PhD Studentship in Cell and Molecular Biosciences - Elucidating the assembly mechanism of the Tat protein export machinery

Number of awards:

1

Start date and duration:

23 September 2019 for 3 years.

Overview:

The twin arginine protein transport (Tat) system is a conserved and highly unusual protein transport pathway that exports folded proteins across the cytoplasmic membranes of bacteria. It is required for the virulence of most important human pathogens and secretes a number of critical virulence factors. The aim of this PhD project is to determine fundamental information on the mechanism of Tat transport by elucidating details about the organisation of the Tat receptor complex and how it is activated upon binding of substrates.

The Tat system is highly unusual because it transports folded proteins. Current evidence suggests that the active Tat translocase assembles ‘on demand’ upon interaction with a substrate protein, and that it disassembles once translocation is complete. The E. coli Tat machinery comprises the TatA, TatB and TatC membrane proteins. When a Tat substrate binds to the TatABC receptor, this causes conformational changes in the receptor resulting in the recruitment of tens of further TatA molecules. The assembled oligomer of TatA forms the transmembrane translocation pathway, and following passage of substrate across the membrane, the assembled translocation system dissociates to the resting state.

The project has two main aims:

1. To map the signal peptide binding site within the Tat receptor and to determine whether binding of the signal peptide at this site is dependent on the protonmotive force;

2. To determine whether a newly-discovered TatA/B binding site on TatC is essential for operation of the Tat pathway.

The project will involve a mix of genetics, biochemistry, in vivo crosslinking and molecular modelling.

Sponsor:

Newcastle University (https://bit.ly/2TV5U6P)

Name of supervisor(s)

Professor Tracy Palmer (https://bit.ly/2AzV519), Institute for Cell and Molecular Biosciences (https://bit.ly/2DR9hWH)

Eligibility Criteria:

You must have, or expect to achieve, at least a 2:1 Honours degree in biochemistry, microbiology or a related area. A further qualification such as an MSc or MRes is advantageous.

This award is available to UK/EU and international applicants.

To study this course you need to meet the following English Language requirements:

IELTS 6.5 overall (with a minimum of 5.5 in all other sub-skills).

How to apply:

You must apply through the University’s online postgraduate application system. To do this please ‘Create a new account’ (https://bit.ly/2AxLpnD).

Only mandatory fields need to be completed. However, you will need to include the following information:

insert the programme code 8300F in the programme of study section
select ‘PhD in the Faculty of Medical Sciences (full time) – Cell and Molecular Biosciences as the programme of study
insert the studentship code CB151 in the studentship/partnership reference field
attach a covering letter and CV. The covering letter must state the title of the studentship, quote the studentship reference code CB151 and state how your interests and experience relate to the project
attach degree transcripts and certificates and, if English is not your first language, a copy of your English language qualifications.