Professor Nia Bryant

Chair of Cell Biology

Overview

Control of Intracellular Membrane Traffic

A defining feature of eukaryotic cells is their compartmentalization into discrete membrane-bound cytosolic organelles. While each organelle maintains its own unique complement of macromolecules necessary for its particular function, there is a high level of communication (exchange of material) between these various intracellular compartments. This is facilitated through membrane fusion events, in many cases by vesicular transport where cargo molecules, both membrane-bound and soluble, are packaged into vesicles that bud from the donor compartment.  These vesicles then dock and subsequently fuse with the appropriate target organelle, delivering their contents. 


Legend Needed ............. 

Figure 1

Non-disruptive transportation of molecules between these organelles and to the plasma membrane is extremely important, and each trafficking event is tightly regulated both spatially and temporally – i.e. it is imperative that each transport vesicle docks and fuses with the right target compartment at the right time. SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins are central to this process, facilitating fusion by formation of specific complexes between SNAREs on opposing lipid bilayers, through their highly conserved α-helical cytosolic SNARE motifs.

Regulating SNARE complex assembly provides the cell with a means to regulate membrane traffic. Understanding this process is important, as it underpins many physiological and developmental processes and is dysregulated in numerous disease states, including cancers, diabetes and neurodegenerative disorders.

As with many processes in eukaryotic cell biology, the molecular mechanisms that regulate membrane traffic are conserved through evolution from yeast to humans. We therefore use the genetically tractable model eukaryote Saccharomyces cerevisiae (Baker’s yeast) to study human diseases such as neutropenia (which we have mapped to a defect in the SNARE regulator Vps45).


This figure shows 3T3-L1 adipocytes expressing a version of GLUT4 harbouring an HA-epitope tag in its first exofacial loop treated with 100nM insulin
(right-hand panel) or not (left-hand panel) for 30 minutes prior to labelling for surface (blue) and total (green) GLUT4.

Figure 2

We are particularly interested in how the hormone insulin regulates membrane traffic in fat and muscle cells. This is an important goal, as defects in this system underlie Type-2 Diabetes, a debilitating disease whose incidence is increasing worldwide at an exponential rate. One of the major actions of insulin is to bring about changes in the membrane trafficking of a glucose transporter called GLUT4 that deliver it to the cell surface. We have discovered that this is achieved by altering the way in which SNARE complexes are formed. As this system is dysfunctional in individuals suffering from Type-2 Diabetes, this discovery has diagnostic and therapeutic potential.

Another exciting project in our lab involves using our knowledge of membrane traffic to enhance the secretory capacity of cells that are used to produce monoclonal antibodies for therapeutic purposes. This has the potential to greatly reduce the cost of these medicines and thus contribute to healthcare worldwide.

Research Group

NameStatusProject
Dimitrios Kioumourtzoglou Senior Research Technician A combinatorial approach to enhance production of monoclonal antibodies.
Agnieszka Urbanek  Postdoctoral Research Associate A combinatorial approach to enhance production of monoclonal antibodies.
David Mentlak  Postdoctoral Research Associate A combinatorial approach to enhance production of monoclonal antibodies.
Hannah Black PhD Student Impact of tyrosine phosphorylation of Syntaxin4 and Munc18c on GLUT4 translocation.

Teaching and Scholarship

teaching icon
I am a neuroscientist and teach primarily in this area. I take students through the scientific approaches and landmark studies that have helped unravel fundamental mechanisms and concepts with a view to helping students develop problem-solving skills applicable to any biological field.

lectures icon‌‌

I lecture in the Stage 2 Neuroscience module and run the Stage 3 Learning and Memory module.  My lecture material aims to help students understand how synaptic transmission is modulated at the cellular level and how this underpins behaviours such as addiction, circadian rhythms and cognition. Evaluating the evidence from scientific studies for established knowledge and concepts is an important feature of my lectures.

tutorials icon

My tutorial sessions for Stage 1 students aims to introduce them to ground-breaking work that has dramatically advanced biological understanding. This is done through critical discussions on Nobel prize-winning discoveries where students are free to choose a particular Nobel Prize or Nobel Laureate. For Stage 2 students I run tutorials on Cell Signalling where we consider how fundamental calcium signalling mechanisms are deployed in different cell types to mediate distinct physiological functions.

projects icon


Undergraduate projects in the lab are aligned to our research interests in the timekeeping mechanisms of cellular circadian clocks. We investigate this in model organisms such as the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans

 

Publications


PURE Staff link York Research Database

Visit Professor Nia Bryant's profile on the York Research Database to:
See a full list of publications
Browse activities and projects
Explore connections, collaborators, related work and more

Professor Nia Bryant
Chair of Cell Biology

Profile

Career

 

2014 Chair of Cell Biology Department of Biology, University of York
2013 Professor of Molecular Cell Biology Institute of Molecular,
Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow
2010 - 2013  Reader Institute of Molecular,
Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow
2006 - 2010 Senior Lecturer, and Prize Fellow
Lister Institute of Preventive Medicine
(from 2004)
Division of Molecular and Cellular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow
2003 - 2006 Lecturer Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow
2002 - 2003 Research Fellow       Garvan Institute of Medical Research, Sydney, Australia  
1998 - 2002 Senior Research Officer       Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.  
1994 - 1998

Post Doctoral Fellow

Institute of Molecular Biology, University of Oregon, Eugene, OR.  U.S.A.
1992 - 1994 Temporary Lecturer Department of Biochemistry, University of Edinburgh
1993

Ph.D. in Biochemistry

University of Edinburgh
1989 B.Sc. (Hons Biochemistry) Biological Sciences, University of Edinburgh

Research

Overview

KEY RESEARCH INTERESTS AND DISCOVERIES

Two interrelated areas:

Regulation of SNARE-mediated membrane traffic
Understanding the regulation of membrane traffic is an important goal in cell biology as this process underlies many physiological processes.  We use a variety of systems, from yeast to mammalian cells, to study this.

Insulin-regulated trafficking of GLUT4
Insulin increasing the rate of glucose transport into fat and muscle by delivering the facilitative glucose transporter GLUT4 from intracellular stores to the cell surface.  This regulated membrane trafficking process is defective in the disease state of Type-2 diabetes.  We aim to define the molecular mechanisms that regulate GLUT4-trafficking in fat and muscle cells.

Shewan, A.M., McCann, R.K., Lamb, C.A., Stirrat, L., Kioumourtzoglou, D., Adamson, I.S., Verma, S., James, D.E. and Bryant, N.J. (2013) Endosomal sorting of GLUT4 and Gap1 is conserved between yeast and insulin-sensitive cells. J Cell Sci. 126, 1576-1582.

Coonrod, E.M., Graham, L.A., Carpp, L.N., Carr, T.M., Stirrat, L. Bowers, K, Bryant, N.J. and Stevens, T.H. (2013) Homotypic Vacuole Fusion in Yeast Requires Organelle Acidification and not the V- ATPase Membrane domain.  Dev. Cell. 27, 462-468.

Discoveries (last 18 months)

The molecular mechanisms that regulate membrane traffic are conserved through evolution, from yeast to humans.  My lab performed studies in yeast to demonstrate that mutations, in a gene called VPS45, identified in (human) patients suffering from a congenital form of neutropenia and primary myelofibrosis are directly responsible for defects in cell organisation.  This discovery is important as it can aid early diagnosis.

Professional activities

  • Journal editorial (and advisory) boards: The Biochemical Journal, Traffic, Frontiers in Endocrinology (specializing in Medical Molecular Biology and Biochemistry)
  • Fellow of the Society of Biology
  • Ambassador for The British Society of Cell Biology
  • Member of the Biochemical Society

Projects

Control of GLUT4 sorting by Syntaxin16 and mVps45, Funding body: Diabetes-UK

Ubiquitination as a transient modification in regulated protein trafficking, Funding body: MRC

How does tyrosine phosphorylation of SNARE proteins control GLUT4 vesicle fusion with the plasma membrane? Funding body: Diabetes-UK

Research group(s)

StatusNameProject
Senior Research Technician Dimitrios Kioumourtzoglou A combinatorial approach to enhance production of monoclonal antibodies
Postdoctoral Research Associate Agnieszka Urbanek A combinatorial approach to enhance production of monoclonal antibodies
Postdoctoral Research Associate David Mentlak A combinatorial approach to enhance production of monoclonal antibodies
PhD student Hannah Black Impact of tyrosine phosphorylation of Syntaxin4 and Munc18c on GLUT4 translocation

Professor Nia Bryant

Contact details

Prof. Nia Bryant
Department of Biology (B/J008)
University of York
Heslington
York
YO10 5DD

Tel: +44 (0)1904 328622