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, omics and functional (cell-based) analyses.  In addition to research, I am CGEM Post-Graduate Convenor and supervise students on Honours, MSc and PhD programmes.

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.

www.cgem.ed.ac.uk

www.igmm.ac.uk

My research aims to identify biological mechanisms underlying neurodegenerative disorders (such as dementia) and psychiatric disorders (such as depression).  We use data analytic and wet lab techniques to improve understanding at the level of the genotype, epigenome and cellular phenotype.  Examples of current projects include:

• Functional analysis of mutations in candidate genes for the above disorders, via analysis of cellular phenotypes in iPSC-derived neuronal lines that have been subjected to CRISPR/Cas9 genome editing.
• Development of a phenotype-based high throughout drug screen centred around a candidate gene for Alzheimer’s disease.
• Whole genome methylomic (and other omic) analyses of Generation Scotland, a family and population-based cohort with extensive cognitive and psychiatric phenotype data.

My goal is to uncover the biological mechanisms underlying neurodegenerative disorders (such as dementia) and psychiatric disorders (such as depression).  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.  Our work spans prediction, biomarker identification, understanding mechanisms, identifying treatment targets, and, most recently, drug discovery. 

Techniques include characterisation of the epigenome, transcriptome and proteome, in order to facilitate an unbiased assessment of potential pathogenic mechanisms, complemented by functional analyses of cellular phenotype.  I believe that integrating data-analytical and laboratory-based approaches and combining population-based and experimental datasets is a powerful strategy to address important research questions in neuroscience. 

Much of my group’s work is centred around the sortilin gene family.  This comprises five multifunctional neuronal receptors and trafficking molecules that have been implicated in both psychiatric and neurodegenerative conditions.  I am, however, interested in a wide-range of research questions pertaining to psychiatric and neurodegenerative conditions. 

My research is aimed at understanding the mechanisms underlying neurodegenerative illnesses, such as Alzheimer’s disease and psychiatric conditions, such as major depressive disorder.  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.

My group aims to further understanding of the causes of neurodegenerative disease and major mental illness by investigation of the function of the genes (and the proteins they encode) implicated in these illnesses.  For example, in one project our goals are:

1)    To understand how decreased amounts of the Alzheimer’s disease risk factor, SORLA alters the physical properties (or phenotypes) of human nerve cells.  We hypothesise that loss of SORLA will lead to differences in cell survival, morphology and/or function.

2)    To identify a phenotype (or phenotypes) that we can develop into an assay that can be assessed in a high-throughput manner.  The longer term goal is to use this high-throughput phenotype-based assay in a drug discovery screen.