The current geopolitical situation increases the need for knowledge and preparedness in the event of exposure to ionizing radiation from nuclear weapons or accidents. As of today, there is no treatment that can counteract the lethal effects of high radiation doses, only symptomatic treatment.
In our research, we have discovered that TGF-β3 (transforming growth factor beta 3) can influence the response of cells and animals to radiation and induce a protective effect when given before irradiation. Surprisingly, we found that it also worked when we administered TGF-β3 after irradiation. Mice that were exposed to a lethal radiation dose could be rescued by an injection of TGF-β3 24 hours after irradiation (78% survival compared to under 39%).
We have further investigated the mechanisms by which TGF-β3 modulates the radiation response and have found that this effect is mediated via a specific receptor (ALK1) and requires the presence of nitric oxide (NO) (and other factors). Our latest, unpublished data suggest that this protection depends on the Wnt signaling pathway and that it can be maintained over time through a positive feedback loop between NO and Wnt.
In this project we will aim to verify this mechanism and to identify downstream factors, primarily beta-catenin (canonical Wnt) and the survival protein survivin, which can directly prevent radiation-induced cell death.
TGF-β3 is a factor that can influence multiple processes in cells, and it has a complex interplay with TGF-β1. The goal of our research is therefore to identify target molecules and biological processes downstream of TGF-β3 that are more specific and suitable for therapeutic purposes.
This research is also relevant for the protection of astronauts in connection with space travel in the future.
The lab-work will involve cell irradiation and the measurement of different signals with molecular techniques such as flow cytometry, ELISA, or western blotting. To investigate the role of Wnt, NO and survivin, we will use selective inhibitors.
1. semester: 1. Learn the different experimental methods and do experiments.
2. semester: Last experiments, data analysis, and writing
We don't require any particular courses, but recommend FYS3700. FYS4720 and FYS4711 will give you all the theoretical background you need.