P22) New tools for bioconjugation using novel rearrangement reactions

About the project

About the Project Protein bioconjugation is a vital tool in modern biomedical and biotechnological research. Our groups recently established a ‘Conjugate Addition/Ring Expansion’ (CARE) approach able to selectively and irreversibly modify the N-terminus of untagged native proteins, including nanobodies for cancer cell and tissue imaging, and human chemokines, with altered downstream activation and processing following modification (Figure 1A).[1,2] Our irreversible bioconjugations are performed in water, operate under mild conditions, and in contrast to more established methods, require few equivalents of probe. In this multidisciplinary project, we will develop new, sustainable tools for bioconjugation using novel rearrangement reactions. The project spans pure organic synthesis, chemical biology, antibiotics and bacterial PROTACS. We will develop new probes designed to promote CARE-like bioconjugation, via conjugate addition with amine groups, followed by in situ rearrangement to reveal reactive functional groups for downstream modification. This will enable the late-stage installation of dual-functional probes that can be used to study and target pathogenic bacteria, bearing: i) novel macrocycles that can modulate target/host binding; and ii) handles for diversification and protein ‘tagging’ to explore cellular delivery of antibiotics and bacterial PROTACS. Supervisory Team: Prof Will Unsworth (York Chemistry), Dr Chris Spicer (York Chemistry), Prof Martin Fascione (York Chemistry), Prof Chris Schofield (Oxford Chemistry), Dr Alistair Farley (Oxford Chemistry) Key publications: [ publication 1 ] [ publication 2 ] Further information The EPSRC Centre for Doctoral Training in Chemical Synthesis for a Healthy Planet (CSHP CDT) is a EPSRC-funded centre focused on training the next generation of synthetic chemists, developing a sustainable, innovative chemistry culture that equips students to address major emerging and future global challenges in Human Health, Energy & Materials, and Food Security. We offer a fully-funded four year PhD programme, delivered jointly by the Universities of Oxford and York, comprised of taught courses and a substantive research project. Student cohorts will work together in a 4-month training period at both Oxford and York, before embarking on their main PhD projects. These substantive projects will be industry co-supervised, and based at either the Department of Chemistry in Oxford, or the Green Chemistry Centre of Excellence at York and the associated Department of Chemistry. This PhD project will primarily be based at the University of York. The first application deadline is 12 noon on the 13th November 2026 . We will continue to receive applications following this deadline, however some of the projects may be filled following the assessment of the first round of applications. We therefore encourage you to submit your application early to ensure that your first choice project is available. All project partners recognise the importance of equal participation, progression and success for all. We strive to provide a working, learning, social and living environment that will enable all our staff and students to contribute fully, to flourish and to excel - a place where we can ALL be ourselves. The Department of Chemistry in York holds an Athena SWAN Gold Award, while the Department of Chemistry in Oxford holds a Silver Award. Both are committed to supporting equality and diversity for all staff and students. The Departments strive to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel; for more details, see: Equality and Diversity at York and Equality and Diversity at Oxford . In particular, we recognise the importance of the equal participation of women at all levels in a subject that has traditionally been male-dominated. We also particularly encourage applications from people who identify as Black, Asian or from a Minority Ethnic background, who are underrepresented across the partnership. Name of supervisor/s Prof Will Unsworth (York Chemistry), Dr Chris Spicer (York Chemistry), Prof Martin Fascione (York Chemistry), Prof Chris Schofield (Oxford Chemistry), Dr Alistair Farley (Oxford Chemistry) Eligibility Criteria You must have, or expect to gain, a minimum 2:1 Honours degree or international equivalent in a subject relevant to the proposed PhD project (usually chemistry or chemical engineering, but please get in touch if you think your qualification may be relevant). Enthusiasm for research, the ability to think and work independently, excellent analytical skills and strong verbal and written communication skills are also essential requirements. Check the entry requirements for your country. English language requirements. How to apply Submit an online PhD in Chemistry application . You will need to prepare the following information: 1000-word personal statement, focusing on your interest and experience in your proposed field of research Clearly state your 1-2-3 choice of substantive research projects chosen from our list at the end of your personal statement Transcripts detailing your university-level qualifications and marks to date Two Academic/Professional References: you will be required to submit contact details for 2 referees Complete the CSHP CDT Studentship: Equality, Diversity and Inclusion (EDI) Data Form (for York applicants only). For more details on the application and selection processes, and for answers to general questions (i.e. funding eligibility, project allocation, etc.) please visit our how to apply and FAQs section or join us for our online open event . Contact Details Project-specific: Dr Will Unsworth william.unsworth@york.ac.uk , Dr Chris Spicer chris.spicer@york.ac.uk , Dr Martin Fascione martin.fascione@york.ac.uk General CDT enquiries: cshp-cdt@chem.ox.ac.uk or chem-env-pgr@york.ac.uk

Research areas