Position Overview & Specifications
The University of Cambridge wishes to appoint a postdoctoral scientist to join Dr Michal Minczuk's research group in the MRC Mitochondrial Biology Unit in Cambridge. The postholder will work within a programme focussed on mitochondrial genome editing model and cure mitochondrial diseases.
Mammalian mitochondria contain several copies of their own genome (mtDNA) which encodes 13 essential subunits of the oxidative phosphorylation (OXPHOS) system. Pathogenic variants in the mitochondrial genome can result in mitochondrial diseases, which are a major group of inherited conditions affecting ~1 in 8,000 humans. These disorders are currently incurable and effectively untreatable, with heterogeneous penetrance, presentation and prognosis. This project aims at addressing the lack of effective treatment for these disorders.
The first goal of the project is to exploit a recently developed method for precise genome editing (DdCBE, TALED, ZFD or mitoBE - PMID: 34857922 and PMID: 34857922) to generate novel pre-clinical cellular and mouse models that recapitulate common molecular features of mtDNA disease.
The second goal is to characterise the key molecular features of these newly developed models and use them in pre-clinical treatments. In one of the approaches, we will use mitochondrial programmable nucleases (mtZFNs or mitoTALENs, PMID: 34857922) and base editors to induce specific reduction of mutant mtDNA. We will follow a reversion of mitochondrial dysfunction phenotypes using single-cell genomics, proteomics and dedicated methods assessing mitochondrial function (PMID:36827974, PMID:30250142).
The results obtained within this project will constitute proof of principle that mtDNA mutation correction using genome modification tools could provide a therapeutic route for mitochondrial diseases of diverse genetic origin. The project will be performed in close collaboration with a mitochondrial patient support and community group (CureMito.org) and an industrial partner (pretzeltx.com), increasing chances for clinical translation and commercialization of the technologies.
Candidates will have (or be about to be awarded) a PhD in biological sciences, and a track record of related research achievements. Knowledge of RNA biology and experience of structural biology are essential.
The MRC Mitochondrial Biology Unit is a world-renowned centre for research in respiratory enzymes. Additional information can be found at www.mrc-mbu.cam.ac.uk.
This is a fixed term training programme post for 3 years from date of appointment.
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Please ensure that you upload a covering letter and a CV in the Upload section of the online application. The covering letter should outline how you match the criteria for the post and why you are applying for this role. If you upload any additional documents which have not been requested, we will not be able to consider these as part of your application.
Please include details of your referees, including email address and phone number, one of which must be your most recent line manager.
The closing date for applications is: 31st July 2023
The interview date for the role is: To be confirmed
Please quote reference SM37002 on your application and in any correspondence about this vacancy.
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