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In my PhD thesis I am investigating the effect of a heart attack on the genome. A heart attack happens when a vessel of the heart is blocked and this leads to tissue ischemia. The restoration of the blood flow (reperfusion) is necessary to prevent the heart muscle from dying. But even if the blocked vessel was re-opened in time, patients suffer from long term consequences of this so called ischemia-reperfusion-injury.
My choreography shows the heart performing its pumping action and suddenly experiencing an ischemic event with the subsequent reperfusion. Activated immune factors come along with the restored blood stream. Upon this shock cardiac cells seem to change their character by activating some genes while deactivating others. This happens via so called epigenetic mechanisms.
Since our DNA is very long (approx. 2 meters per cell!) and the cells’ nucleus is very small (approx. 6 µm) the DNA needs to be packed. So, it is wrapped around histones, looking like pearls on a string. Histones have tails that can be chemically modified; depicted in the video by the “balloon hats”. The attached modifications determine whether the DNA can be read by the transcription machinery (Pol II), e.g. acetylation of these tails make DNA accessible. Activated by the ischemia-reperfusion event, enzymes quickly dance along the histones and modify their tails making some parts of the DNA accessible for transcription while inactivating others.
The dancers acting as the induced transcription factors show how the heart is threatened: they induce cell death and scar formation leading to the stiffness of the heart. The end of the performance shows a promising intervention strategy to treat ischemia-reperfusion-injury by fighting bad factors like Egr1 and reverse the induced histone modifications.
Part of Dance Your PhD 2014
