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Biography

I am a Reader and Psychiatric Genomics Group Leader, at the Centre for Genomic and Experimental Medicine (CGEM) within the Institute of Genetics and Molecular Medicine (IGMM). I have a PhD and an established track record in medical genetics, genomics and functional analysis.  My PhD studentship involved cloning a breakpoint of a balanced translocation linked to schizophrenia in a large family.  Next, I moved to the Sanger Centre, where I constructed physical maps for production of the human genome sequence.  I was recruited back to the MRC HGU to lead genetic and physical mapping of a region of chromosome 4p linked to bipolar disorder in a large family.  Here I used skills and contacts from the Sanger Centre, including setting up collaborations and establishing a bioinformatics group.  The move to a Research Fellow post at what is now CGEM (and subsequent promotions) allowed me to expand the analysis of the 4p region, and my group, and to diversify into other areas of psychiatric and cognitive research.  On chromosome 4, we progressed to the definition of variants at the DNA sequence level, including development of SNP genotyping strategies, haplotype analysis, and application of LD-based, region-wide SNP genotyping, which led to significant association findings (replicated by others).  Other research areas have included association analysis of functional candidate genes, genomic imaging and more recently, the regulation of expression levels of DISC1.  Evidence for an important role of regulation of gene expression in complex disorders is mounting, and a significant part of my work is now focused here.  For example, some of my most recent expression analyses have identified links between molecules known to be involved in schizophrenia and others implicated in autism (featured on http://www.schizophreniaforum.org/ and http://sfari.org/).  We have also recently analysed differential methylation in the large bipolar disorder family, and have a larger-scale study in progress.  Another major research focus has arisen from the recent affordability of whole genome sequencing, and builds on both my bioinformatics experience and previous work.  We are sequencing members of the family, which has necessitated the development of a novel bioinformatics pipeline to investigate the possible impact of regulatory variants.   Other work in my group focuses on molecular and functional analysis of variants in the family and, in parallel, we have a programme to produce induced pluripotent stem cells (iPSCs). 

 

In addition to research, I am CGEM Post-Graduate Convenor.  I organise the Neuroscience Honours Neurogenetics Module and teach students on MSc and PhD programmes (including bioinformatics tutorials).  I have supervised five students as principal supervisor and six as assistant supervisor.  I have examined four PhD theses and acted as non-examining Chair for one thesis.  I am an Associate Member of CCACE, a Faculty Member of “Faculty of 1000” and sit on the Faculty of 1000 Research Editorial Board, the IGMM Postgraduate Studies Committee and the IGMM Computation and Bioinformatics Advisory Group. 

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

IdentifIcation and investigation of genes and variants for psychiatric illness

Research Interests

Our research is aimed at understanding the mechanisms underlying susceptibility to major mental illness, including schizophrenia, bipolar disorder, major depressive disorder and autism.  Psychiatric illness 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 major mental illness, 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, the less-than-perfect concordance in monozygotic twins also suggests an important role for environmental factors in pathogenesis. 

 

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

  • What are the genes & 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 level key to disease susceptibility?
  • What is the role of epigenetics in disease development?
  • Can we use this knowledge to develop biomarkers and improved drug treatments for illness?

 

Our research involves analysis of biological samples from individuals with major mental illness, both from pedigrees with a high incidence of psychiatric illness, and from a population-based biobank, Generation Scotland.  Generation Scotland allows linkage of: medical data from NHS records; DNA sequence; functional measurements, such as gene expression levels; socio-economic data; cognitive and personality test data.

 

Our research is focussed on the following areas:

 

Identification of variants responsible for illness

  • We are carrying out whole-genome sequence analysis of a pedigree with multiple cases of bipolar disorder and major depressive disorder
  • This involves the development of new methods, for example, for the identification of functional variants from sequence data

 

Investigation of biological mechanisms underlying illness

  • We are investigating the effect of variants in candidate genes
  • In addition, we are carrying out functional analysis of candidate genes in model systems, including induced pluripotent stem cells (iPSCs)

 

Examining the role of altered expression in psychiatric illness

•        We are investigating altered expression of protein coding genes and miRNAs in patient samples

 

Epigenetic analysis

•        We are analysing epigenetic modifications in patient samples compared to those from control individuals

My research in a nutshell

Our research is aimed at understanding why some people develop major mental illness, such as schizophrenia, bipolar disorder, major depressive disorder and autism.  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.

 

Psychiatric illness is an area where research has much to offer.  These illnesses 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 psychiatric illlness?
  • What is the role of the environment in disease development?
  • Can we use all of 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?

 

We are using state-of-the-art techniques to investigate genes, proteins and cells from patients to try and answer these questions.  These methods include technology that i) determines the sequence of all of the genes of an individual, so we can find changes that underlie illness and ii) changes skin cells into brain cells (neurons) so we can study how patient cells differ from control cells in a dish.

Highlighted research outputs

  1. The DISC1 promoter: characterisation and regulation by FOXP2

    Research output: Contribution to journalArticle

  2. The effects of a neuregulin 1 variant on white matter density and integrity

    Research output: Contribution to journalArticle

  3. The DNA sequence of the human X chromosome

    Research output: Contribution to journalArticle

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