In this project the research associate 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 have 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.
You 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. You 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.
You will be supervised by and be part of Prof Joseph Bateman’s lab.
Prof 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
This post will be offered on a fixed-term contract up to the 31st May 2024 with the possibility of a further extension.
This is a full-time post - 100% full time equivalent
• Contribute to the research project, by studying the role of mitochondrial metabolism in neuronal dysfunction and neurodegeneration.
• Perform behavioral, biochemical and immunohistochemical analyses of Drosophila models.
• Perform metabolomic analyses of Drosophila models.
• Perform behavioral and immunohistochemical analyses of mouse models.
• Perform experiments independently, and in collaboration with others, keeping accurate and comprehensive records throughout.
• Take a leading role in the development of new laboratory techniques and assist and train other members of the group, including students and other research staff, in the application of these techniques in related lab projects.
• Supervise technical staff and students engaged in related research under the direction of the group leader.
• Keep up to date with the relevant scientific literature.
• Lead discussions on literature at group journal club meetings.
• Collate and prepare the data of research studies as stated above for publication in peer reviewed scientific journals.
• Present research findings and papers at internal and external academic meetings, seminars and conferences and to contribute to the internal and external visibility of the laboratory.
• To be pro-active in communicating with collaborating laboratories, including liaising with collaborators and developing new ideas to progress the project.
• To assist with the general running of the laboratory as directed.
• Facilitate collaboration and networking which engages and supports the activities of this research.
• Participate in educational activities as appropriate to the stage of your career.
• To be committed to your own personal career development.
The above list of responsibilities may not be exhaustive, and the post holder will be required to undertake such tasks and responsibilities as may reasonably be expected within the scope and grading of the post.
Skills, knowledge, and experience
1. Degree or equivalent in a relevant scientific field.
2. PhD awarded in relevant scientific field, or PhD in relevant scientific field near completion.
- Knowledge of molecular basis of neurodegenerative diseases.
- Knowledge of mitochondrial biology.
- Experience in Drosophila genetics.
- Experience in metabolomics.
- Experience in mouse genetics.
- Experience in confocal imaging.