About the Project
T cell-based immunotherapy has revolutionised the treatment of many different types of cancer. However, to date, these treatments have not been successful or widely used for the treatment of brain tumours. The rare disease NF2 schwannomatosis (NF2-SWN) is characterised by the development of various different types of tumours within the skull, including vestibular schwannoma, meningioma and ependymomas. These tumours cause substantial suffering, limit the quality of life of patients, and can be fatal. At present there are currently no treatments that effectively target all the different types of tumour that form in a patient at the same time.
In this project the student will dissect the nature of the T cell compartment within NF2-SWN-related brain tumours. Working within clinicians, neurosurgeons and basic neuroimmunologists within the Geoffrey Jefferson Brain Research Centre, the student will employ high dimensional imaging and phenotyping approaches to reveal the core signatures of the T cells within the different tumours, focussing on the effector, memory and exhaustion programmes exhibited by the cells. The student will also utilise existing transcriptomics datasets to define the comparable and distinct pathways that influence T cell function and behaviour within the different brain tumours. This will include focussing on the nature of communication between myeloid cells, stromal cells and neoplastic cells with T cell populations within the tumour microenvironment. Collectively, these analyses will prioritise treatment approaches to reinvigorate T cell responses during NF2-SWN tumours, which will be trialled within pre-clinical in vivo models.
Training/techniques to be provided:
The successful candidate will receive training in various cutting edge immunological techniques including imaging mass cytometry, flow cytometry, spectral flow cytometry, confocal and immunofluorescence microscopy, all combined with in vivo training. Associated with this work will be the development of excellent in vivo skills as well as in vitro use of cellular activation assays.
The student will become proficient in quantitative analyses of high-dimensional images, which will require developing expertise in statistics and computation. The student will utilise a number of existing RNA-seq libraries in their studies, providing experience and trainingin bioinformatics.
Thus, the successful candidate will obtain essential interdisciplinary and quantitative in vivo skills to support their future career. The student will be embedded within the wider neuroimmunology groups at the University and within the Geoffrey Jefferson Brain Research Centre, which will provide the student with outstanding further opportunities to increase their wider knowledge of immuno-oncology to develop their project through expert collaborations.
Entry requirements
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in Biology, Immunology or a related subject.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Immunology.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/programmes/integrated-teaching/
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.
If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
Funding Notes
References
Haley, M. J., Bere, L., Minshull, J., Georgaka, S., Garcia Martin, N., Howell, G., Coope, D., Roncaroli, F., King, A., Wedge, D. C., Allan, S. M., Pathmanaban, O. N., Brough, D. & Couper, K. N., 1 Apr 2024, (Accepted/In press) In: Science Advances.
Increased Circulating Chemokines and Macrophage Recruitment in Growing Vestibular Schwannomas
Hannan, C. J., Lewis, D., O'Leary, C., Waqar, M., Brough, D., Couper, K. N., Dyer, D. P., Vail, A., Heal, C., Macarthur, J., Cooper, C., Hammerbeck-Ward, C., Evans, D. G., Rutherford, S. A., Lloyd, S. K., Mackenzie Freeman, S. R., Coope, D. J., King, A. T. & Pathmanaban, O. N., 1 Mar 2023, In: Neurosurgery. 92, 3, p. 581-589 9 p.
The clinical, genetic, and immune landscape of meningioma in patients with NF2-schwannomatosis
Gregory, G. E., Islim, A. I., Hannan, C. J., Jones, A. P., Hammerbeck-Ward, C., Rutherford, S. A., Freeman, S. R., Lloyd, S., Kalamarides, M., Smith, M. J., Couper, K., McBain, C. A., Jenkinson, M. D., Brough, D., King, A. T., Evans, D. G. & Pathmanaban, O. N., 3 Jun 2023, In: Neuro-Oncology Advances. 5, Suppl 1, p. i94-i104
The comparable tumour microenvironment in sporadic and NF2-related schwannomatosis vestibular schwannoma
Gregory, G. E., Jones, A. P., Haley, M. J., Hoyle, C., Zeef, L. A. H., Lin, I-H., Coope, D. J., King, A. T., Evans, D. G., Paszek, P., Couper, K. N., Brough, D. & Pathmanaban, O. N., 21 Jul 2023, In: Brain Communications. 5, 4, fcad197.
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