Investigation into the dynamics of DNA damage and repair of cells following FLASH and conventional irradiation
Primary Supervisor: Kristoffer Petersson PhD
FLASH radiation is a novel radiotherapy technique that shows great potential in improving cancer treatment.1 However, very little is known about the biological mechanisms behind the highly beneficial FLASH effect. Our research group aims to identify these mechanisms, explain the effect, and to find the optimal way of implementing the technique in clinical practice.
This project will focus on understanding not just the magnitude of DNA damage in cells following either FLASH or conventional irradiation but also the dynamics from induction to repair, and how it potentially varies between irradiation at ultra-high (FLASH, >100 Gy/s) and conventional dose rates (≈0.1 Gy/s). For this study, we will use our unique setup with a microscope in the experimental chamber of our FLASH dedicated linear accelerator and a robot capable of moving cell dishes from the point of irradiation to the microscope within a few seconds to allow monitoring of both early and late biological responses. We will explore the impact of FLASH on the DNA Damage Response through monitoring the kinetics of DNA damage induction and the repair of DNA double-strand breaks2 and other lesions 3 using physical (COMET assays), immunohistochemical (53BP1 and RAD51 foci formation) as well as genetic (siRNA and CRISPR deletions) approaches.
The student will be trained in various in vitro assays, such as comet assay, DDR analysis, and clonogenic assay. There will be opportunities to work with more advanced in vitro models, e.g. spheroids, organoids and 3D bio-printed tissue models. The student will also be trained in in vivo models. Correct dosimetry is essential in order to get useful and accurate preclinical results from our studies. Dosimetry also becomes more challenging at ultra-high dose rate. Hence, there will be some training opportunities in radiation dosimetry.
1. Wilson, J.D., Hammond, E.M., Higgins, G.S. and Petersson, K., 2020. Ultra-high dose rate (FLASH) radiotherapy: silver bullet or fool's gold?. Frontiers in oncology, 9, p.1563.
2. Adrian, G., Ruan, J.L., Paillas, S., Cooper, C.R. and Petersson, K., 2022. In vitro assays for investigating the FLASH effect. Expert Reviews in Molecular Medicine, 24.
3. Cooper, C.R., Jones, D., Jones, G.D. and Petersson, K., 2022. FLASH irradiation induces lower levels of DNA damage ex vivo, an effect modulated by oxygen tension, dose, and dose rate. The British Journal of Radiology, 95(1133), p.20211150.