Dr William Davies

Senior Lecturer

Research group:
Neuroscience
Email:
DaviesW4@cardiff.ac.uk
Telephone:
+44(0)29 2087 0152 (PSYCH)
+44(0)29 2068 8462 (MEDIC)
Location:
Tower Building, Park Place

Research summary

I am interested in the (epi)genetic mechanisms underlying sex differences in brain function and behaviour. My work focusses on the role of genes on the sex chromosomes (i.e. the X and Y), which are asymmetrically inherited between the sexes: females inherit two X chromosomes (one from each parent), whereas males inherit just one X chromosome (invariably from their mother) and a Y chromosome from their father. A principal aim of my research is to elucidate why the sexes are differentially vulnerable to common and disabling disorders such as autism and ADHD, and ultimately to help develop more effective sex-specific therapies.  

Location summary

I am based in the Schools of Psychology and Medicine at Cardiff University. I am a member of the Behavioural Genetics Group (PSYCH and MEDIC), the MRC Centre for Neuropsychiatric Genetics and Genomics (PSYCH and MEDIC), the Institute of Psychological Medicine and Clinical Neurosciences (MEDIC) and the Neuroscience and Mental Health Research Institute.

Teaching summary

I have lectured on the General Psychology, Biological Psychology, and Abnormal and Clinical Psychology modules, and am an Academic Tutor and Placement supervisor. I have supervised numerous Ph.D students, Intercalated and final year research projects, and visiting scientists.  

Selected publications (2014 onwards)

 

Full list of publications

 

Research topics and related papers

1. The role of steroid sulfatase in brain and behavioural phenotypes in man and mouse

Parallel work in mice and humans has suggested that the X-linked gene STS, which encodes the neurosteroid-modulating enzyme steroid sulfatase, may influence attentional function, impulsivity and aggression. Our ongoing work in mouse models and clinical populations aims to further specify psychological processes that are sensitive to the effects of steroid sulfatase (dys)function, and to clarify the neurobiological mechanisms through which steroid sulfatase (dys)function may impinge upon cognitive processes (notably those which go awry in disorders such as Attention Deficit Hyperactivity Disorder (ADHD)). 

Trent et al (2013) Psychoneuroendocrinology 38(8):1370-80
Davies (2012) Trends in Molecular Medicine 18(5):256-62
Trent et al (2012) Neuropsychopharmacology 37(5):1267-74
Trent et al (2011) Psychoneuroendocrinology 37(2):221-9
Stergiakouli et al (2011) Genes Brain and Behavior 10(3):334-44
Davies et al (2009) Biological Psychiatry 66(4): 360-7
Davies et al (2006) Biological Psychiatry 61(12):1351-1360

2.  The identification and characterisation of brain and behavioural processes sensitive to X-linked gene dosage or X-linked imprinting

As females inherit two X chromosomes, in contrast to the male’s one, there is the possibility that some X-linked genes (i.e. those that escape X-inactivation) may be expressed more highly in female than male brain, and may influence sex-specific neurobiology. To identify processes that are sensitive to X-linked gene dosage we use a mouse model, the 39,XO mouse, which is female but which only has one X chromosome. Imprinted genes are monoallelically expressed in a parent-of-origin dependent manner; as a consequence of asymmetric inheritance of the X chromosome, X-linked imprinted genes may be expressed in a sex-specific manner. We have previously identified a novel X-linked imprinted gene in mice (Xlr3b) which may influence cognition. Our current work, in collaboration with labs in Spain and the USA, is geared towards understanding the function of Xlr3b(and other X-linked imprinted genes discovered since) in brain and heart development. This ongoing work is likely to provide insights into the cognitive and cardiac abnormalities seen in the developmental disorders Turner syndrome (resulting from X-monosomy) and autism.

Lynn et al (2007) Behavioural Brain Research 172(2): 173-182
Davies et al (2006) BioEssays 28(1):35-44
Davies et al (2005) Nature Genetics 37(6):625-629
Isles et al (2004) Human Molecular Genetics 13(17):1849-1855

3. Investigating the role of Sry in brain function and behaviour

Sry is a Y-linked (hence, male-specific) gene which encodes a transcription factor controlling the expression of a number of key developmental genes, including those involved in monoamine metabolism. During embryogenesis, Sry expression in the bipotential gonad kickstarts a signalling cascade which culminates in testes formation; the testes subsequently secrete large amounts of testosterone masculinising developing neural tissue. Sry is also expressed in the brain, and hence might also affect the function of this organ in a testosterone-independent manner. We aim to identify behavioural processes that are sensitive to Sry function (either directly or indirectly) through using mice transgenic/deleted for the Sry gene and through antisense knockdown of the gene in specific regions of the rat brain. These studies may help us understand the molecular basis of the male-bias in certain disorders of dopaminergic function such as pathological gambling and ADHD.

Kopsida et al (2013) PLOS ONE 8(8):e73699
Kopsida et al (2009) The Open Neuroendocrinology Journal 2: 20-30
Davies & Wilkinson (2006) Brain Research 1126(1):36-45

Funding

MRC New Investigator Award (£537,591 fEC) 2010-2013 ‘Characterising the behavioural and neural functions of steroid sulfatase, a newly-identified modulator of ADHD risk’ (Collaborators Dr Paul Burgoyne, MRC National Institute for Medical Research, UK, and Dr Jonathan Fry, University College London, UK)

Research Councils UK (£125,000) 2007-2012 Fellowship in Translational Research in Experimental Medicine

MRC Centre for Neuropsychiatric Genetics and Genomics Seedcorn Funding (£4,946) ‘Recruitment and genotyping of a panel of X-linked ichthyosis patients and controls’ (Collaborator Dr Paul Bowden, Cardiff University School of Medicine, UK)

Research group

Dr Simon Trent

Research collaborators

Dr Trevor HumbyProfessor Lawrence Wilkinson (Cardiff University Schools of Psychology and Medicine)
Dr Kate LangleyProfessor Anita Thapar (Cardiff University School of Medicine)
Dr Paul Burgoyne (MRC National Institute for Medical Research, London, UK)
Dr Jonathan Fry (University College London, UK)
Drs Beatriz Cubelos and Marta Nieto (Centro Nacional de Biotecnologia, Madrid, Spain)
Dr Robert Hinton (Cincinnati Children’s Hospital Medical Center, USA)

Postgraduate research interests

Males and females differ in their complement of sex-linked genes i.e. those on the X and Y chromosomes: males inherit a single X chromosome from their mother, and a Y chromosome from their father, whilst females inherit two X chromosomes, one from either parent. My work in both animal models and human populations aims to elucidate the extent and specificity with which genes on the sex chromosomes may influence neurodevelopment, brain function and behaviour, and hence, the mechanisms underlying sexually dimorphic neurobiology. As most common neuropsychiatric disorders show a sex bias in their incidence, age-at-onset, developmental course and response to therapy, these studies may have important implications for understanding why men and women are differentially vulnerable to such disorders and for developing more effective sex-specific therapies.

If you are interested in applying for a PhD, or for further information regarding my postgraduate research, please contact me directly (contact details available on the 'Overview' page), or submit a formal application here.

Previous students

Phoebe Lynn: The influence of sex-linked genetic mechanisms on brain and behaviour in mice

Eleni Kopsida: Behavioural effects of manipulations of the Y-linked Sry gene in rodents

Undergraduate education

M.Biochem (1st Class) Hon. (University of Bath)

Postgraduate education

Ph.D (Behavioural Neuroscience) (University of Cambridge)

Postgraduate Certificate in University Teaching and Learning (Module 1) (Cardiff University)

Awards/external committees

Associate Editor: Frontiers in Neurogenomics

Editorial Board member: The Open Neuroendocrinology Journal, The Scientific World Journal, World Journal of Psychiatry, World Journal of Translational Medicine

Fellow, Higher Education Academy

EMBL Workshop Fellowship

Winner, National Brain-Science Writing Prize (Researcher category)

The Florence P. Haseltine Award for Outstanding Poster Presentation, 6th Annual Sex and Gene Expression Conference, Winston-Salem, USA

British Neuroscience Association Postgraduate Prize

Oon Khye Beng Ch’hia Tsio Studentship for Preventive Medicine, Downing College, University of Cambridge

Employment

2012-present: Senior Lecturer, Cardiff University, UK

2007-2012: RCUK Fellow, Cardiff University, UK

2006-2007: Wellcome Trust ‘Value in People’ Fellow, Cardiff University, UK

2003-2006: Postdoctoral scientist, The Babraham Insitute, Cambridge, UK