Akute Strahlenantwort

Damage responses and stress responses

Cellular damage after exposure to ionizing radiation is rapidly recognized, and restorative actions triggered. A damaged cell may be repaired without loss of integrity, may inadequately repair damage and be removed by surveillance mechanisms, or may survive without completely restoring the pre-irradiation state.
A cellular stress response accompanies the damage response, and is presumed to be due to the sustained free radicle production in irradiated cells. These two complimentary processes of damage and stress response influence the decision points for cell survival. Consequently they are key processes in the development of long-term health effects after irradiation such as cancer, vascular disease of the brain and heart, neurological impairment, or the formation of cataracts in the eye lens. The same processes are probably also key to the effective killing of tumour cells during radiation therapy, and offer an attractive target for therapy modulating drug interventions (Personalized Raditherapy)

Cellular responses to damage/ stress occur at the translational and transcriptional levels

Although DNA damage has been assumed to be the underlying cause of all radiation-induced diseases there are a number of inconsistencies in the logic, not least the lack of DNA damage and clonal expansion in non-cancer end points. In the search for alternative explanations the ISB research teams have demonstrated persistent alterations in the cellular proteome after irradiation that indicate pleiotropic damage to critical regulatory processes including mitochondrial function, cell motility and cytoskeletal function and intra- and inter cell signaling (Non Cancerogen Effects).

We have also shown that the non-coding transcriptome plays a key role in this early response, with both the microRNA and long non-coding RNA transcriptomes being critical to the response. Moreover, we have shown that low dose exposures, where only marginal health impacts are predicted, do not elicit the same biological responses as high doses where health detriments are clearly related to the received dose (Clinical Radiobiology)).

 Group strategy

The research group “Acute Radiation Response” has been formed to investigate the earliest cellular responses to ionizing radiation at the level of the transcriptome and proteome. We will use a systems biology approach to identify the critical regulatory pathways and to learn how their activation can lead to persistent effects on cell phenotype. At the same time we will search for critical nodes that can be effectively targeted to prevent cell survival during radiation therapy, in particular those where mutations provoke resistance to radiation therapy in fatal cancers.