Funding
Funded
Development of “beyond cysteine” chemical probes and focused screening libraries
School of Chemistry and Chemical Engineering | PHD
Reference Number
SCCE-2025-011
Application Deadline
14 March 2025
Start Date
1 October 2025
Overview
Irreversible covalent inhibitors that target nucleophilic cysteine residues on disease-relevant POIs are well established with multiple covalent therapeutics in clinical use against targets such as Bruton’s tyrosine kinase (BTK) and epidermal growth factor receptor (EGFR). Much of the focus of recent targeted covalent inhibitor (TCI) research has centred around targeting reactive cysteine residues with much success as noted above. Given that cysteine has a relatively low proteome-wide abundance across potential binding sites and its high intrinsic nucleophilicity (leading to potential off-target toxicities) there is an emerging interest in developing complementary “beyond cysteine” approaches aimed at targeting other nucleophilic amino acid residues such as histidine, lysine and serine. This, it is believed will vastly expand the targetable proteome leading to next generation TCIs that can overcome resistance mechanisms (common with current TCIs) as well as offering new avenues for treating diseases of high unmet need.
The project will focus on the design, synthesis and validation of next generation “beyond cysteine” activity-based protein profiling probes (ABPPs) and focused electrophile screening libraries. Cysteine-targeting ABPPs are well established for use in chemoproteomic cysteine ligandability and screening exercises, however ABPPs targeting side-chain residues such as histidine and lysine are less well developed.
New ABPPs and focussed electrophile libraries will be developed and validated in collaboration with the newly established QUB/NI Chemoproteomic Centre-of-Excellence. Work within the McLaughlin group at QUB has established several new chemotypes with embedded electrophilic functionality, whose reactivity towards nucleophilic residues can be modulated through the modification of inherent electronic parameters. Several molecular scaffolds have been identified, based on ongoing work within the McLaughlin Lab, with distinct but complimentary reactivity profiles, each of these has the potential for wide ranging application in this area.
This approach differs from the current state-of-the-art as the molecular scaffolds have increased “3D-ness”, which is commonly under-represented in current screening libraries. Key to the successful implementation of this strategy will be the development of robust chemistries for the synthesis of each unique electrophilic motif, which will be the central objective of the project. Once chemistries have been developed the project team will evaluate the novel electrophilic molecules against non-cysteine residues (histidine/lysine etc) in relevant biophysical and biological assays.
Funding Information
This project is funded via QUB’s Enhanced Postgraduate Skills Doctoral Training Programme(EPS DTP) with industrial sponsorship from Almac. Almac Group is a global leader in providing a range of expert services and support across the drug development lifecycle.
UK studentships - cover tuition fees and include a maintenance stipend of £19,237 per annum.
This project offers an additional top-up stipend of £5,000 per year, and together with the maintenance stipend will give a take home pay of £24,237 per annum.
An industry gross salary (pre-tax, student loan repayment, pension (3%) and national insurance contributions) of £32,000 results in an approximately equivalent take home pay.
A UK studentship is open to UK and ROI nationals, and to EU nationals with settled status in the UK, subject to meeting specific nationality and residency criteria.
DfE studentship eligibility information can be viewed at: https://www.economy-ni.gov.uk/publications/student-finance-postgraduate-studentships-terms-and-conditions
Project Summary
Supervisor
Dr Mark McLaughlin
Mode of Study
Full-time: 4 years
Funding Body
QUB EPS DTP
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
-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 OpportunitiesFind PhD opportunities and funded studentships by subject area.
2.Funded Doctoral Training ProgrammesWe 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 loansThe 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 ScholarshipsInformation on Postgraduate Research scholarships for international students.
Funding and Scholarships
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