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Structural analysis of the Legionella pneumophila type IV secretion system by single particle cryo-electron microscopy.

  • Full or part time
  • Application Deadline
    Tuesday, January 01, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

A 3.5-year MRC funded PhD studentship is available to work in the laboratory of Dr Tiago Costa, in the Centre for Molecular Bacteriology and Infection (CMBI) at Imperial College London. The successful applicant will be joining an internationally-renowned Research Centre, within one of the world’s top research universities.

Legionella pneumophila, (the causative agent of Legionnaires’ disease) developed a specialized type IV secretion system (T4SS), to transport >300 toxins, into host cells (Costa et al, Nat Rev Micro, 2015). Some of the characterized translocated toxins play a critical role in hijacking host cellular pathways to establish the intracellular niche where the bacteria survive, replicate and ultimately cause disease.
The goal of the project is to investigate the atomic structure of the L. pneumophila T4SS using cutting-edge single particle cryo-electron microscopy (cryo-EM) (Costa et al, Methods in Molecular Biology, 2017). The near-atomic details obtained from the 3D structure will provide unique insights into how toxins are recruited by the secretion system, how is the secretion system gated, and which is the toxins route within the secretion system. The project will pave the way for rational design of drugs that will abolish toxin secretion preventing bacterial survival and disease.

The project will provide training in the biochemical isolation and characterization of large membrane protein complexes, cutting-edge single particle cryo-EM data collection and processing (Costa et al, Cell, 2016). This work will take advantage of the state-of-the-art electron microscopy infrastructures located at the Francis Crick Institute and Diamond Light Source.

Funding Notes

The studentship covers tuition fees and provides a tax-free stipend of £18,000 per year.

Candidates should have a strong background in protein biochemistry and an interest in bacterial secretion systems. Prior experience with cryo-electron microscopy is desirable but not essential.
Candidates must have a first class or upper second class Honours degree in biological sciences (or other appropriate science subject), and a Master’s degree or equivalent research experience in a relevant subject area. Only UK or EU nationals who have been resident in the UK for the last 3 years are eligible.



References

To apply, please send a copy of your CV, and covering letter describing why you are suitable for this PhD studentship to Nicola Tingley ([email protected]).
Informal enquires can be sent to Dr. Tiago Costa ([email protected]).

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