Mechanotransmission, Mechanotransduction and Lamina
Project acronym: MECALAM
Topics: cellular senescence, laminopathies, genetic mutations, nuclear envelope (NE)
Disciplinary fields: genetics, rare diseases, development biology, materials, nanosciences, nanotechnologies
Summary: Cellular senescence is the progressive decline of all cellular functions. When senescence is accelerated, it induces premature aging of patients and pathologies such as diabetes or cardiovascular diseases. Studies of rare premature aging syndromes like Progeria have identified a pathway to senescence related to a defect in lamin A, an important constituent of the nuclear lamina, itself being part of the nuclear envelope (NE). In this project, the first aim is to shed light on the relationship between altered mechanical properties of nuclei and cellular senescence. The means used are: the reproduction of premature senescence in model cell lines modified to express mutants of the NE constituents identified in severe laminopathies, or in cells treated by drugs that induce accelerated senescence. By coupling the results with physical analysis a progress will be made towards fast and cheap nucleus mechanics-based tests that could assess in further studies effects of anti-aging drugs and premature senescence tendency. A focus will be also made on the mechanotransductional response of cells when their NE is altered by the same mutations.
Project Interlocutor: Catherine Badens, Département de génétique médicale (UMR-S 910)
Project duration: 04/01/2018 – 03/31/2021
Call for application: Interdisciplinarité 2016