PhD position available within the Turing Centre for Living Systems (CENTURI) program

http://centuri-livingsystems.org/phd2018-01/

http://centuri-livingsystems.org/phd2018-01/

Instructing myofibrillogenesis in human muscle by forces and shapes

Host laboratory and collaborators

Frank Schnorrer / IBDM / frank.schnorrer@univ-amu.fr

Olivier Theodoly / LAI / olivier.theodoly@inserm.fr

Presentation of the hosting teams

The Schnorrer lab pioneers the interface between developmental and cell biology with biophysics in order to understand how the ordered sarcomeric machine is assembled in Drosophila and human muscle models.

http://muscledynamics.org/

The Theodoly lab develops microfluidic and micropatterning tools to generate defined environments. These enable to quantitatively study the mechanical interaction of cells with their environment.

Scientific background

Skeletal muscle fibers are large multinucleated cells, which mechanically connect two skeletal elements.  The contractile forces are generated by highly regular mini-machines called sarcomeres, which are organized in long periodic chains called myofibrils. How can such long and regular myofibrils form during development? Using the fly model, the Schnorrer lab developed the tension-driven self-organization hypothesis of myofibrillogenesis, which suggests that mechanical tension acts as a compass to coordinate the assembly of many sarcomeres into long myofibrils. This hypothesis needs to be tested in human muscle.

PhD Objectives

We aim to generate human muscle fibers of defined sizes and shapes by 2D- or 3D-micropatterning and quantify the assembly and regularity of the sarcomeric pattern (Aim1). We then want to directly manipulate the forces by using stretchable PDMS-derived substrates and observe the impact on myofibrillogenesis (Aim2). Finally, we will directly quantify the forces generated by the differentiating muscle fibers by monitoring the deformation of the substrate with embedded beads (Aim3).

Proposed approach

In this inter-disciplinary PhD-project we take advantage of the extensive knowledge of the Theodoly lab in generation of micropatterned surfaces to directly quantify and manipulate forces and shapes of developing human muscle fibers in culture. We will use human induced pluripotent stem cells to generate a pure myoblast population that can be differentiated into millimeter long muscle fibers. This approach will directly test how defined forces and shapes instruct myofibrillogenesis in human muscle, and will thus generalize the tension-driven myofibril self-organization model to humans.

PhD student’s expected profile

The curiosity driven PhD student should have a firm biological or biophysical education and enjoy to work at the interface between biology and biophysics. Experience in quantitative imaging, image analysis or bioengineering is a plus.

 PhD position in the Schnorrer lab

Biomechanics of Sarcomeres

You:
You are a curiosity-driven young scientist, fascinated by nature;
You enjoy pursuing a challenging, highly innovative project;
You would like working with the Drosophila model;

We:
We are located at Institute of Developmental Biology of Marseille (IBDM), an interdisciplinary research center with a strong focus on quantitative in vivo biology and biophysics;
We study the morphogenesis of muscle with a particular interest in the contractile apparatus, sarcomeres and myofibrils;
We combine systematic fly genetics with in vivo imaging;
http://muscledynamics.org
http://www.ibdm.univ-mrs.fr/equipe/muscle-dynamics

Goal:
This project aims to manipulate the mechanical properties of sarcomeric components, in particular of the gigantic spring domain protein titin and observe the phenotypic consequences;
This will apply innovative CRISPR-based genome modification strategies and super-resolution imaging;

Please send your application, including a motivation letter, your CV, a description of research interests, and contact information for two references to:
frank.schnorrer@univ-amu.fr

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