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Structural studies of the bacterial type II secretion system


Project Description

A QMUL Principal’s Postgraduate Research Studentship is available in the group of Professor Richard Pickersgill, starting in September 2019.

The type II secretion system spans the two membranes and periplasm of the Gram-negative bacterial cell wall and secretes toxins causing disease and death. We are working to determine how this molecular machine works and provide a pathway to new antibiotics. The most likely mechanism is that a short pilus is assembled to push the toxin through the pore in the outer-membrane (the secretin).

Questions:
The inner-membrane proteins form the assembly platform that build this pilus, but how does the inner-membrane complex assemble a pilus? How is substrate recognised? How is assembly switched on and off in response to recognition of the substrate? And, is rotation involved in the pilus assembly process?

Our competitive advantage:
We have a competitive advantage in imaging for the first time both the inner-membrane complex and the entire cell wall spanning secretion system.

Training in electron microscopy:
In this project you will learn how to produce and purify membrane proteins. You will learn how to prepare grids for cryo-electron microscopy. You be trained in electron microscope and single particle image analysis producing structures of components and the intact type II secretion system. You may also get involved in other techniques in structural biology.

Environment and support:
We are research-led Russell Group University with a strong structural biology group. You will generate date for high-quality publications and make use of state of the art equipment. We have a recently installed a cryo-EM machine for screening and have access to the LonCEM, Diamond and other microscopes for high-resolution data collection.

Eligibility and Applying

Applications are invited from candidates with, or expecting to be awarded, a first or an upper-second class bachelors degree (or equivalent qualification) in biochemistry (or similar). An MSc in an appropriate subject may be an advantage. Applicants from outside of the UK are required to provide evidence of their English language ability. Please see our entry requirements page for details: https://www.qmul.ac.uk/sbcs/postgraduate/phd-programmes/entry-requirements/

Informal enquiries about the project can be sent to Professor Richard Pickersgill (). Formal applications should be submitted online by the stated deadline.

Funding Notes

The studentship is open to applicants of any nationality. It will cover tuition fees and provide an annual tax-free maintenance allowance for 3 years at the Research Council rate (£17,009 in 2019/20).

References

[1] Gu S, Vladimir VE, Shaw R et al.(2017). The role of intrinsic disorder and dynamics in the assembly and function of the type II secretion system. BBA - Proteins and Proteomics
10.1016/j.bbapap.2017.07.006
[2] Rehman S, Gu S, Shevchik VE et al.(2013). Anatomy of secretin binding to the Dickeya dadantii type II secretion system pilotin. Acta Crystallogr D Biol Crystallogr vol. 69, (Pt 8) 1381-1386.
10.1107/S0907444913007658
[3] Gu S, Kelly G, Wang X et al.(2012). Solution structure of homology region (HR) domain of type II secretion system. J Biol Chem vol. 287, (12) 9072-9080.
10.1074/jbc.M111.300624

How good is research at Queen Mary University of London in Biological Sciences?

FTE Category A staff submitted: 23.39

Research output data provided by the Research Excellence Framework (REF)

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