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Reference : UMR8237-ANDEST-007
Workplace : PARIS 05
Date of publication : Friday, August 27, 2021
Type of Contract : FTC Scientist
Contract Period : 18 months
Expected date of employment : 1 December 2021
Proportion of work : Full time
Remuneration : 32-47 k€ according to the candidate experience
Desired level of education : PhD
Experience required : Indifferent
The objective of the project is to design and implement synthetic materials that mimic the self-organizations observed during the development of an embryo. The aim will thus be to couple the two types of molecular self-organization mechanisms used in the laboratory, namely reaction-diffusion and active matter. The molecular systems used will be based on DNA and enzymes for the first one, microtubules and molecular motors for the second one.
By coupling these biochemical and mechanical self-organizations, we will seek to develop chemo-mechanical and mechano-chemical transductions within a "material". These active solutions will eventually be compartmentalized in communicating droplets, or integrated in a host material, a hydrogel for instance. We will thus move towards original synthetic materials, capable of spatialization, self-organization, growth or deformation.
Design and implement experiments (preparation of biochemical solutions, real-time PCR, fluorescence microscopy)
Exploit the results (data analysis, image processing)
Contribute to the scientific output (writing articles and conference presentations).
This is an experimental project combining DNA molecular programming and microtubule/kinesin active matter. Expertise in one of the two fields is required. Skills in expression and purification of recombinant proteins would be appreciated.
Rigor, autonomy, reliability.
Advanced level of oral and written English.
Located at the Laboratoire Jean Perrin, on the Pierre et Marie Curie campus of Sorbonne University (Paris 05), our group is interested in the molecular mechanisms responsible for the generation of order in living systems. Our objective is to better understand the rules that drive the emergence of this molecular order and to use this understanding to develop innovative materials inspired by life.
To do so we follow a "bottom up" approach which consists in developing dissipative molecular mechanisms capable of self-organization, in particular :
- a reaction-diffusion mechanism based on DNA and enzymes, which generate spatio-temporal concentration patterns, for example chemical fronts (Zadorin et al, Phys Rev Lett, 2015), or band patterns (Zadorin et al, Nature Chemistry, 2017).
- a microtubule and molecular motor-based active matter mechanism able to generate mechanical forces (Senoussi et al, PNAS, 2019 and Senoussi et al, bioRxiv, 2021).
This contract is part of the ERC project "Metabolic soft matter with life-like properties".
Constraints and risks
Risks associated with the handling of DNA intercalants, potentially carcinogenic, and the handling of potentially harmful chemical substances (solvents, etc.).
This position is asssociated to the ERC consolidator project "Metabolic soft matter with life-like properties" whose objectives are:
A fundamental difference between man-made and living matter is metabolism: the ability to dissipate chemical energy to drive many different chemical processes out of equilibrium. Metabolism endows chemical systems within living organisms with properties that are standard in biology but odd in chemistry: the capability to process information, to move and to react to the external world.
My goal is to endow soft materials with dynamic life-like properties. I have chosen four: molecular computation, movement, self-construction and the capacity to entertain complex chemical conversations with living cells. To do so I will embed stimuli-responsive materials with a biocompatible synthetic metabolism capable of sustaining autonomous chemical feedback loops that process information and perform autonomous macroscopic actions. My approach combines concepts from systems chemistry, synthetic biology and DNA molecular programming with soft materials and uses a biochemical system that I have contributed to pioneer: DNA/enzyme active solutions that remain out of equilibrium by consuming a chemical fuel with non-trivial reaction kinetics. This system has three unique properties: programmability, biocompatibility and a long-term metabolic autonomy.
Metabolic matter will be assembled in two stages: i) enabling metabolic materials with dynamic chemical, biological and mechanical responses, and ii) creating metabolic materials with unprecedented properties, in particular, the capacity of self-construction, which I will seek by emulating embryogenesis, and the ability to autonomously pattern a community of living cells. By doing this I will create for the first time chemical matter that is both dynamically and structurally complex, thus bringing into the realm of synthetic chemistry behaviors that so far only existed in biological systems. In the long term, metabolic matter could provide revolutionary solutions for soft robotics and tissue engineering.
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