Grant: Team Grant: 4D Nucleome Transformative Collaborative Project

This project is dedicated to understanding of how genes are regulated in the cell's nucleus. We will investigate not only spatial parameters of such regulation but also temporal ones: how molecules surrounding DNA change during the 24 hour period (circadian cycle) as well as over months and years in the aging cells. This interdisciplinary research project combines three loosely associated fields - chromatin architecture, circadian biology, and aging. To the best of our knowledge, this is the first study exploring aging- related changes in chromatin architecture from the circadian perspective. Our intuitive and testable hypothesis may help to prove that ageing is, at least to some extent, deterministic. We will generate the first circadian map of interaction of regulatory elements, which will help understanding the 4D regulation of gene expression and other functional aspects of the nucleome. Our effort may show that spatial aspects of nuclear organization are inseparable from the temporal dimension, and that 'spacetime' is a critically important concept not only in physics but also in life sciences. This basic molecular biology study may have innovative translational implications. Establishing a relationship between aging and circadian rhythmicity may allow us to leverage circadian pathways to delay or reverse aging and aging- related diseases, such as cancer, type 2 diabetes, and Alzheimer's disease.