The Schnorrer group is welcoming applications for an ANR-funded PhD position to decipher molecular mechanisms how muscle nuclei sense mechanical pressure to adapt their transcriptional program.
PhD Project
Background:
Muscle cells assemble their contractile sarcomeres and their energy producing mitochondria during development. Their extreme packing produces high pressure on the muscle nuclei and squeezes these into elongated discs (left image). At the same time, these nuclei change transcription to allow sarcomere and mitochondria maturation. Here we would like to study how mechanical forces impact this transcriptional change. We have identified a novel BTB Zn-finger protein called Tono, which is acutely mechanosensitive and forms large phase-separated droplets, only minutes after pressure application (right images). We know that Tono is required for the transcriptional change to occur.
Aims:
- Characterise the developmental flight muscle proteome and metabolome using mass spectrometry and metabolomics to feed a mitochondrial flux model.
- Characterise the contents of the Tono nuclear droplets and their contribution to transcriptional activation or repression with super resolution imaging.
- Quantify the mechanically induced transcriptional changes by applying acute mechanical manipulations followed by live imaging and deep sequencing.
Our group and our environment
This interdisciplinary project will be hosted in a team of biologists, physicists and bioinformaticians, who are experts in muscle biology at the Developmental Biology Institute of Marseille (IBDM). You will collaborate with international experts in mass-spectrometry and metabolomics and travel to their labs. You will benefit from various state-of-the-art instrumentations and facilities at IBDM, including various high-end microscopes allowing live imaging and super resolution imaging.
Our group is part of the Turing Centre of Living Systems, Centuri, which brings together biologists, physicists, and computational scientists. Thus, you will benefit from an interdisciplinary environment, including collaborations, courses, seminars and meetings.
Your profile
You are a biologist, physicist or chemist with a core interest in quantitative biology. You are ambitious, enjoy to learn novel techniques and like to find answers to ambitious problems.
Contact
- Frank Schnorrer, andrea.pasini@univ-amu.fr
- Luis Nuno, nuno.luis@univ-amu.fr
- Schnorrer team, Muscle dynamics