Centre for Genomic & Experimental Medicine
Centre for Genomic & Experimental Medicine

Kirsty Millar Research Group

Identifying potential disease pathways in psychiatry through investigation of the effects of a t(1;11) translocation linked to major mental illness

Section: Medical Genetics 

K.Millar
Dr Kirsty Millar - Group Leader

Research in a Nutshell

Inheritance of a t(1;11) chromosomal translocation substantially increases the risk of developing schizophrenia, bipolar disorder or recurrent depression in a single large family. This translocation represents a rare example of a definitively causal genetic event in psychiatry, and therefore provides a valuable opportunity to identify molecular pathways underlying major mental illness. To achieve this we are working with neural precursor cells and neurons derived by the induced pluripotent stem cell route from several members of the family, both translocation carriers and non-carriers. These neural cells are being used to examine differential gene expression patterns between carriers and non-carriers, with the aim of identifying mechanisms that are altered by the translocation. The translocation directly disrupts a gene called DISC1 that is essential for many processes in the developing and adult brain. Another research area is study of the emerging function of DISC1 in regulation of cargo transport within neuronal axons and dendrites. We use time-lapse imaging of live neurons to study movement of fluorescently-labelled cargo. This technique has demonstrated that DISC1 and several of its protein binding partners regulate directional movement of mitochondria, a mechanism that is critical for neurotransmission in the brain. We are now investigating regulation of neuronal transport of other cargo by DISC1.

Research Programme: Identifying potential disease pathways in psychiatry through investigation of the effects of a t(1;11) translocation linked to major mental illness.

 

K.Millar group

People

Dr Kirsty Millar Group Leader
Helen Torrance Research Assistant
Jonathan Phillips Research Assistant
Laura Murphy PhD student
Marion Bonneau PhD student
Shane O’Sullivan PhD student

Contact

kirsty.millar@ed.ac.uk

Collaborations

  • Neil Carragher, Institute of Genetics & Molecular Medicine
  • Siddharthan Chandran, University of Edinburgh
  • Kathy Evans, Centre for Genomics and Experimental Medicine
  • Philippe Gautier, Institute of Genetics & Molecular Medicine
  • Michel Didier, Sanofi 
  • Andrew McIntosh, University of Edinburgh
  • David Price, University of Edinburgh
  • Pippa Thomson, Centre for Genomics and Experimental Medicine

Partners and Funders

  • Brain & Behavior Research Foundation (NARSAD)
  • European Union Seventh Framework Programme ‘Deciphering inter- and intracellular signalling in schizophrenia (IN-SENS, www.in-sens.eu/)
  • Wellcome Trust
  • Medical Research Council
  • Bequest from Eva Lester
  • Moray Foundation

Scientific Themes

Identifying potential disease pathways in psychiatry through study of a t(1;11) translocation that co-segregates with major mental illness; modelling psychiatric illness using t(1;11) family-derived induced pluripotent stem cells, neural precursors and neurons; functional studies of the DISC1 gene that is disrupted by the t(1;11) translocation; the influence of DISC1 upon neuronal intracellular trafficking of mitochondria and other cargo

Technology Expertise

Production, culture and analysis of induced pluripotent stem cells, neural precursors and neurons; time-lapse live neuronal imaging of motile cargo, three-dimensional Structured Illumination Microscopy (3D-SIM)