Address
Form of work
SalaryAbout the role
The Gooptu Group at the University of Leicester integrates structural biology within multi-scale studies of protein misfolding, inflammation and fibrosis to define new therapeutic strategies. The role is to deliver a project using cryoEM to define the interactions between pathogenic misfolding proteins (alpha1-antitrypsin variants) and enzymes in the human endoplasmic reticulum (ER) that determine their refolding vs degradation.
We and our collaborators on this project (Roversi Group, Milan) have characterised the structures of all the relevant enzyme paralogues from an archetypal thermophilic system, and of alpha1-antitrypsin in a range of conformations, including the pathological polymer state purified ex vivo. We already have very encouraging preliminary data showing we can purify complexes of misfolding alpha1-antitrypsin states with some of these enzymes, to the point where good cryoEM datasets can be collected. The project will optimise 3D reconstruction and refinement, and undertake structural studies of the complexes with the relevant human paralogues. Once the interactions are understood, mutagenesis studies will validate key features.
The project is also supported by a PhD student for whom the successful candidate will act as bench supervisor. The work will be based within the University of Leicester Institute for Structural & Chemical Biology (LISCB) that hosts the Midlands Cryo-EM Facility.
The group is co-hosted by two institutes of research excellence: LISCB and the NIHR Leicester BRC. It is well placed for multi-modality collaborations within two new initiatives: the University’s new interdisciplinary Centre for Fibrosis Research, the East Midlands ILD Research Alliance (EMIRA). These local and regional clusters are set up to enhance current and future external collaborations for international excellence.
To discuss the project and the role further, please contact Prof Gooptu (bg129@leicester.ac.uk), who can also provide names of current and former PDRA/Fellow colleagues for separate discussions if wished.
About you
The ideal candidate will be able to understand principles of cryoEM and how these are applied in practice of data collection, processing and reconstruction. The following abiltities will be essential to the role,
- Ability to produce and characterise recombinant protein
- Ability to prepare samples for negative stain and cryoEM studies, to use EM to obtain high quality datasets and to process data to undertake single particle reconstruction of 3D volume
- Ability to demonstrate behaviours that are in accordance with the University values of inclusive, inspiring and impactful.
Additional information
Informal enquiries are welcome and should be made to Professor Bibek Gooptu on bg129@leicester.ac.uk
