PhD Studentship: Structure and function of tyrosine fusion kinases in leukaemia and their regulation by the HSP90 molecular chaperone

A PhD studentship (3.5 years) is available from September 2025 under the supervision of Dr Jasmeen Oberoi, Genome Damage and Stability Centre, University of Sussex.

Deadline: 2^nd May 2025

Brief Description of the Project:

Tyrosine kinases are essential for normal cellular function and growth. Their function is normally tightly controlled in the cell. Chromosomal translocations can lead to tyrosine kinase genes becoming fused to fragments of other genes, resulting in ‘Tyrosine fusion kinase’ proteins. These fusion kinases, which are found in haematological malignancies and solid tumours, instead drive uncontrolled growth of cancer cells. They subsequently serve as biomarkers and therapeutic targets for these cancers.

The Heat Shock Protein 90 (HSP90) molecular chaperone is emerging as an important regulator of fusion kinase activity and stability. Inhibition of HSP90 activity, promotes degradation of these oncogenic kinases. The aims of this project are to understand the structural mechanisms by which these large fusion kinases assemble into cancer-driving forms, and associate with the HSP90 molecular chaperone system. The student will take a multidisciplinary approach, using structural biology techniques (cryoEM and X-ray crystallography) to determine the structures of tyrosine fusion kinases found in leukaemia, and their complexes with the HSP90 molecular chaperone. Biochemistry and biophysical methods will be used to probe how the fusion kinases assemble into their oligomeric, active forms and interact with the HSP90 molecular chaperone system. New allosteric approaches to disrupt these protein assemblies and inhibit fusion kinase function will be further investigated in leukaemia cells. The use of Tyrosine Kinase Inhibitors (TKIs) in the treatment of tyrosine fusion kinase driven cancers is limited by intolerance, drug resistance and disease relapse. Therefore, there is a need to identify alternative strategies towards targeting the function of these tyrosine fusion kinases for these patients.

This project would suit a candidate with a background in Biochemistry, Molecular Biology or Structural Biology and an interest in cancer signalling or molecular chaperones. The project will be based in the Genome Damage and Stability Centre (GDSC), a University Centre of Excellence, with access to state-of-the art facilities and a vibrant network of cancer researchers. There will also be opportunities to participate in conferences and undertake technical and career development skills training.

Informal enquiries about the project are welcome and can be made to:

Dr Jasmeen Oberoi at j.oberoi@sussex.ac.uk.                       

How to apply:

Please submit a formal application by clicking the 'Apply' button, above, attaching a CV, degree transcripts and certificates, and two academic referees. A research proposal is not required. Instead, please upload a personal statement describing your subject areas of interest, skills and previous experience, motivation for Doctoral Research, future goals, and why you are applying to this project.

On the application system select Programme of Study – PhD Genome Stability. Please select ‘funding obtained’ and state the supervisor’s name where required. Applicants with overseas fee status need to provide evidence showing how they will fund the difference between Home and International tuition fees (approx. £20k per year).

Candidates should have or expect to obtain a minimum 2:1 undergraduate degree. An MSc degree will be advantageous. Your qualification should be in Biochemistry, Structural biology or a related subject area. You may also be considered for the position if you have other professional qualifications or experience of equivalent standing.

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