UKHSA project: Investigating the efficacy of ultra-high dose rates of ionizing radiation (FLASH radiotherapy) in reducing radiation toxicity during radiotherapy
Supervisors:
Lourdes Cruz-Garcia, Christophe Badie, Grainne O'Brien (UKHSA)
Mark Hill (Department of Oncology)
Project Overview:
Radiotherapy has been an effective tool for treating cancer alone or in combination with chemotherapy for more than 100 years. However, radiotherapy has side effects because it not only kills cancer cells but can also affect nearby healthy cells. The adverse effects of radiotherapy producing acute toxicities at short and long-term in healthy tissues severely affect the quality of life of surviving patients.
An emerging treatment plan, named FLASH radiotherapy (FLASH-RT), consists of delivering a single high dose of ionising radiation at very high-dose rates to the tumour (≥40Gy/sec compared to classic 1Gy/min). FLASH-RT has been shown to reduce considerably radiation-induced toxicity in surrounding radiation exposed healthy tissues without compromising the anti-cancer effects. Although this represents a potential ‘game changer’ in radiotherapy, the radiobiological mechanisms responsible for these sparing effects are not yet known.
This PhD proposal aims to study the DNA damage and inflammatory response of human healthy tissues (skin and blood) in response of ultra-high dose rates to understand the mechanisms involved in the FLASH effect. We will use proton and electron irradiations to achieve doses delivered at ≥ 40Gy/sec. Transcriptomic and proteomic analysis will be performed to identify genes and pathways modified by dose-rates. This research will provide an improved understanding on the molecular/cellular mechanisms associated with this emerging radiotherapy dose delivery technique. This is urgently required to assess and decide on the optimum way of implementing FLASH in clinical practice, to guide clinicians on the safe delivery of high doses of radiation and improve radiotherapy outcomes.
The student will be based in the UKHSA labs in Harwell Campus, Oxford. This is a funded DPhil project including fees, stipend and consumables funding. Please note, the studentship only covers fees at the UK Home rate.
Training Opportunities:
We will provide training in molecular biology techniques (RNA extraction, PCR, qPCR) together with cell culture, Elisa, western blot, nanopore library preparation, sequencing using a GridION/P2S sequencer and bioinformatic analysis.
Relevant Publications:
Matuszak, N., Suchorska, W.M., Milecki, P., Kruszyna-Mochalska, M., Misiarz, A., Pracz, J. and Malicki, J., 2022. FLASH radiotherapy: an emerging approach in radiation therapy. reports of Practical Oncology and radiotherapy, 27(2), pp.343-351. https://pmc.ncbi.nlm.nih.gov/articles/PMC9591027/
Cruz-Garcia, L., O'Brien, G., Sipos, B., Mayes, S., Love, M.I., Turner, D.J. and Badie, C., 2020. Generation of a transcriptional radiation exposure signature in human blood using long-read nanopore sequencing. Radiation research, 193(2), pp.143-154. https://pmc.ncbi.nlm.nih.gov/articles/PMC7055010/
Durante, M., Bräuer-Krisch, E. and Hill, M., 2018. Faster and safer? FLASH ultra-high dose rate in radiotherapy. The British journal of radiology, 91(1082), p.20170628. https://pmc.ncbi.nlm.nih.gov/articles/PMC5965780/