Understanding DNA damage over tissue development and aging time-scales – ChronoDamage

Our proposed work aims to better understand how exogenous and physiological mechanical forces may be buffered, or promote DNA damage and how this impacts developing and adult tissues over short and long time-scales. We will combine interdisciplinary approaches from the teams of Partner 1 (Allison Bardin) and Partner 2 (Yohanns Bellaïche) including live-imaging of DNA damage, novel devices to induce mechanical tissue compression, genetic tools as well as tissue physiological assays. We will explore the checkpoint processes allowing detection of DNA damage upon tissue compression (Aim 1). We will then examine the extent to which DNA damage is induced by physiological tissue mechanical movements or is buffered (Aim 2). Finally, we will examine the short and long-term impact that mechanical forces have on genome integrity during aging, and conversely, how aging itself impacts the mechanical properties of the gut (Aim 3).