Dr William Davies

Senior Lecturer

Research group:
Neuroscience
Email:
DaviesW4@cardiff.ac.uk
Telephone:
029 208 70152
 
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. Principal aims of my research are: a) to understand why the sexes are differentially vulnerable to common and disabling developmental disorders such as autism and ADHD, b) to understand the pathophysiology underlying psychological disorders associated with pregnancy and childbirth, and c) to help develop more effective sex-specific therapies.

Location summary

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

Teaching summary

I currently lecture on the Biological Psychology, Behavioural Genetics and The Scientific Basis of Psychological Medicine (MEDIC) modules, and have previously lectured on the General Psychology and Abnormal and Clinical Psychology modules. I am an Academic Tutor and have supervised numerous Ph.D students, Intercalated B.Sc in Psychology (MEDIC) and final year research projects, and visiting scientists.

Selected publications (2014 onwards)

 

Full list of publications

 

Research topics and related papers

Our work employs a wide variety of experimental techniques including: operant and spontaneous assays of behaviour in rodents, anatomical and biochemical analysis of body tissues, assays of gene and protein expression, measurement of endocrine markers, genetic modification and genetic analysis, neuropsychological testing, and online survey approaches. 

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

Our previous work in mice and humans has suggested that the X-linked gene STS, which encodes the neurosteroid-modulating enzyme steroid sulfatase, may influence a wide range of cognitive and behavioural functions, notably attention. Ongoing work in rodent 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. This work is of direct relevance to the rare disorder X-linked ichthyosis (caused by steroid sulfatase deficiency), and may also shed light upon the mechanisms underlying idiopathic developmental disorders.  

Malik et al. (2017) Journal of Medical Case Reports (in press)
Humby et al. (2017) Brain and Behavior 7(3):e00646
Chatterjee et al. (2016) PloS ONE 11(10):e0164417
Davies et al. (2014) Neuropsychopharmacology (2014) 39(11):2622-32
Trent et al. (2014) Molecular Autism. 2014 5(1):21
Trent et al (2013) Psychoneuroendocrinology 38(8):1370-80
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

2.  Genetic and endocrine mechanisms underlying sex differences in brain development, behaviour and physiology

Females inherit two X chromosomes (one from each parent) whereas males inherit a single X chromosome (invariably from their mother) and a Y chromosome from their father. This asymmetry of inheritance across the genders gives rise to three main genetic mechanisms that could either underpin male-female differences in physiology directly, or via effects on hormones including androgens and oestrogens: i) expression of Y-linked genes in males only (including the testis-determining gene SRY), ii) higher expression of X-linked genes which escape X-inactivation in female tissues, and iii) differential expression of X-linked genes that are subject to the epigenetically-mediated process of genomic imprinting. Our collaborative work, in rodent models (e.g. 39,XO mouse and Four Core Genotypes model), in clinical populations, and in healthy participants and tissues aims to investigate the extent and specificity with which each of these three mechanisms contributes to sex differences in physiology. This work is likely to inform our understanding of the molecular pathophysiology underlying sex chromosome aneuploidies such as Turner and Klinefelter syndromes, and sex-biased developmental disorders such as ADHD and autism.  

Richards et al. (2017) Early Human Development 112:14-19
Green et al. (2017) Journal of Neurodevelopmental Disorders 9:25
Hinton.et al. (2015) Journal of Cardiovascular Development and Disease 2(3):190-199
Davies (2014) Front Neuroendocrinol. 35(3):331-46
Kopsida et al (2013) PLOS ONE 8(8):e73699
Davies (2013) Brain Research Bulletin 92:12-20
Trent & Davies (2012) Biological Psychology 89(1):1-13
Kopsida et al (2009) The Open Neuroendocrinology Journal 2: 20-30
Lynn et al (2007) Behavioural Brain Research 172(2): 173-182
Davies et al (2007) Biological Psychiatry 61(12):1351-1360
Davies et al (2006) BioEssays 28(1):35-44
Davies & Wilkinson (2006) Brain Research 1126(1):36-45
Davies et al (2005) Nature Genetics 37(6):625-629
Isles et al (2004) Human Molecular Genetics 13(17):1849-1855

3. Understanding the biological basis of postpartum psychosis risk

New mothers can be affected by a number of psychiatric conditions which range in severity and prevalence. We are particularly interested in postpartum psychosis (PP), a rare but extremely serious psychiatric disorder affecting mothers shortly after childbirth and characterised by delusions, mood swings, anxiety and cognitive disorganisation. Despite its severity, the neurobiology underpinning PP risk is very poorly-understood, partially as a consequence of not having suitable animal models available. Our work in rodent models and clinical populations aims to identify and characterise plausible biological risk pathways for PP, ultimately with a view to developing better treatments and predictive biomarkers.

Davies (2017) World Journal of Psychiatry 7(2):77-88
Humby et al. (2016) Psychoneuroendocrinology 74:363-370
Davies (2012) Trends in Molecular Medicine 18(5):256-62

4. Developing rodent tasks of cognition: understanding sex differences in gambling behaviour

We have developed a number of new operant tasks to assess cognition in rodents, many of which are analogues of neuropsychological tasks used to assess cognition in humans, and several of which have now been adapted for use with touchscreen apparatus to allow sophisticated stimulus presentation. We are currently interested in using these tasks to understand the biological basis of gambling predisposition, and in particular, to understand why the prevalence of gambling behaviour, and the progression to pathological gambling, differs between males and females.

Humby et al. (2013) Neuropsychopharmacology 38(11):2150-9
Van den Bos et al. (2013) Neuroscience and Biobehavioral Reviews 37(10):2454-71
Humby et al. (1999) European Journal of Neuroscience 11(8):2813-23

5. Testing new genetic rodent models of psychiatric disorder: the impact of sex

I am co-supervisor or Ph.D mentor for numerous projects examining the behavioural and cognitive effects of manipulating genetic risk loci for psychiatric disorders (notably ZNF804A/Zfp804a, Cyfip1, Fmr1, Setd1a and Cacna1c) in rodent models; I am particularly interested in whether these manipulations give rise to sex-specific effects and whether they can shine a light upon biological mechanisms which act to mediate the ‘female protective effect’ against developmental disorders.

Funding

MRC Centre for Neuropsychiatric Genetics and Genomics Co-PI (£3.4M)

Wellcome Trust Integrative Neuroscience Ph.D scheme Co-PI (£2.3M)

MRC New Investigator Research Award (£430K)

Research Councils UK Fellowship in Translational Research in Experimental Medicine (£125K)

MRC Centre for Neuropsychiatric Genetics and Genomics and Neuroscience and Mental Health Research Institute Seedcorn Funding (£10K)

Research group

I work closely with the other PIs within the Behavioural Genetics Group at Cardiff University (http://sites.cardiff.ac.uk/behavioural-genetics/), and supervise, co-supervise and mentor, numerous graduate and undergraduate students within this group.

Research collaborators

Dr Trevor Humby and Professor Lawrence Wilkinson (Cardiff University, UK)
Professor Paola Dazzan and Dr Monserrat Fuste-Boadella (Institute of Psychiatry, Psychology and Neuroscience, Kings College London, UK)
Dr Gareth Richards (University of Cambridge, UK)
Dr James Turner and Mr Obah Ojarikre (Crick Institute, UK)
Dr Tamar Green (Stanford University, USA)
Dr Wafaa Eyaid (King Abdullah International Medical Research Center, Saudi Arabia)
Professor Dan Rujescu (University of Halle, Germany)
Dr Tommaso Cassano (University of Foggia, Italy)

Postgraduate research interests

We are interested in how, and why, the genders differ in terms of their behaviour and in their vulnerability to different psychological conditions. We are especially interested in understanding the biological mechanisms underpinning risk of developmental disorders such as ADHD and autism (which are diagnosed far more frequently in males than females) and pregnancy and childbirth-related psychiatric disorders such as postpartum psychosis, which affects women shortly after childbirth.

We use a wide variety of experimental approaches in rodent models and in healthy and clinical human populations, and focus particularly upon the brain and behavioural effects of genes on the sex chromosomes (i.e. the X and Y) which are asymmetrically inherited between males and females.

These studies may have important implications for understanding why men and women behave differently, for why the genders are differentially vulnerable to certain 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) Hons. (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: Endocrinology, World Journal of Psychiatry, World Journal of Translational Medicine

British Council Biological and Medical Sciences Review Panel member

Genetics Society Cardiff University representative

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