Chromatin Mobility in DNA damage repair and tumorigenesis: exploring the role of nuclear architecture

DNA integrity is essential to preserve the correct cellular identity and functions within an organism, and genome instability is linked to cancer onset/progression and degenerative diseases.

To recognize and repair DNA damage, eukaryotic cells have evolved a network of pathways, among which chromatin mobility is emerging as a key player. Yet its molecular details remain elusive.

Here, we will elucidate the interactions between DNA damage, chromatin mobility, nuclear envelope architecture and, ultimately, DNA repair.

In details, we will investigate how variations in the nuclear stiffness affect chromatin mobility, and how chromatin mobility impacts DNA repair, with a focus on deleterious genome rearrangements.

In parallel, we will identify DNA damage-dependent alterations in the nuclear envelope and the molecular mechanisms regulating them. The research team will comprise a project leader, two PhD students and one postdoc.

We will apply multiple approaches, from genetic to environmental to alter the nuclear stiffness; live-cell fluorescence microscopy to quantify chromatin mobility and nuclear membrane changes; and a combination of metaphase and sequencing analysis for chromosomal rearrangements detection.This study will reveal how differences in nuclear architecture affect genome stability under physiological and pathological conditions.

We anticipate that the project will help the development of specific diagnostic tools and targeted therapies for different types of cancer.