IESR4 UEDIN Mitochondrial effects of abnormal DISC1 expression
One ESR Marie Curie training position is available at the University of Edinburgh Centre for Genomic and Experimental Medicine in the team of Dr Kirsty Millar.
We are investigating a promising genetic risk factor for major mental illness, DISC1, as part of our drive to understand the molecular mechanisms underlying psychiatric disorders. Mitochondria appear to be extremely sensitive to the effects of DISC1 mutations, with putative disease-associated mutations leading to abnormal mitochondrial aggregation and trafficking deficits (Eykelenboom et al, Hum Mol Genet 21: 3374-86, 2012, Ogawa et al, Hum Mol Genet Epub 2013). Such defects are likely to deleteriously affect neuronal function, and may lead to elevated risk of psychiatric illness. This PhD project will investigate mitochondrial effects of a balanced t(1;11) translocation that directly disrupts the DISC1 gene, and substantially increases risk of developing schizophrenia, bipolar disorder or depression in a large Scottish family (Blackwood et al, Am J Hum Genet 69: 428-33 2001). We have developed a panel of induced pluripotent stem cells from t(1;11) carriers and their relatives. These will be differentiated to produce neurons for analysis of mitochondrial function, focussing upon mitochondrial aggregation/mitophagy pathways. Several techniques will be utilised including neuronal differentiation and viral transduction, confocal fluorescence microscopy, and various protein analysis methodologies including immunoblotting and immunoprecipitation.
The project is embedded in collaborations with several European and U.S. laboratories and is part of a European Graduate School on molecular psychiatry with close collaborations and training in collaborating laboratories.
Please contact Dr Kirsty Millar for further details (firstname.lastname@example.org).
Nr of positions available : 1
Neurosciences - Neurobiology
Early stage researcher or 0-4 yrs (Post graduate)
First Stage Researcher (R1)
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