The genetic architecture and functional role of the mitochondrial transcriptome in the Human Brain

Michael Devine (primary)
Clinical and Movement Neurosciences
UCL Queen Square Institute of Neurology
Alan Hodgkinson (secondary)
Medical and Molecular Genetics
King's College London

Abstract

Mitochondria play a role in many important biological processes, facilitated by the transcription of mitochondrial DNA to produce key energy-generating components. Mitochondria are particularly important in high-energy tissues such as the brain, and evidence suggests a major role for mitochondrial dysfunction in neurological disorders. Despite this, it is not understood why the consequences of mitochondrial dysfunction vary in different tissue and cell types. This project will integrate computational analysis of complex single-cell transcriptome data with functional work in cutting-edge iPSC modelling systems to answer a key question: Are aspects of mitochondrial biology specific to certain cell types of the brain?


References

Ali, A.T., Idaghdour, Y, Hodgkinson, A. (2020) Analysis of mitochondrial m1A/G RNA modification reveals links to nuclear genetic variants and associated disease processes. Communications Biology 3:147.

Ali, A.T., Boehme, L., Antona, G-C, Seitan, V.C., Small, K.S., Hodgkinson, A. (2019) Nuclear Genetic Regulation of the Human Mitochondrial Transcriptome. eLife 8:e41927.

Little, D., Luft, C., Mosaku, O., Lorvellec, M., Yao, Z., Pailluson, S., Kriston-Vizi, J., Gandhi, S., Abramov, A., Ketteler, R., Devine, M.J.*, Gissen, P.* (2018) A single cell high content assay detects mitochondrial dysfunction in iPSC-derived neurons with mutations in SNCA. Scientific Reports 8:9033. *equal contribution

Devine, M.J., Kittler, J.T. (2018) Mitochondria at the neuronal presynapse in health and disease. Nature Reviews Neuroscience 19:63-80.

Devine, M.J., Ryten, M., Vodicka, P., Thomson, A.J., Burdon, T., Houlden, H., Cavaleri, F., Nagano, M., Drummond, N.J., Taanman, J-W., Schapira, A.H., Gwinn, K., Hardy, J., Lewis, P.A., Kunath, T. (2011) Parkinson’s disease induced pluripotent stem cells with triplication of the α-synuclein locus. Nature Communications 2:440


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
GeneticsNeurobiology
Techniques & Approaches
BiochemistryBioinformaticsMicroscopy / Electrophysiology