Description of the thesis topic

The Schnorrer and Michelot teams are seeking a candidate for a CNRS-funded international PhD position to understand how the evolution of actin isoform expression during muscle development drives the assembly and maturation of Drosophila sarcomeres. Scientific background: Muscle cells initially contain highly dynamic actin filaments, then assemble stable contractile sarcomeres at a defined stage of development. Each sarcomere contains ordered actin filaments and is mechanically linked to neighboring sarcomeres to form long, periodic chains. The peptide sequence of the muscle actin isoforms present in the sarcomeres is very similar to that of the non-muscle actin isoforms present in the initial dynamic filaments. Yet these two actin isoforms have different biochemical properties. In this project, we want to investigate why molecular differences between actin isoforms lead to a radical change in actin organization and dynamics in muscle cells. We aim to combine Drosophila genetics and in vivo imaging with actin biochemistry and in vitro actin imaging to understand how the molecular choreography of components leads to the assembly of sarcomeres in muscles. Aims: 1. characterize functional differences between Drosophila muscular and non-muscular actin isoforms by performing CRISPR knock-in permutations of their coding regions and analyze the resulting muscle phenotypes by confocal microscopy. 2. Manipulate the temporal dynamics of selected actin regulators to test their actin isoform specificity during sarcomere assembly in vivo. 3. Characterize in vitro, using single filament polymerization and TIRF microscopy, the biochemical properties of different actin isoforms and their interactions with selected actin-binding proteins. Your profile: You are a biologist, biochemist, physicist, chemist or engineer with a keen interest in quantitative biology. You're ambitious, curious, enjoy learning new techniques and finding answers to problems. You want to take advantage of the opportunity to do your PhD in two different countries and learn from different cultures and expertise.

Work Context

Located on the Luminy campus, IBDM employs around 220 permanent researchers, lecturers, engineers and technicians, as well as non-permanent staff on fixed-term contracts, post-docs, PhD students and trainees, spread across 21 research teams and 11 technical platforms and services. IBDM is a joint research unit under the supervision of CNRS and AMU, exploring the field of developmental biology and associated pathologies. The activity will be carried out within the “Muscular Dynamics” team, headed by Franck SCHNORRER. As the laboratory is made up of several nationalities, English is essential. This interdisciplinary project is an international collaboration between two groups based in Marseille and Singapore. You will be based in France in Frank Schnorrer's group at the Institut de Biologie du Développement de Marseille (IBDM). The Schnorrer team is expert in muscle biology and in vivo imaging. Objectives 1 and 2 will be carried out in Marseille. The group is part of the Turing Centre of Living Systems (Centuri), which brings together biologists, physicists and computer scientists. Your second base will be Alphée Michelot's group at the Mechanobiology Institute of Singapore (MBI) to achieve objective 3. The Michelot group is an expert in actin biochemistry and in vitro imaging. MBI is a leading multidisciplinary institute dedicated to developing new paradigms for understanding biological functions in health and disease from the perspective of cell, tissue and organ mechanics/dynamics and mechanical signal transduction.
The institute operates according to a fully integrated open laboratory philosophy, with an extensive infrastructure supported by core facilities dedicated to technologies such as advanced optical microscopy, nanofabrication and microfabrication, and informatics. This interdisciplinary project is an international collaboration between two groups based in Marseille and Singapore. You will be based in France in Frank Schnorrer's group at the Institut de Biologie du Développement de Marseille (IBDM). The Schnorrer team is expert in muscle biology and in vivo imaging. Objectives 1 and 2 will be carried out in Marseille. The group is part of the Turing Centre of Living Systems (Centuri), which brings together biologists, physicists and computer scientists. Your second base will be Alphée Michelot's group at the Mechanobiology Institute of Singapore (MBI) to achieve objective 3. The Michelot group is an expert in actin biochemistry and in vitro imaging. MBI is a leading multidisciplinary institute dedicated to developing new paradigms for understanding biological functions in health and disease from the perspective of cell, tissue and organ mechanics/dynamics and mechanical signal transduction. The institute operates according to a fully integrated open laboratory philosophy, with an extensive infrastructure supported by core facilities dedicated to technologies such as advanced optical microscopy, nano- and microfabrication, and informatics. Please send: Your CV.

Constraints and risks

You'll be working with bacterial cell cultures, Drosophila, chemicals, immunohistochemistry and microscopes. You'll also be working a lot in front of computers.