Professor Gwyn Gould
- Professor of Cell Biology (Institute of Molecular Cell and Systems Biology)
telephone: 01413305263
email: Gwyn.Gould@glasgow.ac.uk
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https://orcid.org/0000-0001-6571-2875Biography
Gwyn was born and raised in South Wales and read Biochemistry at the University of Southampton, graduating in 1983. He undertook his PhD in membrane biophysics with Tony Lee, studying aspects of the kinetics of the Ca2+ ATPase of sarcoplasmic reticulum, and the impact of phospholipid geometry on the function of this pump. In 1986, he moved to Dartmouth Medical School to work with Gus Lienhard on glucose transport, supported by a fellowship from the Juvenile Diabetes Foundation International. This began a 30-year career studying aspects of glucose transport. After visiting scientist posts at Washington University School of Medicine St. Louis and University of California Los Angeles, he moved to Glasgow in 1989. During his time at Glasgow, Gwyn has held a Lister Institute of Preventive Medicine Research Fellowship and a Wellcome Trust Research Leave post. He has been Professor of Cell Biology since 2005. Research in his lab is presently supported by Diabetes UK, The British Heart Foundation and the Novo Nordisk Research Foundation.
Research interests
Insulin stimulates glucose transport into fat and muscle by regulating delivery of the facilitative glucose transporter GLUT4 from an intracellular store to the cell surface. Upon binding its receptor, insulin initiates a signalling cascade that culminates in changes in the trafficking itinerary of GLUT4, releasing it from its intracellular store and delivering it to the cell surface. Individuals with insulin resistance and Type-2 diabetes exhibit defective insulin-stimulated GLUT4 translocation and consequently much effort has gone into defining the trafficking of GLUT4 in adipocytes, cardiomyocytes and muscle cells. Our work in this area seek to define the mechanisms which control GLUT4 sorting/trafficking, the mechanism by which GLUT4 is delivered to the cell surface, and the processes which control its spatial distribution on the cell surface.
Present projects include:
• Understanding the interface of insulin signalling and membrane trafficking: defining how tyrosine phosphorylation of key trafficking machinery impacts GLUT4 delivery to the cell surface and the spatial relationship of insulin signalling and trafficking hubs.
• Examination of the relationship between insulin sensitivity and SNARE protein phosphorylation in human populations.
• Using unorthodox kinases to regulate GLUT4 trafficking in insulin-sensitive tissues as an alternative therapeutic target.
• Defining the mechanisms by which insulin regulates the cell surface distribution of GLUT4 using cell biological, genetic and super-resolution approaches.
• Developing the use of induced pluripotent stem cell-derived cardiomyocytes as model systems for the study of diabetic cardiomyopathy
• Using ontogenetic approaches to modulate glucose transport in cardiomyocytes and myotubes.
• Defining the role of cholesterol in insulin sensitive cells and tissues.
Research interests - further information
Grants
Grants and Awards listed are those received whilst working with the University of Glasgow.
- BBSRC iGEM sponsorship 18/19-20/21
Biotechnology and Biological Sciences Research Council
2018 - 2021
- Wellcome 2018 iGEM
Wellcome Trust
2018 - 2019
- Syntaxin Phosphorylation as an insulin-regulatory node of Glut4 sorting in human muscle of individuals with type 2 diabetes
The Novo Nordisk UK Research Foundation
2017 - 2020
- How does Cholesterol regulate insulin action in adipocytes?
Diabetes UK
2016 - 2019
- Control of GLUT4 sorting by Syntaxin 16 and mVps45 in adipocytes
Diabetes UK
2014 - 2016
- Commonwealth Fellowship
Commonwealth Scholarship Commission in the UK
2012 - 2012
- How does tyrosine phosphorylation of SNARE proteins control GLUT4 vesicle fusion with the plasma membrane?
Diabetes UK
2012 - 2015
- Role of ubiquitination as a transient modification in regulated protein trafficking
Medical Research Council
2012 - 2015
- The sensitive assessment of the activity of cellular signalling pathways regulating insulin action and the cardiovascular complications of diabetes
Diabetes UK
2011 - 2014
- Investigation of the role of Syntaxin 16 and mVps45 in cytokinesis
Cancer Research UK
2011 - 2015
- How does Syntaxin 16 control Glut4 sorting?
Diabetes Research & Wellness Foundation
2011 - 2012
- Regulation and role of the Exocyst complex in cytokinesis.
Cancer Research UK
2010 - 2011
- How does mVps45 regulate Glut4 sorting in adipocytes
Diabetes UK
2010 - 2012
- Phosphoryaltion of FIP3 and its consequence for cytokinesis
Cancer Research UK
2009 - 2012
- Tyrosine phosphorylation of Munc18c in insulin action
Diabetes Research & Wellness Foundation
2009 - 2009
- Translational analysis of the role of synaptotagmins in the adipocyte, and their relationship to insulin action
Scottish Executive Health Department
2008 - 2010
- The role of mvps45 in Glut4 trafficking in adipocytes
Diabetes UK
2007 - 2007
- Functional analysis of Munc18c/Syntaxin4 interactions
Biotechnology and Biological Sciences Research Council
2005 - 2008
- The role of Rab 11-FIP3 and Rab 11-FIP4 in cytokinesis
Biotechnology and Biological Sciences Research Council
2005 - 2009
- The role of arfophilins in cytokinesis
Wellcome Trust
2004 - 2007
- Functional analysis of the adipocyte secreted proteome
Biotechnology and Biological Sciences Research Council
2004 - 2007
- Compartmentalisation of insulin signalling in human adipocytes - role of raft associated structures
Scottish Executive Health Department
2003 - 2007
- The role of synaptotagmins in GLUT4 translocation in the adipocyte
Diabetes Research & Wellness Foundation
2003 - 2006
- The role of synaptotoagmins in GLUT4 translocation in the adipocyte Dr S Miller
Medical Research Council
2003 - 2006
- Subcellular compartmentalisation analysis by confocal microscopy
Biotechnology and Biological Sciences Research Council
2003 - 2007
- Lipid rafts and the spatial control of exocytosis
Biotechnology and Biological Sciences Research Council
2002 - 2005
- Role of Arf5 and Arf6 in regulated membrane trafficking in adipose cells
Biotechnology and Biological Sciences Research Council
2000 - 2005
Teaching
- Masters: Lectures on 'Endocrinology' and 'Diabetes' M.Sc. courses.
- Masters: Discussion facilitator on 'Endocrinology' and 'Diabetes' M.Sc. courses.
- Level 4: Option Central Approaches in Biochemistry lectures on Membrane biogenesis, function and transport
- Level 4: Option Central Approaches in Biochemistry - tutorial leader
- Level 4: Option Cell Compartmentalisation and Function Coordinator
- Level 4: Option Cell Compartmentalisation and Function lectures on membrane trafficking, SNARE protein biology and membrane scission.
- Level 3: Biochemistry Overall Course Coordinator.
- Level 3: Block Leader; Membranes and Filaments.
- Level 3: Lab classes for Biochemistry and Molecular Cell Biology students.
- Level 3: Lectures on Bioenergetics (Biochemistry students) and Membrane Biology (Biochemistry, Genetics and Molecular Cell biology students)
- Level 3: Data handling sessions; Careers Sessions; Employability workshops.
- Level 3: "How to read a paper"
- Level 3: Tutorial leader.
- Level 2: Overall Coordinator 'Genes. Molecules and Cells-2', compulsory second year course for all bimolecular science students.
- Level 2: Lectures on 'Genes, Molecules and Cells-2' (Protein Structure and Function; Signalling and Cell Compartmentalisation).
- Level 2: Laboratory classes in 'Genes. Molecules and Cells-2'
- Level 2: Lectures on 'Fundamental Topics in Biology-2' compulsory course.
- Level 2: Block leader on 'Fundamental Topics in Biology-2' course.
- Level 2: Laboratory classes on 'Fundamental Topics in Biology-2' course.
- Level 2: Fundamental Topics in Biology 2; Block Leader "Systems to Cells"
- Academic Advisor of Studies.
- Member College Teaching and Learning Committee.
- Member and Chair, Institute Teaching and Learning Committee.
Additional information
Editorial Board
- 2017 - present: Scientific Reports - Editorial Board Member
- 2017 - present: PeerJ - Editorial Board Member
- 2005 - 2010: Biochemical Journal
- 2004 - 2010: Endocrinology
- 1995 - 1998: Biochemica et Biophysica Acta
- 1992 - 1997: Biochemical Journal
Grant Advisory Board
- 2009 - present: Qatar Medical Research Foundation
- 2004: Scottish Executive - Director of Chief Scientists Office Sub-Committee to Review Translational Diabetes Research in Scotland
- 2002 - 2003: Scottish Executive - Chief Scientists Office Committee to Review Needs of Diabetes Research in Scotland
- 2002: BBSRC - Chair, Sequencing Needs Review Panel
- 2001 - 2004: BBSRC - Strategy Board
- 1999: Diabetes UK - Studentship & Fellowship Committee
- 1999 - 2004: BBSRC - Biochemistry & Cell Biology Committee Member, Chairman 2001-04
Invited International Presentations
- 2015: Glasgow, UK - Glasgow Diabetes UK Professional Conference: 'SNARE proteins in the control of glucose transport'.
- 2014: London, UK - London Diabetes UK Professional Conference - basic science presentation judge.
- 2010: Oxford, UK - Co-organiser, "Cell Organization through the Cell Cycle." British Society of Cell Biology satellite meeting.
- 2009: Glasgow, UK - Invited Speaker, CR-UK Beaton Meetin "Vesicle Trafficking in Cancer"
- 2009: Colorado, USA - Invited speaker, FASEB 8th Glucose Transporter Biology.
- 2009: Vienna, Austria - Invited Speaker, European Association for the Study of Diabetes Conference
- 2009: Oxford, UK - Invited speaker "Cell Organization through the Cell Cycle." British Society of Cell Biology satellite meeting.
- 2008: Edinburgh, UK - Co-organiser, "Mechanics and Control of Cytokinesis meeting"
- 2007: Il Ciocco, Italy - FASEB Summer Research Conference on Arf GTPases
- 2007: Colorado, USA - FASEB Summer Research Conference on Glucose Transporter Biology
- 2005: Biosciences 2005 - Keynote Speaker
- 2004: Vermont, USA. - American Society for Cell Biology Satellite Symposium, Cytokinesis
- 2003: Glasgow Cell Biology Inaugural Meeting
- 2003: Glasgow, UK. - Society for Experimental Biology
- 2002: San Francisco, USA. - American Society for Cell Biology
- 2002: Heidelberg, Germany. - EMBL Predoctoral Student Symposium
- 2001: Colorado, USA. - FASEB Meeting, Glucose transporter biology.
- 2001: American Diabetes Association
- 2001: Diabetes UK
Professional Learned Society
- 2005 - present: Biochemical Society - Member
- 2005 - present: American Endocrine Society - Member
- 2004 - present: American Society of Biochemistry and Molecular Biology - Member
- 2002 - present: British Cell Biology Society - Regular Member
- 1999 - present: American Society of Cell Biology - Regular Member
- 1998 - present: Lister Institute of Preventive Medicine
- 1992 - present: American Diabetes Association
Research Fellowship
- 2004 - 2007: Wellcome Trust Research Leave Fellowship
- 1992 - 1998: Lister Institute Fellowship
Supervision
The interface of insulin signalling and membrane trafficking.
Insulin binding activates the intrinsic tyrosine kinase activity of the receptor beta-subunit. Although the essential role of two major targets for this kinase, IRS1 and IRS2, in metabolic regulation is clear, little is known about the role of insulin-stimulated tyrosine phosphorylation of other proteins. Syntaxin 4 and Munc18c, proteins intimately involved in the insulin-stimulated translocation of the facilitative glucose transporter, GLUT4, to the plasma membrane are both tyrosine-phosphorylated within minutes of insulin stimulation. Our recent work has established that these phosphorylation events have key functional consequences. We now wish to determine how the signalling and trafficking machinery is co-located within cells, and to determine whether alterations in this underly insulin resistance.
How does phosphorylation of Sx16 regulate GLUT4 sorting?
A key action of insulin on adipose and muscle cells is to initiate a signalling cascade that changes the trafficking facilitative glucose transporter GLUT4, releasing it from a specialised intracellular store and delivering it to the cell surface. Individuals with insulin-resistance and Type 2 Diabetes exhibit significantly impaired insulin-stimulated glucose transport, and this appears to be largely due to a failure of GLUT4 translocation. Understanding how GLUT4 trafficking is controlled at the molecular level is therefore an essential step in the development of effective therapies against the current global epidemic of insulin-resistance and diabetes.
This project seeks to understand the sorting of GLUT4 into its specialised storage compartment. We will build our published and unpublished data to further our understanding of the role that the SNARE protein Syntaxin-16 plays in this process, and in particular how regulated phosphorylation of Syntaxin-16 controls GLUT4 sorting.
Control of GLUT4 dispersal by regulation of the plasma membrane lipidome.
It has recently been discovered that in addition to regulating delivery of GLUT4 from intracellular stores to the plasma membrane, insulin also regulates the spatial organisation of GLUT4 at the cell surface. This project builds upon findings from our lab to understand the molecular mechanisms that control this recently described effect of insulin. The project will investigate how patches at the cell surface of adipocytes that are enriched in phosphatidylinositol-4-phosphate contribute to GLUT4’s localisation and functionality and also how these patches are regulated by insulin. The potential that this aspect of insulin action in impaired in Type-2 diabetes will also be examined.
A Model for Diabetic Cardiomyopathy.
Metabolic disorders such as obesity, insulin resistance and type 2 diabetes (T2DM) mellitus are all linked to the development of cardiovascular disease. The World Health Organisation has projected that T2DM will be the seventh leading cause of death by 2030. Cardiovascular disease represents the single biggest cause of death in these patients, and all present studies suggest that diabetes has a negative effect on cardiac muscle independently of concurrent vascular disease. This project will use cardiomyocytes derived from induced pluripotent stem cells and model the effects of a prediabetic milieu on differentiation, gene expression and insulin sensitivity in this system in order to better understand changes associated with diabetic cardiomyopathy.
Excitation contraction coupling and glucose transport.
A key action of insulin is to increase glucose uptake into cardiomyocytes via GLUT4 translocation to the cell surface. In cardiac tissue, exercise and electrophysiological activity can also promote GLUT4 translocation. However the mechanism(s) that couple electrical activity to the control of GLUT4 availability at the cell surface remain unidentified. This project will test the hypothesis that a direct link between channels on the cell surface and the GLUT4 vesicle fusion machinery controls GLUT4 vesicle exocytosis, and that this is impaired in diabetic cardiomyopathy. We will also develop ontogenetic approaches to regulate GLUT4 activity in muscle and cardiomyocytes.
