In this project the postdoctoral researcher will use Drosophila and mouse models of mitochondrial disease to investigate how mitochondrial metabolism contributes to neuronal dysfunction and neurodegeneration. Mitochondrial dysfunction plays a critical role in neurodegenerative diseases, including mitochondrial diseases, Alzheimer's and Parkinson's disease. Mitochondrial dysfunction triggers mitochondrial stress signalling pathways. Dr Bateman's lab has developed Drosophila models of mitochondrial stress signalling in neurons. Our studies have shown that activation of mitochondrial stress signalling modifies neuronal function (Cagin et al. 2015, PNAS; Duncan et al., 2018 PLoS Genetics; Hunt et al., 2019 J Cell Biol). This project will study how mitochondrial stress signalling alters the levels of metabolites called polyamines in the brain to contribute to pathology in mitochondrial disease.
The researcher will use a combination of metabolomic and transcriptional analyses of a Drosophila model of mitochondrial disease to understand how mitochondrial stress signalling alters polyamine metabolism in the brain. State-of-the-art genetic and imaging techniques, combined with functional assays, will be used to understand the mechanism by which polyamine metabolism contributes to neuropathology. The researcher will then test whether modulating polyamine levels alleviates the neurological phenotypes in Drosophila and mouse mitochondrial disease models. This project will lead to a greatly improved understanding of the molecular basis of mitochondrial disease and the pre-clinical validation of potential new treatment to prevent neurodegeneration.
The researcher will be supervised by and be part of Dr Joseph Bateman's lab.
Dr Bateman's lab is in the Department of Basic and Clinical Neuroscience, housed in the Maurice Wohl Clinical Neuroscience Institute, a state of the art research facility on the Denmark Hill campus at King's College London, housing 150 clinicians and scientists from disciplines including neuroimaging, neurology, psychiatry, genetics, molecular, cellular biology and drug discovery. The Bateman lab shares space with 4 other groups (Vagnoni, Hirth, Fanto, and Sreedharan groups) all studying nervous system function and degeneration using Drosophila and mouse models, making this an exciting and dynamic research environment.
The project incorporates ongoing collaborations with Dr Cathy Fernandes, at the Social, Genetic and Developmental Psychiatry (SGDP) Centre, King's College London, and Professor Navdeep Chandel at Northwestern University, Chicago, USA.
The project is funded by the Medical Research Council.
More details on the Bateman lab are here:https://www.batemanlab.org/
More details on the Department of Basic and Clinical Neuroscience, King's College London, are here: https://www.kcl.ac.uk/neuroscience/about/departments/basic-clinical-neuroscience
Essential criteria
Desirable criteria
https://jobs.kcl.ac.uk/gb/en/job/015764/Research-Associate-Department-of-Basic-Clinical-
Dr Joseph Bateman, 020 7848 8144 / joseph_matthew.bateman@kcl.ac.uk
Please note that this is a PhD level role but candidates who have submitted their thesis and are awaiting award of their PhDs will be considered. In these circumstances the appointment will be made at Grade 5, spine point 30 with the title of Research Assistant. Upon confirmation of the award of the PhD, the job title will become Research Associate and the salary will increase to Grade 6.
