Is metabolic reprogramming the key to treatment failure in aggressive brain tumours? A multi-nuclear in vivo ultrahigh-field MRI approach.


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  Prof Dorothee Auer  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Glioblastoma is the deadliest brain cancer with poor survival rates despite improved understanding of its genetic causes; novel treatments in lymphomas offer survival benefits for some people with lymphomas, but when treatments fail, the median survival time is ~5 months. One reason for these poor treatment responses is the complex way in which cancer cells adapt their energy production, through a process called metabolic reprogramming. A lot of current research is therefore focused on producing a better understanding of metabolic reprogramming, so as to inform the development of effective treatments.

MRI is usually based on signals from hydrogen in water and fat, but it is also possible to make images based on signals from deuterium. As there is only a very small amount of naturally occurring deuterium in our bodies, after feeding someone with a compound containing deuterium the signal we detect mainly comes from ingested material. Measuring deuterium signals following ingestion of labelled glucose allows us to track metabolic processes involved in energy production in brain tissues. We have implemented this deuterium metabolic imaging (DMI) approach on our 7T scanner, and this PhD project will focus on applying DMI to understanding metabolic reprogramming in aggressive glioblastoma and lymphoma tumours.

 Preliminary studies have demonstrated the feasibility of DMI, and the successful candidate will expand on this work by refining the acquisition protocol for regular clinical use across a range of MRI platforms (3T, 7T and 11.7T). The candidate will also explore the use of novel RF coils, MR sequences and other deuterated labelling molecules. This multi-disciplinary project presents an exciting opportunity to combine cutting-edge brain tumour research, MR physics and dynamic spectral analysis. The student will be supported in all these aspects by supervisors based at the Nottingham Biomedical Research Centre, The Sir Peter Mansfield Imaging Centre and The Centre for Human Brain Health.

Biological Sciences (4) Medicine (26)

Funding Notes

This is a fully funded studentship provided by the Medical Research Council. If successful, you will receive a stipend (currently £18,622 per year for 2023/24) and tuition fee waiver for 4 years. Successful candidates will also receive an allowance for a laptop, a travel and conference allowance plus allowance for laboratory/PhD running costs.
Click on the institution website link which will redirect you to the MRC AIM website which contains full application information including application forms to complete. Please ensure you submit your application before the deadline of midday (GMT) Friday 12 January 2024 as late applications will not be considered.

References

(1) Louis DN, et al. Neuro Oncol. 2021 Aug 2;23(8):1231-1251
(2) Masui et al., Neuropathology 2019; 39: 3-13
(3) Ge et al., Can Comm 2022 Nov; 42 (11): 1049-1082
(4) Mishkovsky et al., Sci Rep 2021 Mar: 5771
(5) El Khayari et al., Front Oncol 2022 Jul; 901951
(6) Takashima et al. Clin Cancer Res (2020) 26 (11): 2754–2766.
(7) deFeyter et al., Sci Adv 2018 Aug; 4(8): eaat 7314
(8) Cocking et al, MRM 2022 Nov; 1-8.
(9) Cocking et al. ISMRM 2023 (Conference paper)

Where will I study?

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