Jobs
PhD Position | ACTIN-SHIFT: Molecular mechanisms by which actin isoforms control sarcomere assembly
PhD Project
Background:
Muscle cells initially contain very dynamic actin filaments and then assemble stable contractile sarcomeres at a defined stage during development. Each sarcomere contains highly ordered actin filaments and is mechanically connected to neighbouring sarcomeres forming long periodic chains (left image). The peptide sequence of muscle actin isoforms present in sarcomeres is highly similar to nonmuscle actin isoforms which are present in the early dynamic filaments. Yet these two actin isoforms have different biochemical properties. Here, we would like to study the mechanism by which molecular differences in actin isoforms lead to a dramatic shift 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 assembly imaging to understand how the molecular choreography of the components drives sarcomere assembly in muscles.
Aims:
- Characterise the functional differences between the Drosophila muscle and nonmuscle actin isoforms by performing CRISPR-based knock-in swaps of their coding regions and analyse the resulting muscle phenotypes by confocal microscopy.
- Manipulate the temporal dynamics of selected actin regulators to test their actin isoform specificity during sarcomere assembly in vivo.
- Characterise the biochemical properties of the different actin isoforms and their interactions with selected actin binding proteins in vitro using single filament polymerisation and TIRF microscopy (right image).
Our group and our environment
This interdisciplinary project is an international collaboration between two groups based in Marseille and in Singapore.
The homebase for you will be the group of Frank Schnorrer at the Developmental Biology Institute of Marseille (IBDM). The Schnorrer group is expert in muscle biology and in vivo imaging. Aims 1 and 2 will be performed in Marseille. The 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 in Marseille.
Your second base will be the group of Alphée Michelot at the Mechanobiology Institute in Singapore (MBI) to achieve Aim 3. The Michelot group is expert in actin biochemistry and in vitro imaging. The MBI is a leading multidisciplinary institute devoted to developing new paradigms for understanding biological functions in health and diseases from the perspective of cell, tissue and organ mechanics/dynamics and mechano-signal transduction. The institute operates on a fully integrated open-lab philosophy, with an extensive infrastructure supported by core facilities dedicated to technology such as state-of-the-art light microscopy, nano- and micro- fabrication, and computing.
Your profile
You are a biologist, biochemist, physicist, chemist or engineer with a core interest in quantitative biology. You are ambitious, curious, enjoy to learn novel techniques and like to find answers to problems. You want to take advantage of the opportunity to carry out your doctorate in two different countries and learn from different cultures and expertise.
Your application
Please apply here by October 7th 2024:
by uploading:
– Your CV.
– Your academic transcripts in a single document.
– A personal statement that includes your professional goals and your motivation for wanting to join our labs.
– A brief summary of your past internships (max. 200 words per internship).
– Contacts of two references.
Contact
- Frank Schnorrer, frank.schnorrer@univ-amu.fr
- Alphée Michelot, alphee.michelot@univ-amu.fr
- Schnorrer team, Muscle dynamics
References
1- Spletter et al. A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle. eLife 2018. doi: 10.7554/eLife.34058
2- Gressin et al. Architecture dependence of actin filament network disassembly. Curr Biol. 2015. doi: 10.1016/j.cub.2015.04.011.
3- Boiero-Sanders et al. Specialization of actin isoforms derived from the loss of key interactions with regulatory factors. EMBO J. 2022. doi: 10.15252/embj.2021107982
M2 MCT/BIP (RPE and porins)
PhD Project
Background:
Muscle cells initially contain very dynamic actin filaments and then assemble stable contractile sarcomeres at a defined stage during development. Each sarcomere contains highly ordered actin filaments and is mechanically connected to neighbouring sarcomeres forming long periodic chains (left image). The peptide sequence of muscle actin isoforms present in sarcomeres is highly similar to nonmuscle actin isoforms which are present in the early dynamic filaments. Yet these two actin isoforms have different biochemical properties. Here, we would like to study the mechanism by which molecular differences in actin isoforms lead to a dramatic shift 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 assembly imaging to understand how the molecular choreography of the components drives sarcomere assembly in muscles.
Aims:
- Characterise the functional differences between the Drosophila muscle and nonmuscle actin isoforms by performing CRISPR-based knock-in swaps of their coding regions and analyse the resulting muscle phenotypes by confocal microscopy.
- Manipulate the temporal dynamics of selected actin regulators to test their actin isoform specificity during sarcomere assembly in vivo.
- Characterise the biochemical properties of the different actin isoforms and their interactions with selected actin binding proteins in vitro using single filament polymerisation and TIRF microscopy (right image).
Our group and our environment
This interdisciplinary project is an international collaboration between two groups based in Marseille and in Singapore.
The homebase for you will be the group of Frank Schnorrer at the Developmental Biology Institute of Marseille (IBDM). The Schnorrer group is expert in muscle biology and in vivo imaging. Aims 1 and 2 will be performed in Marseille. The 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 in Marseille.
Your second base will be the group of Alphée Michelot at the Mechanobiology Institute in Singapore (MBI) to achieve Aim 3. The Michelot group is expert in actin biochemistry and in vitro imaging. The MBI is a leading multidisciplinary institute devoted to developing new paradigms for understanding biological functions in health and diseases from the perspective of cell, tissue and organ mechanics/dynamics and mechano-signal transduction. The institute operates on a fully integrated open-lab philosophy, with an extensive infrastructure supported by core facilities dedicated to technology such as state-of-the-art light microscopy, nano- and micro- fabrication, and computing.
Your profile
You are a biologist, biochemist, physicist, chemist or engineer with a core interest in quantitative biology. You are ambitious, curious, enjoy to learn novel techniques and like to find answers to problems. You want to take advantage of the opportunity to carry out your doctorate in two different countries and learn from different cultures and expertise.
Your application
Please apply here by October 7th 2024:
by uploading:
– Your CV.
– Your academic transcripts in a single document.
– A personal statement that includes your professional goals and your motivation for wanting to join our labs.
– A brief summary of your past internships (max. 200 words per internship).
– Contacts of two references.
Contact
- Frank Schnorrer, frank.schnorrer@univ-amu.fr
- Alphée Michelot, alphee.michelot@univ-amu.fr
- Schnorrer team, Muscle dynamics
References
1- Spletter et al. A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle. eLife 2018. doi: 10.7554/eLife.34058
2- Gressin et al. Architecture dependence of actin filament network disassembly. Curr Biol. 2015. doi: 10.1016/j.cub.2015.04.011.
3- Boiero-Sanders et al. Specialization of actin isoforms derived from the loss of key interactions with regulatory factors. EMBO J. 2022. doi: 10.15252/embj.2021107982
M2 SOLEIL (DUV microfluidics and SHG)
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