Dr Vincent Cunliffe
Senior Lecturer in Developmental Genetics
Room: D18d Firth Court
Brief career history
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.
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.
Undergraduate and postgraduate taught modules:
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.
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.
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:
- Eachus H, Zaucker A, Oakes JA, Griffin A, Weger M, Güran T, Taylor A, Harris A, Greenfield A, Quanson JL, Storbeck K-H, Cunliffe VT, Müller F & Krone N (2017) Genetic disruption of 21-hydroxylase in zebrafish causes interrenal hyperplasia. Endocrinology. View this article in WRRO
- Eachus H, Bright C, Cunliffe VT, Placzek M, Wood JD & Watt PJ (2017) Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function. Human Molecular Genetics, 26(11), 1992-2005. View this article in WRRO
- Vineis P, Chatziioannou A, Cunliffe VT, Flanagan JM, Hanson M, Kirsch-Volders M & Kyrtopoulos S (2017) Epigenetic memory in response to environmental stressors.. FASEB J. View this article in WRRO
- Cunliffe VT (2016) The epigenetic impacts of social stress: how does social adversity become biologically embedded?. Epigenomics, 8(12), 1653-1669. View this article in WRRO
- Cunliffe VT (2016) Histone modifications in zebrafish development. Methods in Cell Biology, 135, 361-385. View this article in WRRO
- Cunliffe VT (2016) Building a zebrafish toolkit for investigating the pathobiology of epilepsy and identifying new treatments for epileptic seizures. Journal of Neuroscience Methods, 260, 91-95.
- Cunliffe VT (2015) Experience-sensitive epigenetic mechanisms, developmental plasticity, and the biological embedding of chronic disease risk. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 7(2), 53-71.
- Jackson HE, Ono Y, Wang X, Elworthy S, Cunliffe VT & Ingham PW (2015) The role of Sox6 in zebrafish muscle fiber type specification. Skeletal Muscle, 5(1), 2-2. View this article in WRRO
- Johnson MR, Behmoaras J, Bottolo L, Krishnan ML, Pernhorst K, Santoscoy PLM, Rossetti T, Speed D, Srivastava PK, Chadeau-Hyam M, Hajji N, Dabrowska A, Rotival M, Razzaghi B, Kovac S, Wanisch K, Grillo FW, Slaviero A, Langley SR, Shkura K, Roncon P, De T, Mattheisen M, Niehusmann P, O’Brien TJ, Petrovski S, von Lehe M, Hoffmann P, Eriksson J, Coffey AJ, Cichon S, Walker M, Simonato M, Danis B, Mazzuferi M, Foerch P, Schoch S, De Paola V, Kaminski RM, Cunliffe VT, Becker AJ & Petretto E (2015) Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus. Nature Communications, 6. View this article in WRRO
- Cunliffe VT, Baines RA, Giachello CNG, Lin W-H, Morgan A, Reuber M, Russell C, Walker MC & Williams RSB (2015) Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms. Seizure, 24, 44-51.