Overview
Allosteric regulation of enzymes involves ligands binding to sites other than the active site, causing a structural change that alters the enzyme’s function. Recent advances in cryo-electron microscopy (cryo-EM) using time-resolved methods have enabled visualisation of multiple structural states of enzymes during allosteric regulation. This PhD project combines time-resolved cryo-EM, biochemical and biophysical techniques to capture structural snapshots in the allosteric regulation of methylenetetrahydrofolate reductase (MTHFR), a folate metabolising enzyme with implications in cancer and neurological diseases.
The student will carry out cryo-EM imaging of human MTHFR titrated with its native allosteric inhibitor S-adenosyl-l-methionine (SAM) at different time points, to capture the multi-step structural transition between the enzyme’s inhibited and active states. This will be complemented by activity assays, binding assays and structure-guided mutagenesis, to decipher the molecular mechanism of SAM-mediated inhibition.
This studentship is aligned with the Molecular Sciences for Medicine (MoSMed) Centre for Doctoral Training (CDT), as part of MoSMed2.
Eligibility Criteria
Please see the MoSMed website for further details regarding academic eligibility.
The studentship covers fees at the Home rate (UK and EU applicants with pre-settled/settled status and meet the residency criteria). International applicants are welcome to apply but will be required to cover the difference between Home and International fees.
International applicants may require an ATAS (Academic Technology Approval Scheme) clearance certificate prior to obtaining their visa and to study on this programme.
How To Apply
You must apply through the University’s Apply to Newcastle Portal
Once registered select ‘Create a Postgraduate Application’.
Use ‘Course Search’ to identify your programme of study:
· search for the ‘Course Title’ using the programme code: 8420F
· Select ‘PhD Biosciences (full time)’ as the programme of study.
· We welcome applicants who wish to undertake their studies part time. To do so, please instead select ‘PhD Biosciences (part time)’ as the programme of study and 8420P as the programme code.
You will then need to provide the following information in the ‘Further Details’ section:
· a ‘Personal Statement’ (this is a mandatory field) – upload a document or write a statement directly in to the application form. Please include the full title of the studentship, the studentship code (mos2_04), and how your interests/experience relate to the project.
· the relevant studentship code (mos2_04) in the ‘Studentship/Partnership Reference’ field. You must include the relevant code for your application to be considered.
· when prompted for how you are providing your research proposal – select ‘Write Proposal’. You should then type in the title of this project. You do not need to upload a research proposal.
In the ‘Supporting Documentation’ section please upload:
· An up-to-date CV.
Please upload all documents in PDF format.
You must submit one application per studentship, you cannot apply for multiple studentships on one application.
Contact Details
