Postdoctoral Fellow

Location: The Francis Crick Institute, Midland Road, London

Short summary

Dr Beale’s laboratory focuses on host pathogen interactions, particularly how cells respond to disrupted proton gradients.

Acidic pH is required for numerous physiological processes. Within a cell, Vacuolar ATPases (V-ATPases) maintain appropriate proton gradients. A defect within an acidic compartment would lead to dissipation of proton gradients. This must be detected, but how? We have shown that Components of the autophagy machinery are recruited by the V-ATPase itself. We described this process initially in response to the influenza A virus proton channel M2, but anything that challenges the cell to maintain pH gradients can give rise to this phenomenon, including viral and bacterial infection and the innate immune signalling protein STING. 

Key Responsibilities

We have recently discovered that the V1H subunit of the V-ATPase controls the recruitment of ATG16L1 (Timimi et al., BioRxiv 2023). The purpose of this role is to characterise exactly how this takes place. This is critical to our understanding of how disrupted pH gradients are sensed. To understand this fully will require structural, biochemical and cell biological approaches.

In this project, some of the specific aims include but are not limited to:

• Determining the configurations of V-ATPase that are capable of recruiting ATG16L1
• Investigating how regulation of this interaction takes place
• Determining which other interacting proteins affect the ability of V1H to recruit ATG16L1

The postholder will be responsible for:

• Driving forward this key aspect of the laboratory’s program.
• Collaborating with structural biologists within and external to the Crick.

Postdoctoral Fellows will lead their own projects, contribute to other projects on a collaborative basis (both in the lab and with external collaborators) and may guide PhD students in their research. The ability to work in a team is essential. 

About us

The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the fundamental biology underlying health and disease. Its work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative diseases.

An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London and King’s College London.

The Crick was formed in 2015, and in 2016 it moved into a new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under in one building in Europe.

The Francis Crick Institute will be world-class with a strong national role. Its distinctive vision for excellence includes commitments to collaboration; developing emerging talent and exporting it the rest of the UK; public engagement; and helping turn discoveries into treatments as quickly as possible to improve lives and strengthen the economy. 

• If you are interested in applying for this role, please apply via our website.
• The closing date for applications is 02.02.2024
• All offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom.