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Reference : UMR8237-ANDEST-004
Workplace : PARIS 05
Date of publication : Thursday, May 21, 2020
Type of Contract : FTC Scientist
Contract Period : 12 months
Expected date of employment : 1 September 2020
Proportion of work : Full time
Remuneration : 3000 € brutto per month
Desired level of education : PhD
Experience required : 1 to 4 years
The objective of the project is to couple DNA-based molecular programs to living cells to make living materials with well-controlled dynamics. The question we ask ourselves is: can we make hybrid materials combining living and artificial elements and which mimic the self-organization implemented during the development of an embryo?
Thinking, cell culture, fluorescence microscopy, setting up complex experiments, writing articles. Presentations.
It is an experimental project combining biochemistry of nucleic acids and synthetic biology of eukaryotic cells. Biochemical kinetics, fluorescence microscopy and image analysis. It is also an interdisciplinary project, at the interface between physico-chemistry, biophysics, synthetic chemistry, cell biology, molecular programming based on DNA and millifluidics.
Our research group is interested in the molecular mechanisms responsible for the generation of order in living systems. We do this with two goals: to understand the emergence of the molecular order and use it to develop innovative materials inspired by life. To do this we study dissipative molecular programs that self-organize in space and time. These synthetic molecular programs are developed in the laboratory using a highly programmable biochemistry of nucleic acids and enzymes.
How is it that an organism made up of molecules of nanometric size organizes itself in a structure of millimetric size, as it is the case for an embryo? Can one draw inspiration from the development of the embryo to design artificial materials that are built themselves? In order to study these questions we use a bottom-up approach which consists in developing dissipative molecular programs reproducing two types of mechanisms responsible for the generation of order in the living. Reaction-diffusion mechanisms that generate spatial concentration structures, such as chemical waves (Zadorin et al., Phys Rev Lett, 2015), or band generators (Zadorin et al, Nature Chem, 2017). And mechanisms of active type that generate forces locally and therefore spatial structures of flows.
Constraints and risks
Risks associated with the handling of DNA intercalants, potentially carcinogenic, and the handling of potentially harmful chemical substances (solvents, etc.).
This contract belongs to the ERC 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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