Discovering the hidden control switches in human metabolic enzymes - allostery

Supervisors: Prof Wyatt Yue, Prof Celine Cano, Dr Kate Harris

Date: Wednesday, May 20, 2026

Competition Funded PhD Project (UK Students Only)

About the Project

Why this project matters

Enzymes do not just switch “on” or “off” at their active sites. Many have hidden, sophisticated dimmer switches - allosteric sites - elsewhere on the protein often far away from the action. When a small molecule binds to allosteric sites, the enzyme can subtly change shape, turning its activity up or down, without directly contacting the active site. These allosteric switches are increasingly recognised as important regulators of metabolism. Because allosteric sites are often unique to each enzyme, they also represent promising and advantageous drug targets offering better selectivity and safety.

Our research group is interested in discovering new allosteric sites on metabolic enzymes that play key roles in ageing, neurological diseases, and cancer. The challenge is that many allosteric sites are hidden – they become visible only when the right molecule comes along. Using x-ray crystallography to screen for small molecules, we discovered previously unknown pockets on two different metabolic enzymes – galactokinase and glycolate oxidase. Some are located close to the active site exerting more localised changes, whereas others are surprisingly distant from the active site and require long-range shape changes.

What will the research look like

Our discoveries open exciting questions about how different types of remote/nearby allosteric switches operate at the molecular level. This project combines cutting-edge complementary approaches of biochemical assays, structural techniques, and computational tools, to address this question.

You will explore how small molecules binding to the allosteric site influence enzyme activity, interactions between proteins, and cellular behaviour (chemical biology). You will visualise how enzymes change shapes by capturing specific states using x-ray crystallography and cryo-electron microscopy (structural biology). You will also model enzyme motions and trace how structural changes travel from allosteric site to active site (molecular dynamics).

Why this is exciting

This project offers a unique opportunity to investigate allosteric enzyme regulation from both experimental and computational angles, using non-conventional technologies that are proven tractable. You will work at the intersection of biochemistry, chemistry, and medicine - fields that increasingly rely on one another to drive new therapeutic advances – by conducting the research in three highly-collaborative research labs. You will uncover new paradigms of enzyme regulation, and validate brand-new drug targets to tackle metabolic disorders of unmet need.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.

HOW TO APPLY

Please complete the following application form – Google Form

Applicants can only apply for 1 project; any additional applications will not be accepted.

Applicants should send the following documents to FMSstudentships@newcastle.ac.uk:

• a CV (including contact details of at least two academic (or other relevant) referees).
• a Cover letter – stating your project choice, as well as including additional information you feel is pertinent to your application.
• copies of your relevant undergraduate degree transcripts and certificates.
• a copy of your IELTS or TOEFL English language certificate (where required)
• a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE

Please submit your documents in the following format only:

• each document should be submitted as a separate attachment and should be named as follows: candidate surname, candidate name – document type. For example: Jones, Jamie – CV; Jones, Jamie – cover letter.
• Please submit .pdf documents where possible for your CV, cover letter, transcripts and certificates. Do not submit photos of certificates.
• Do not combine documents into one pdf. You may zip separate documents into a zip file to send via email if required.
• When emailing your application, please use the email subject header: FMS PhD Application 2026

Applications not meeting these criteria may be rejected.

Informal enquiries may be made to the lead supervisor of the project you are interested in.

The deadline for all applications is 12 noon BST (UK time) on Wednesday 20th May 2026.