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New tools for new antibiotic targets – The development of novel probes for mechanistic studies on bacterial glycolipid-processing enzymes

School of Chemistry and Chemical Engineering | PHD

Applications are now CLOSED
Funding
Funded
Reference Number
SCCE-2023-004
Application Deadline
21 April 2023
Start Date
2 October 2023

Overview

In 2019 antimicrobial resistance (AMR) killed more people than breast cancer, HIV and malaria. Addressing AMR is a real-world need (QUB Strategy 2030). Bacteria produce many different glycopolymers that are vital to their survival, including peptidoglycan, which is a key component of the bacterial cell wall required for structural integrity, and lipopolysaccharide (LPS), which protects Gram-negative bacteria from bile salts and lipophilic antibiotics. The bacterial cell wall is targeted by many clinically used antibiotics, including penicillin, vancomycin and fosfomycin. Peptidoglycan and LPS biosynthesis involve several key glycolipid intermediates, all of which are linked to the cell membrane by the universal lipid carrier, undecaprenyl phosphate. The enzymes that process undecaprenyl-containing biomolecules are hot antibiotic targets, as they are unique to bacteria and absolutely essential to their growth. In particular, a class of enzymes called flippases, which transport some undecaprenyl-linked biomolecules across cell membranes, may be the Achilles heel of bacteria as they are a bottleneck in glycopolymer syntheses. However, detailed studies on these enzymes have been limited due to a lack of suitable probes to interrogate their mechanism of action. An understanding of enzyme mechanism is a vital pre-requisite to the rationale design of inhibitors.

This project has two main objectives: 1) to develop novel high-throughput assays for flippases that allow mechanistic studies and inhibitor screens to be performed; and 2) to develop substrate mimics that can be co-crystallized with flippases. This is a highly interdisciplinary project. Natural product isolation, the chemical synthesis of glycolipid probes and enzymatic assays will be performed in the Cochrane Lab. Protein expression and the growth of protein crystals and protein/glycolipid co-crystals will be performed along with collaborators in the Caffrey Lab at Trinity College Dublin. The student will also complete a 3 month internship at the Swiss Lightsource in the Paul Scherrer Institut (Switzerland) macromolecular X-ray crystallography.

Funding Information

The studentship is jointly funded by industry and DfE and is open to UK and ROI nationals (with residency conditions), or EU nationals that have obtained settled status in the UK. Full eligibility and stipend information can be viewed via: https://www.nidirect.gov.uk/articles/department-economy-postgraduate-studentship-scheme

Project Summary
Supervisor

Professor Stephen Cochrane


Mode of Study

Full-time: 3 years


Funding Body
DfE CAST Award
Apply now Register your interest

Chemistry overview

The School of Chemistry and Chemical Engineering aims to promote sustainable processes and materials to meet the energy and healthcare demands of the future. The School is expanding rapidly and this is creating many new and exciting research opportunities with over £15m being invested to develop and expand the core research areas of catalysis, biological and medicinal chemistry, and materials.

Mode of study / duration

Registration is on a full-time or part-time basis, under the direction of a supervisory team appointed by the University. You will be expected to submit your thesis at the end of three years of full-time registration for PhD, or two years for MPhil (or part-time equivalent).

Key Facts

QUB is a member of the Russell Group of the UK’s 24 leading research-intensive universities.

  • QUB is ranked =13th in the UK for research intensity
    QUB is ranked 9th in the UK for Graduate Prospects – Outcomes (Complete University Guide 2025)
  • Over 99% of Queen’s research environment was assessed as world-leading or internationally excellent in REF2021
    88% of research submitted by Queen’s has been assessed as world-leading or internationally excellent in REF2021
  • 83% of Research Impact case studies by the School has been assessed as world-leading or internationally excellent REF2021, placing it among the top UK universities for Research Impact

Course content

Research Information

Associated Research
Much of our research falls under the broad headings of Healthcare and Sustainability, examples of recent funded projects include development of novel antibiotics and reduction of single use plastics. The School also leads the EU-funded Bryden Centre for renewable energy research, the industry-led Centre for Advanced Sustainable Energy (CASE) as well as our world-leading QUILL ionic liquids research centre. Students trained in our School are equipped with the skills that allow them to go out and make a real difference in the world.

Our areas of interest include adventurous research at the cutting edge of catalysis (where chemistry meets other disciplines, especially engineering, innovative Molecular Materials and Functional Materials), ionic liquid technology (‘super solvents' which do not form vapours and can be used as non-polluting alternatives to conventional solvents) and Synthesis and Biological Organic Chemistry (working to deliver compounds addressing the regulation of cellular functions).
QUILL (Queen's University Ionic Liquid Laboratories): the largest multidisciplinary research group in the world centred on ionic liquid technology, whose work on ‘super solvents' (which do not form vapours and can be used as non-polluting alternatives to conventional solvents) was voted ‘Most Important British Innovation of the 21st Century' in 2013.
All of our research groups have significant links with researchers and other institutions globally, and there are opportunities for collaboration and study visits, etc.
We have extensive links with industry, meaning that employment prospects for our graduates are excellent.
Much of our research is interdisciplinary, and our students can broaden their experience and knowledge by working with researchers from other disciplines (eg biologists, physicists).

Career Prospects

Introduction
For further information on career opportunities at PhD level please contact the Faculty of Engineering and Physical Sciences Student Recruitment Team on askEPS@qub.ac.uk. Our advisors - in consultation with the School - will be happy to provide further information on your research area, possible career prospects and your research application.

People teaching you

Professor John Holbrey
Director of Postgraduates
Chemistry&Chemical Engineering
Email: J.Holbrey@qub.ac.uk

Course structure
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Entrance requirements

Graduate
The minimum academic requirement for admission to a research degree programme is normally an Upper Second Class Honours degree from a UK or ROI HE provider, or an equivalent qualification acceptable to the University. Further information can be obtained by contacting the School.

International Students

For information on international qualification equivalents, please check the specific information for your country.

English Language Requirements

Evidence of an IELTS* score of 6.0, with not less than 5.5 in any component, or an equivalent qualification acceptable to the University is required (*taken within the last 2 years).

International students wishing to apply to Queen's University Belfast (and for whom English is not their first language), must be able to demonstrate their proficiency in English in order to benefit fully from their course of study or research. Non-EEA nationals must also satisfy UK Visas and Immigration (UKVI) immigration requirements for English language for visa purposes.

For more information on English Language requirements for EEA and non-EEA nationals see: www.qub.ac.uk/EnglishLanguageReqs.

If you need to improve your English language skills before you enter this degree programme, INTO Queen's University Belfast offers a range of English language courses. These intensive and flexible courses are designed to improve your English ability for admission to this degree.

Tuition Fees

Northern Ireland (NI) 1 TBC
Republic of Ireland (ROI) 2 TBC
England, Scotland or Wales (GB) 1 TBC
EU Other 3 £25,600
International £25,600

1 EU citizens in the EU Settlement Scheme, with settled or pre-settled status, are expected to be charged the NI or GB tuition fee based on where they are ordinarily resident, however this is provisional and subject to the publication of the Northern Ireland Assembly Student Fees Regulations. Students who are ROI nationals resident in GB are expected to be charged the GB fee, however this is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.

2 It is expected that EU students who are ROI nationals resident in ROI will be eligible for NI tuition fees. The tuition fee set out above is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.

3 EU Other students (excludes Republic of Ireland nationals living in GB, NI or ROI) are charged tuition fees in line with international fees.

All tuition fees quoted are for the academic year 2021-22, and relate to a single year of study unless stated otherwise. Tuition fees will be subject to an annual inflationary increase, unless explicitly stated otherwise.

More information on postgraduate tuition fees.

Chemistry costs

Additional course costs

All Students

Depending on the programme of study, there may also be other extra costs which are not covered by tuition fees, which students will need to consider when planning their studies . Students can borrow books and access online learning resources from any Queen's library. If students wish to purchase recommended texts, rather than borrow them from the University Library, prices per text can range from £30 to £100. Students should also budget between £30 to £100 per year for photocopying, memory sticks and printing charges. Students may wish to consider purchasing an electronic device; costs will vary depending on the specification of the model chosen. There are also additional charges for graduation ceremonies, and library fines. In undertaking a research project students may incur costs associated with transport and/or materials, and there will also be additional costs for printing and binding the thesis. There may also be individually tailored research project expenses and students should consult directly with the School for further information.

Bench fees

Some research programmes incur an additional annual charge on top of the tuition fees, often referred to as a bench fee. Bench fees are charged when a programme (or a specific project) incurs extra costs such as those involved with specialist laboratory or field work. If you are required to pay bench fees they will be detailed on your offer letter. If you have any questions about Bench Fees these should be raised with your School at the application stage. Please note that, if you are being funded you will need to ensure your sponsor is aware of and has agreed to fund these additional costs before accepting your place.

How do I fund my study?

1.PhD Opportunities

Find PhD opportunities and funded studentships by subject area.

2.Funded Doctoral Training Programmes

We offer numerous opportunities for funded doctoral study in a world-class research environment. Our centres and partnerships, aim to seek out and nurture outstanding postgraduate research students, and provide targeted training and skills development.

3.PhD loans

The Government offers doctoral loans of up to £26,445 for PhDs and equivalent postgraduate research programmes for English- or Welsh-resident UK and EU students.

4.International Scholarships

Information on Postgraduate Research scholarships for international students.

Funding and Scholarships

The Funding & Scholarship Finder helps prospective and current students find funding to help cover costs towards a whole range of study related expenses.

How to Apply

Apply using our online Postgraduate Applications Portal and follow the step-by-step instructions on how to apply.

Find a supervisor

If you're interested in a particular project, we suggest you contact the relevant academic before you apply, to introduce yourself and ask questions.

To find a potential supervisor aligned with your area of interest, or if you are unsure of who to contact, look through the staff profiles linked here.

You might be asked to provide a short outline of your proposal to help us identify potential supervisors.

Download Postgraduate Prospectus