Accurate genome duplication and faithful transmission of genetic information are fundamental for cellular homeostasis and organismal survival. These processes rely on DNA replication and DNA damage repair, which in cells manifest as dynamic foci or compartment-like mesoscale structures. Over the past decades, many of the molecular factors involved have been identified, their functions characterized, and their interactions mapped with high structural resolution. Yet, key questions remain: How do these factors self-organize into mesoscale structures? What emergent biophysical properties arise from this organization? And how do these properties enhance the accuracy, efficiency, and regulation of DNA replication and repair?
Our laboratory addresses these questions with an interdisciplinary strategy. We reconstitute and purify key components of DNA replication and repair, and analyze them individually and in combination using quantitative biochemical and biophysical assays. These mechanistic studies are complemented by cell-based functional assays and, where possible, extended to disease models. Through this integrated approach, we aim to uncover the mechanisms that govern how replication and repair factors assemble into functional sites, establish selective compartments with distinct biochemical environments, confine and regulate enzymatic activities, and ensure the efficient transfer of substrates between factors. By uncovering these mechanisms, we aim to connect molecular processes with mesoscale organization and reveal how genome stability is safeguarded in human cells.
I am currently hiring a Technical Assistant. Learn more and apply through the job posting here.
In addition, I am actively recruiting for PhD and Postdoc positions.
PhD applicants: Find more information and apply via the IMPRS PhD program here.
Postdoctoral applicants: Please send an email to chappidi(at)mpi-cbg.de.