DIsassembly-based Actin NEtwork contractility – Diane

Contraction of actin filament networks is a fundamental process for cells, and is widely conserved among eukaryotes. In addition to the well-known implication of the actin cytoskeleton for the contraction of muscle cells, contractile behaviors are also essential for many aspects of division and motility in non-muscle cells. Many defects related to the contraction of actin networks cause pathologies such as myopathies and cancers in mammals.
For many years, molecular motors were thought to be essential components for all actin-based contractile behaviors, and other possible mechanisms remained unexplored. However, recent evidences have emerged from theoretical and cellular studies, indicating the existence of an alternative mechanism based on a tight coupling of actin filament severing with active crosslinking. The objective of this project is to verify this model in vitro, by determining experimentally the conditions that are required to obtain efficient disassembly-based actin network contraction.
We will use an integrated approach with experiments ranging from the molecular to the cellular level. Our model system will be the yeast S. cerevisiae. At the molecular level, we will use a bottom-up approach from purified yeast proteins, to find the conditions in which crosslinkers and severing proteins reorganize and contract bulk mixtures of actin filaments or geometrically organized actin networks. We will combine these experiments with numerical simulations, and we will eventually validate our models of disassembly-based actin contraction in cells, by generating appropriate yeast mutants.
We expect that knowledge gained from these studies will provide a global vision of cell contractility, and a strong molecular basis for the future understanding of associated pathologies.