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School of Biological and Behavioural Sciences

Designer MCE proteins: Unity and diversity of lipid transport function in double membranes

Research environment

The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2021 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 180 PhD students working on projects in the biological and psychological sciences. Our students have access to a variety of research facilities supported by experienced staff, as well as a range of student support services.

The successful applicant will enter a vibrant research environment, under the supervision of Dr Vidya C. Darbari and Dr Christoph Engl. Both labs are well equipped to carry out all the molecular biology, biochemistry and biophysical experiments with excellent access to X-ray crystallography and TEM facilities including High-resolution Cryo-transmission electron microscopy as part of LonCEM. For details see: https://www.qmul.ac.uk/sbcs/staff/vidyadarbari.html and https://www.qmul.ac.uk/sbbs/staff/christophengl.html 

Training and development

Our PhD students become part of Queen Mary’s Doctoral College which provides training and development opportunities, advice on funding, and financial support for research. Our students also have access to a Researcher Development Programme designed to help recognise and develop key skills and attributes needed to effectively manage research, and to prepare and plan for the next stages of their career.

The PhD project is interdisciplinary and spans microbiology, molecular biology, biophysics, biochemistry and structural biology. The student will be trained in core skills related to these specific disciplines, which will ensure the student gains depths of knowledge in these areas. Both groups use a broad range of approaches and have diverse research teams, which will also ensure the student gains breadth of knowledge through working in highly multidisciplinary teams. The overall skills obtained through this project will enable the student to address the major global challenges in their future career with a focus on Anti microbial resistance in this project. 

Project description

Membranes of diderm bacteria are the first line of defence, essential for survival in harsh environments and crucial for stress response. Mammalian Cell entry (MCE) proteins play a vital role in maintaining membrane integrity in unfavourable environments, probable role in membrane biogenesis, for assimilating lipids as nutrient sources in mycobacteria and probable host immune modulatory roles in intracellular pathogenic bacteria. They assemble into ABC lipid transporter in various double membranes of distinct lipid compositions. Structure function relationship will aid small molecule designs for antimicrobials and lipid transport modulators for biotechnology applications such as biofuels and sterol assimilation. Although proteobacterial MCE protein structures are characterised (MlaD, PqiB and YebT/LetB (LetB: Lipophilic envelope spanning tunnel B), the mechanism for lipid substrate specificity and the unified role of MCE proteins in stress response is not understood.

This project aims to understand the specific role of MCE domains for substrate specificity and link to membrane integrity and membrane functions using structural biology and microbial cell biology. To understand if substrate specificity is gated by MCE domains and how lipid binding specific to MCE domain affects membrane functions, we will create various MCE domain chimeras using MCE domains from mycobacteria or cyanobacteria that probably transport varied lipids. Alphafold multimer will be used to aid the design for the chimeric constructs and in silico substrate docking and binding studies carried out to investigate lipid specificity.  Functional mutations that disrupt lipid binding will also be investigated. Complementation studies will be carried out to do detailed microbial phenotypic analysis to understand the specific role of MCE domains.  Interesting MCE constructs will be taken forward for both lipid binding studies and structural studies using CryoEM.

Funding

This studentship is open to students applying for CONACyT funding. CONACyT will provide a contribution towards your tuition fees each year and Queen Mary will waive the remaining fee. CONACyT will pay a stipend towards living costs to its scholars. Further information can be found here: https://conacyt.mx/convocatorias/convocatorias-becas-al-extranjero/

Eligibility and applying

Please refer to the CONACyT website here: https://conacyt.mx/convocatorias/convocatorias-becas-al-extranjero/ for full details on eligibility and conditions on the scholarship. 

Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree in Biochemistry . A masters degree is highly desirable, but not essential. 

Applicants from outside of the UK are required to provide evidence of their English language ability. Please see our English language requirements page for details: https://www.qmul.ac.uk/international-students/englishlanguagerequirements/postgraduateresearch/ 

Informal enquiries about the project can be sent to Dr Vidya Chandran Darbari at v.darbari@qmul.ac.uk 

Applicants will need to complete an online application form by this date to be considered, including a CV, personal statement and qualifications. Shortlisted applicants will be invited for a formal interview by the project supervisor. Those who are successful in their application for our PhD programme will be issued with an offer letter which is conditional on securing a CONACyT scholarship (as well as any academic conditions still required to meet our entry requirements).

Once applicants have obtained their offer letter from Queen Mary they should then apply to CONACyT for the scholarship as per their requirements and deadlines, with the support of the project supervisor.

Only applicants who are successful in their application to CONACyT can be issued an unconditional offer and enrol on our PhD programme.

Apply Online

References

  1. Fenn K, Wong CT, Darbari VC. Mycobacterium tuberculosis Uses Mce Proteins to Interfere With Host Cell Signaling. Front Mol Biosci. 2020 Jan 8;6:149. doi: 10.3389/fmolb.2019.00149. PMID: 31998747; PMCID: PMC6961568.
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