Dissecting the role of Mammalian Cell entry proteins in Mycobacterium tuberculosis.
The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2014 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 150 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. The lab is 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.
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 student will use and gain expertise in structural techniques for determining high-resolution structures including X-ray crystallography and/or Cryo-Transmission Electron Microscopy. A range of biochemical and biophysical techniques will be employed for substrate binding characterisation. Molecular biology and microscopy techniques for cellular localisation will also be employed.
Tuberculosis (TB) is one of the top ten causes of mortality worldwide claiming ~1.5 million lives and reported 5.8 million new cases in 2020. Mycobacterium tuberculosis (Mtb), the causative pathogen is predominantly an intracellular organism that can survive within host macrophages for prolonged durations by subverting host cell immune response and utilising nutrients such as fatty acids/sterols from host cell membranes. Mammalian cell entry (Mce) proteins are virulence factors necessary for intracellular survival of Mtb. Mce proteins (24 in Mtb) are encoded in four different mce operons each minimally expressing two membrane permease subunits (YrbEA/B) and six Mce (A-F) proteins that assemble to form a ABC lipid transporter powered by a common ATPase MceG.
The Mce proteins have been proposed ancillary functions for host immune modulation, maintaining cell wall integrity and mutations affecting multidrug resistance. Mce proteins are characterised by the conserved Mce/MlaD domain ubiquitous in diderm bacteria and chloroplast. Although structures of Mce/MlaD proteins in Gram negative bacteria have been recently determined, this does not explain the architecture of mycobacterial Mce transporter, or mechanism for lipid import or modulation of host signalling pathways.
The aim of this project is to characterise the architecture and mechanism of action of Mce4 proteins to illuminate substrate recognition and transit and extend this understanding to other Mce transport systems. This will also highlight the structural determinants for mycomembrane spanning proteins and ultimately aid strategies for diagnostics and prevention using extracellular epitopes and structure guided drug discovery.
This studentship is open to students applying for China Scholarship Council funding. Queen Mary University of London has partnered with the China Scholarship Council (CSC) to offer a joint scholarship programme to enable Chinese students to study for a PhD programme at Queen Mary. Under the scheme, Queen Mary will provide scholarships to cover all tuition fees, whilst the CSC will provide living expenses for 4 years and one return flight ticket to successful applicants.
Eligibility and applying
- Be Chinese students with a strong academic background.
- Students must hold a PR Chinese passport.
- Applicants can either be resident in China at the time of application or studying overseas.
- Students with prior experience of studying overseas (including in the UK) are eligible to apply. Chinese QMUL graduates/Masters’ students are therefore eligible for the scheme.
Please refer to the CSC website for full details on eligibility and conditions on the scholarship.
Applications are invited from candidates with, or expecting to be awarded, at least an upper-second class bachelors degree, or equivalent qualification, in Biochemistry. A masters degree is desirable, but not essential.
Applicants are required to provide evidence of their English language ability. Please see our English language requirements page for details.
The deadline for applications to Queen Mary is 30th January 2022. 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 CSC 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 CSC for the scholarship by the advertised deadline with the support of the project supervisor. For September 2022 entry, applicants must complete the CSC application on the CSC website between 10th March - 31st March 2022.
Only applicants who are successful in their application to CSC can be issued an unconditional offer and enrol on our PhD programme.
- Fenn, K. Wong, C. T., Darbari, V. C. Mycobacterium tuberculosis Uses Mce Proteins to Interfere With Host Cell Signaling. Front Mol Biosci
(2020) 6:149. doi: 10.3389/fmolb.2019.00149. eCollection 2019.