Edinburgh Research Explorer
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Phone: 0131 651 8747

Willingness to take Ph.D. students: Yes

Biography

Following my PhD I moved to a postdoctoral post at the Wellcome Trust Sanger Institute, where I was involved in the Human Genome Project.  I was recruited back to the MRC HGU to lead the genetic and physical mapping of a genomic region linked to bipolar disorder in a large family.  Since moving to the University of Edinburgh, to what is now CGEM, my research has diversified, mainly to other areas of psychiatric and dementia research.  Ongoing work in my group spans genetics, epigenetics, bioinformatics and functional (cell-based) analyses.  In addition to research, I am CGEM Post-Graduate Convenor and teach students on MSc and PhD programmes.

Qualifications

Degree

1986 – 1990: The University of Edinburgh.

2i BSc (Hons) Biological Sciences (Genetics).

 

PhD

1990 – 1994: The University of Edinburgh /MRC Human Genetics Unit, Edinburgh.

Mapping a balanced translocation t(1:11)(q42.2;q21) linked to schizophrenia.

My PhD studentship formed part of a project that aimed to map and clone the breakpoints of a balanced translocation that is associated with schizophrenia and other major mental illness.

Websites

www.cgem.ed.ac.uk

www.igmm.ac.uk

Current Research Interests

My research aims to identify biological mechanisms underlying neuropsychiatric disorders and related traits, including bipolar disorder, major depressive disorder and Alzheimer's disease.  We use bioinformatic, data analytic and wet lab techniques to improve understanding at the level of the genotype, epigenome and cellular phenotype.  Examples of current projects include:

  • Whole genome methylation analysis of Generation Scotland, a family and population-based cohort with extensive cognitive and psychiatric phenotype data.
  • Characterisation of iPSC-derived neurons from affected and unaffected members of a family with affective disorder
  • Functional analysis of mutations in candidate genes for the above disorders, via analysis of cellular phenotypes in neuronal lines subjected to CRISPR/Cas9 genome editing.

Research Interests

My research aims to uncover biological mechanisms underlying neuropsychiatric disorders and related traits, including bipolar disorder, major depressive disorder and Alzheimer's disease.  This is an area where research has much to offer: these conditions are common; highly disabling; disease mechanisms are poorly understood and current treatment is inadequate.   

There is a clear genetic component to these conditions, as demonstrated by family, twin and adoption studies.  Identification of the genetic variants and pathways responsible for disease susceptibility is, however, still in its infancy.  In addition, it is also clear that the environment plays an important role in pathogenesis.

My group aims to further understanding of the causes of neuropsychiatric disorders and related traits by addressing the following research questions:

  • What are the genes and biological pathways responsible for susceptibility to illness?
  • What does functional investigation of the genes and pathways tell us about cellular mechanisms?
  • Is variation in gene expression levels involved in disease susceptibility?
  • What is the role of epigenetics in disease development?
  • Can we use this knowledge to develop biomarkers and, in the future, improved drug treatments for illness?

We take a multi-faceted approach, utilising bioinformatic, data analytic and wet lab techniques to improve understanding of neuropsychiatric disorders at the level of the genotype, epigenome and cellular phenotype.  Multiple complementary strands of research exist within the group, including the assessment of case-control cohorts, the characterisation of neurons made from patients’ iPSC cells and the investigation of candidate genes by genome editing.  A common aspect to all of these research strands is the use of various ‘omics techniques, that is, characterisation of the epigenome, transcriptome and proteome, in order to facilitate an unbiased assessment of potential pathogenic mechanisms.  These approaches are complemented by functional analyses of cellular phenotype, which are, in part, guided by the results of the omics analyses.

My research in a nutshell

Our research is aimed at understanding why some people develop neuropsychiatric illness, such as bipolar disorder, major depressive disorder and Alzheimer’s disease.  Our research programme is dependent upon the involvement of patient volunteers, as well as people who have provided biological samples and other data for research purposes by volunteering through Generation Scotland, a family and population-based research resource.

 

Neuropsychiatric illness is an area where research has much to offer.  These conditions are severe, common, poorly understood and inadequately treated.  While we don’t know the causes, we do know that all of these conditions have a strong genetic (inherited) component, as well as being influenced by the environment.

 

Our group aims to further understanding of the causes of major mental illness by addressing the following research questions:

  • Can we identify the genes and proteins (which are produced from genes) that are involved in susceptibility to illness?
  • Is variation in the amount of protein produced by some genes an important factor in predisposing an individual to illness?
  • What does investigation of the function of these genes and proteins tell us about how development and function of the brain can go wrong and result in neuropsychiatric illness?
  • What is the role of the environment in disease development?
  • Once we have answers to these questions, can we use this knowledge to develop 1) tests that can be used to diagnose patients and assess whether treatments are working and 2) better drug treatments for illness?

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