Dr Vincent Cunliffe

vince.jpgSenior Lecturer in Developmental Genetics
Department of Biomedical Science
The University of Sheffield
Western Bank,
Sheffield S10 2TN
United Kingdom

Room: D18d Firth Court
Telephone: +44 (0) 114 222 2389
Email: v.t.cunliffe@sheffield.ac.uk

Bateson Centre


Developmental Biology


Neuroscience


General

Brief career history

  • 2007 - present: Senior Lecturer
  • 2002 - 2007: Lecturer
  • 1997 - 2002: Lister Institute Research Fellow, Department of Biomedical Science, University of Sheffield
  • 1994 - 1997: Group Leader in Molecular and Cell Biology, Therexsys Ltd, Keele, UK
  • 1991 - 1994: Postdoctoral Fellow, Division of Developmental Biology, National Institute for Medical Research, London, UK
  • 1990: Postdoctoral Fellow, Postdoctoral Fellow, Department of Biochemistry, University of Washington, Seattle, USA
  • 1986 - 1990: PhD, Imperial Cancer Research Fund and University College, London
  • 1982 - 1986: BSc, University of Edinburgh

Research interests

Our research is focused primarily on understanding the roles of epigenetic mechanisms in the development and function of the zebrafish Central Nervous System (CNS), and how gene-environment interactions impact on these processes. In addition, we are exploiting the practical advantages of the zebrafish as a model organism to investigate the functions of genes implicated in human neurological disorders and cancer.

Professional activities

  • Organizer, EMBO Practical Courses (1999, 2004, 2007, 2010)
  • Postgraduate Certificate in Learning and Teaching, University of Sheffield (2007)
  • Peer reviewer for scientific journals and grant-awarding bodies
  • Invited speaker at international scientific meetings (European Zebrafish Meeting, International Meeting on Zebrafish Development and Genetics)

Full publications

Research

Integration of synaptic and neuroendocrine signalling and the role of the neural epigenome in health and disease

Epigenetic mechanisms regulate gene expression in response to a wide range of intercellular signals, conferring robustness to developmental processes and ensuring that there is a broad and reliable correspondence between genotype and phenotype. However, it is becoming apparent that epigenetic mechanisms also provide an experience-sensitive interface through which phenotypic plasticity is regulated in response to a wide range of environmental and behavioural signals across the lifecourse, and that these interactions can cause phenotypic changes that may be adaptive or maladaptive.

We aim to understand the roles of the epigenetic machinery, both in conferring developmental robustness and in mediating experience-sensitive phenotypic plasticity, within the zebrafish CNS. A particular focus is on understanding how experience-sensitive changes in synaptic activity and/or neuroendocrine signalling are integrated at the epigenomic level, and how the resulting changes in gene expression affect brain function.

We are collaborating with Dr Nils Krone to elucidate the impacts of altered steroid hormone signaling on zebrafish brain development and function, using novel mutants in which glucocorticoid synthesis and/or signalling is defective. We are also developing zebrafish models of nervous system disorders, such as epilepsy, by generating mutations in zebrafish orthologues of human epilepsy genes that are involved in synaptic vesicle formation and function. These models may be useful subjects of in vivo chemical screens to identify novel therapeutics for epilepsy and other disorders.

Figure 1

Funding:

  • MRC
  • HEFCE

Collaborators:

  • Marysia Placzek
  • Penny Watt
  • Joseph Harrity
  • Val Gillet
  • Richard Baines
  • Enrico Petretto
Teaching

Undergraduate and postgraduate taught modules:

Level 1:

  • BMS109 Pathobiology (Coordinator)
  • BMS109 Molecular Biology

Level 2:

  • BMS238 Cell and Molecular Biology
  • BMS351/BMS6351 Gametes, Embryos and Stem Cells

Level 3:

  • BMS379Cancer Biology
  • BMS370 Developmental Genetics (Coordinator)
  • BMS339 Patients as Educators Project
  • BMS369 Laboratory Research Project

Masters (MSc):

  • BMS6057 Cancer Biology
  • BMS6083 Developmental Genetics (Coordinator)
Opportunities

PhD Studentship Project

Regulation of synaptic protein function by lysine acetylation

Supervisor 2: Dr Mark Collins

Funding status: Competition funded project European/UK students only

This project is eligible for a department scholarship. These scholarships are awarded on a competitive basis – find out more on our funding webpage.

Project Description

Recent proteomic studies have identified several thousand proteins in biochemically purified synapses and have uncovered multi-protein complexes essential for synapse function. Many of these synaptic genes are associated with >100 neurological diseases, highlighting the need for a better a molecular understanding of synapses.

Synaptic activity is regulated by a number of post-translational modifications such as protein phosphorylation. Recent studies have shown that acetylation regulates the localisation of synaptic scaffolding proteins and the surface expression of a major neurotransmitter receptor. The majority of proteins present in mouse/zebrafish synapses are acetylated but almost nothing is known about its function or the mechanism of regulation.

This project will exploit state-of-the-art methods including CRISPR/Cas9 technology in zebrafish, protein biochemistry and quantitative Orbitrap-based mass spectrometry to determine the synaptic targets of enzymes that regulate acetylation levels and to discover how acetylation, in turn, regulates the function of key synaptic proteins. The student will be given in-depth training in these methods and will benefit from collaborations with other groups within the department.

This is a multidisciplinary project between the Collins and Cunliffe labs that will require technology development and cutting-edge methods to generate high-quality quantitative data to understand complex signalling pathways regulating synaptic activity.

References

  • Àlex Bayés, Mark O Collins, Rita Reig-Viader, Gemma Gou, David Goulding, Abril Izquierdo, Jyoti S Choudhary, Richard D Emes & Seth GN Grant. Zebrafish synapse proteome complexity, evolution and ultrastructure. Nature Communications. 2017. Mar 2;8:14613.
  • Wang G, Li S, Gilbert J, Gritton HJ, Wang Z, Li Z, Han X, Selkoe DJ, Man HY. Crucial Roles for SIRT2 and AMPA Receptor Acetylation in Synaptic Plasticity and Memory. Cell Reports. 2017 Aug 8;20(6):1335-1347.

Keywords: Biochemistry, Cell Biology / Development, Genetics, Molecular Biology, Neuroscience/Neurology

For further information about projects within the department and how to apply, see our PhD Opportunities page:

PhD Opportunities

Selected publications

Journal articles