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University of Cambridge
Cambridge, United Kingdom
Department: MRC Toxicology Unit
Closing date: 18 November 2020
The Medical Research Council Toxicology Unit is an internationally renowned institution focused on the delivery of field-changing mechanistic insights into toxicology and disease.
The Unit is equipped with state-of-the-art facilities including Cryo-EM, super resolution microscopy, mass spectrometry and offers excellent opportunities for researcher development.
The Unit is part of the University of Cambridge and will physically relocate to the Gleeson Building, Central Cambridge in Nov 2020.
We are looking to appoint an MRC Fellow (PF) to work in the laboratories of Prof. Marion MacFarlane to carry out research into the ‘Molecular Mechanisms of Cell Death’.
Our laboratory is focused on investigating cell death pathways that are regulated in response to members of the TNF cytokine family and agents that trigger mitochondrial-dependent cell death, with a specific emphasis on mechanisms that regulate activation of cell death signalling complexes.
The aim of the project is to obtain novel insights on the regulation and 3D molecular architecture of key multiprotein signalling complexes that direct cell death/survival.
This is a three-year training and development position for a postdoc who has recently completed their doctoral studies, is moving into a new research discipline or has limited experience of key transferable skills.
We support scientists in these positions with a range of formal and on-the-job training to ensure you receive the training relevant to your role and identify additional training to help support your future career.
- The successful candidate will have a higher degree (PhD) in a relevant discipline and experience in protein expression in mammalian systems and purification of protein complexes for analysis of protein structure and function.
- Experience in Cryo-Electron Microscopy and subsequent structural analysis is desirable.
- The ability to publish high quality research;
- To be able to work both independently and as part of a team, together with excellent communication and problem solving/critical thinking skills are essential.
Further information on the Toxicology Unit can be found at: https://www.mrc-tox.cam.ac.uk/
This project offers the exciting opportunity to integrate biochemical & structural biology approaches to enable characterisation of large macromolecular complexes and obtain novel insights on the regulation and molecular architecture of multiprotein signalling complexes that direct cell fate.
We have pioneered the reconstitution of cell death signalling complexes, including the Death-Inducing Signalling Complex (DISC), and now wish to determine the overall 3D architecture of these large macromolecular assemblies and ultimately their structure.
Importantly, the Unit has an FEI Talos 200C Cryo-Electron Microscope and is a partner in the Midlands Regional Cryo-EM Facility which is equipped with an FEI Titan Krios 300 kV Cryo-Electron Microscope.
The following publications have direct relevance to this project:
– Horn et al. Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-KB Activation and Cell Survival. Cell Reports, 2017.
– Hughes et al. Co-operative and Hierarchical Binding of c-FLIP and Caspase-8: A Unified Model Defines How c-FLIP Isoforms Differentially Control Cell Fate. Molecular Cell, 2016.
– Dickens et al. A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Molecular Cell, 2012.