ECM) adhesion complexes.
Ben is a member of the Protein Form and Function Group.back to top
- Cell-extracellular matrix (ECM) adhesion complexes, FERM domains
- Structural Biology: NMR Spectroscopy, X-Ray Crystallography and Small Angle X-Ray Scattering (SAXS)
My research involves the use of biophysical techniques to understand the structure and function of proteins that are involved in the process of Cell-extracellular matrix (ECM) adhesion. Such adhesion proteins are increasingly recognised as potential targets for therapeutic intervention in a range of pathologies including immune and vascular disorders, blood clotting, skin blistering, wound healing and cancer.
Talin, a master mechanosensor regulating cell-matrix adhesion assembly
Our recent structural characterisation of talin (Goult et al. JBC 2013) has provided new insights into how talin performs its multiple different roles and we are now using a combination of biochemical and biophysical techniques to investigate physiologically relevant, force dependent, conformational changes in talin that regulate its function.
Fig.1 Model of talin showing the structures of all 18 domains
The talin rod is comprised of 4- and 5-helix bundles, each with distinct mechanical and ligand binding profiles. Each domain has a unique binding profile and can be generally defined as; (i) mechanically sensitive, (ii) mechanically insensitive, (iii) mechanically sensitive but protected from mechanical force, (iv) mechanically sensitive only under certain conditions. The arrangement of these domains has profound implications for how talin functions as a molecular biosensor.
Talin has a large number of binding partners including RIAM, vinculin, actin, integrin, synemin, DLC1 and also talin, each binding to different regions of the rod. As such, this knowledge of the domain structure of talin is enabling us to study these interactions and gain a better understanding of the complex roles talin plays in regulating cellular adhesion to the extracellular matrix.
Fig.2 Talin changes binding partners in response to force induced conformational change
Stretching single Talin molecules.
Rapid progress in single-molecule force manipulation technologies have made it possible to directly study the impact of mechanical force on talin conformations and its interactions with other signaling proteins.By using magnetic tweezers we are able to stretch single talin molecules and explore their structural and biochemical properties as a function of force.
Fig. 3 A single talin molecule is attached between a surface and a paramagnetic bead. Forces are applied to the bead by a pair of permanent magnets. The force dependence of the interactions between talin and its ligands can then be studied in the absence and presence of force
Such techniques are enabling us to study the mechanical properties of each individual talin domain and characterise force dependent protein interactions
Fig.4 Stretching a single talin molecule. (a) the compact N-terminal fragment of the talin rod contains three domains, R1, R2 and R3. (b) The three helical bundles unfold in three distinct steps consistent with the domains unfolding independently. (c) A stabilising mutant in R3 (IVVI) shifts the initial unfolding event confirming R3 as the initial unfolding mechanosensor.
We are using this approach to fully characterise how talin functions as a mechanosensor.
If you are interested in joining the group then please contact:
Dr Ben Goult
- BI301 Enzymes and Introduction to Metabolism
- BI602 Cellular Communication 1