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School of Biological and Behavioural Sciences

Dissecting the role of MCE proteins for thylakoid membrane lipid homeostasis

Project Overview

Cyanobacteria are ancient photosynthetic prokaryotes and the prokaryotic ancestors of plant chloroplasts. They have a specialised extensive internal membrane thylakoid system hosting the photosynthetic machinery. Photosynthesis is tightly linked to lipid homeostasis in the thylakoid membrane. Lipid trafficking and its role in membrane lipid homeostasis is poorly understood. MCE proteins are the conserved substrate binding proteins of lipid ABC transporters, found in all diderm bacteria and in eukaryotic chloroplasts. They are important for membrane lipid homeostasis under stress conditions (1). Although some proteobacterial MCE complex structures are known, their stimuli for function, substrate specificity, interaction networks etc are still unknown. Using the model cyanobacterium Synechococcus elongatus and an integrated structural cell biology approach, the Darbari and Mullineaux labs are interested in dissecting the mechanism of action of the MCE complex for their role in thylakoid membrane integrity and function. Recently a previous joint CSC-funded PhD student characterised a phenotype for MCE protein knockout in the model organism, affecting the thylakoid membrane under specific growth conditions. This project extends that work and aims to characterise the effect of ATP binding/hydrolysis and channel mutations for lipid transit in the MCE complex on thylakoid membrane under specific growth conditions that affect thylakoid membrane assembly/disassembly (2). The project will further characterise protein-protein interactions using proximity labelling, immuno-pulldowns, biochemical and structural studies to explore links between lipid trafficking via MCE complex and lipid metabolism. 

Research Environment

The Darbari group have expertise in membrane protein biochemistry, structural biology and structural bioinformatics with excellent access to X-ray crystallography and TEM facilities including High-resolution Cryo-transmission electron microscopy as part of LonCEM. The Mullineaux group work on photosynthesis and cell biology in cyanobacteria, using a combination of molecular genetics, biochemistry, spectroscopy and advanced fluorescence microscopy, including confocal and super-resolution (SIM2) microscopy. Training in all these techniques will be available to the PhD student. The groups have been working together to probe the mechanisms of lipid trafficking in cyanobacteria.

Find out more about the School of Biological and Behavioural Sciences on our website.

Keywords: ABC transporters, lipid trafficking, membrane proteins, thylakoid membrane, structural biology, molecular cell biology

Entry Requirements

We are looking for candidates to have or expecting to receive a first or upper-second class honours degree and a Master’s degree in an area relevant to the project such as Biochemistry, Microbiology, Structural Biology or Molecular Cell Biology.

Knowledge of protein biochemistry, molecular biology techniques & structural biology would be highly advantageous but are not required.

You must meet the IELTS requirements for your course and upload evidence before CSC’s application deadline, ideally by 1st March 2025. You are therefore strongly advised to sit an approved English Language test as soon as possible, where your IELTS test must still be valid when you enrol for the programme.

Please find further details on our English Language requirements page.

How to Apply

Formal applications must be submitted through our online form by 29th January 2025 for consideration. Please identify yourself as a ‘CSC Scholar’ in the funding section of the application.

Applicants are required to submit the following documents:

  • Your CV
  • Personal Statement
  • Evidence of English Language e.g.) IELTS Certificate
  • Copies of academic transcripts and degree certificates
  • References

Find out more about our application process on our SBBS website.

Informal enquiries about the project can be sent to Dr Vidya Darbari AT v.darbari@qmul.ac.uk Admissions-related queries can be sent to sbbs-pgadmissions@qmul.ac.uk

Shortlisted applicants will be invited for a formal interview by the supervisor. If you are successful in your QMUL application, then you will be issued an QMUL Offer Letter, conditional on securing a CSC scholarship along with academic conditions still required to meet our entry requirements.

Once applicants have obtained their QMUL Offer Letter, they should then apply to CSC for the scholarship with the support of the supervisor.

For further information, please go to the QMUL China Scholarship Council webpage.

Apply Online

References

  1. Fenn, K., Wong, C. T., & Darbari, V. C. (2020). Mycobacterium tuberculosis uses Mce proteins to interfere with host cell signaling. Frontiers in molecular biosciences, 6, 149
  2. Huokko T, Ni T, Dykes GF, Simpson DM, Brownridge P, Conradi FD, Beynon RJ, Nixon PJ, Mullineaux CW, Zhang P, Liu L-N (2021) Probing the biogenesis pathway and dynamics of thylakoid membranes. Nat Commun 12:3475
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