Anthony GENOT, Dr.

genot.jpg Host Laboratory FUJII LAB.
Position in LIMMS CNRS Researcher

Main Research Topic in LIMMS

Bio-MEMS - Molecular programing in micro-nano systems

Keywords

DNA nanotechnology, Droplet microfluidic, Nonlinear chemistry
Contact LIMMS/CNRS-IIS (UMI 2820)
Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
Phone:+81 (0)3 5452 6036 / Fax:+81 (0)3 5452 6088
E-mail genot at iis.u-tokyo.ac.jp
Download  icon_pdf.gifAbstract2015_AGenot.pdf , Abstract2016

Resume

Short resume :
2014-now CNRS Research Associate (CR2), LIMMS
2013-2014 ANR Retour Postdoc fellow, LAAS, CNRS, Toulouse, France
2011-2013 JSPS Postdoctoral fellow LIMMS
2006-2011 Phd student and postdoctoral fellow, Physics Department, University of Oxford, UK

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Research Projects in Limms

1- Molecular programing in micro-nano systems

Context :
Molecular programing is an emerging field whose goal is two-fold. First it aims to program molecules to process signals at the micro-nano scale in order to orchestrate complex mechanisms and engineer new functions. Secondly, it is expected that this learning-by-doing approach will shed light on the programing paradigm actually employed by biological organisms to sense, process and actuate information. DNA has emerged in the last 2 decades as a perfect material for molecular programing, allowing among other things the folding of arbitrary nanoscale shapes, the classification of chemical patterns or the smart delivery of drug payloads.
Objectives & Methods :
Our objective is to demonstrate innovative computational behaviors in micro-nano systems. We use DNA as a programmable polymer to encode the topology of a reaction network consisting of activation and inhibition interactions. We also use enzymes to continuously synthetize and destroy DNA according to the rules of the network in order to drive the system out-of-equilibrium, which enables new dynamic such as oscillations [1] and bistability [2]. In order to manipulate and monitor molecular program with high-throughput, we develop ad-hoc microfluidic tools such as droplet microfluidic, which allows a reduction of volume and preparation time by several orders of magnitudes.
Results :
We have recently demonstrated the first high-throughput mapping of a nonlinear biochemical system using droplet microfluidic. The large-scale of the data sets (10000 data points) has allowed us to discover subtle dynamic in a bistable circuit. In addition to delineating the bifurcation frontiers in the parameters space, we have highlighted experimentally how global competition for the processing enzymes shape the reactional landscape in surprising ways –confirming theoretical predictions made earlier [3,4]. 
Genot_Fig1.jpg
                          Fig. 1 Confocal microscopy image of an array of water-in-oil droplets containing a bistable circuit. Each droplet contains 4 fluorescent dyes, whose intensities encode for the input and output state.
References :
[1] K. Montagne, et al., MSB. 2011.
[2] A. Padirac, PNAS, 2012
[3] Y. Rondelez, PRL, 2011
[4] A.J. Genot et al., PRL, 2012

 

2- Mapping the phase diagram of an analog DNA circuit

Context :
DNA is not only the carrier of genetic information, but also a formidable polymer with which to build at the molecular scale. The predictability of DNA self-assembly has powered the construction of a rich library of nanoscale structures and devices: crystals, neural networks, walker or logic circuits.
Recently, Rondelez and colleagues in LIMMS have reported a powerful toolbox to go beyond the Boolean paradigm and reach into the little-explored field of nonlinear chemistry. By programming interactions between activating and inhibiting species, they demonstrated signature behaviors of nonlinear chemical systems: oscillations and multi-stability.
Yet thoroughly testing those analog circuits poses a tremendous challenge. For instance, varying 2 concentrations with 100 steps for each requires preparing no less than 10 000 solutions. This combinatorial explosion that accompanies complex circuits is well known from engineers in the electronic industry.
Results :
We have developed a microfluidic platform to combinatorially prepare thousands of DNA circuits in sub-nanoliter droplets, which represent an improvement of several orders of magnitudes over bulk and manual preparation. We have demonstrated the viability of the platform by monitoring hundreds of biochemical oscillators encapsulated in droplets [2].
We next applied this technology to precisely map the phase diagram of a bistable switch. The diagram (Figure 1) is based on analyzing ~10 000 droplets. While qualitatively similar to deterministic simulations, it hints a stochastic behaviours induced by the very small reaction volumes of the droplets.
Fig1_autocatalytic_Genot.jpg                                                                              Fig. 1 Phase diagram of a bistable switch in function of the concentration of autocatalytic templates injected.
References :
[1] Montagne, et al., Molecular Systems Biology 2011.
[2] Hasatani et al., Chemical Communications, 2013 

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Main publication List (papers, conferences and patent)

2014

Journals
Conferences

 

2013

Journals
  1. K. Hasatani, M. Leocmach, A. J. Genot, A. Estevez-Torres, T. Fujii, Y. Rondelez, High-throughput observation of compartmentalized biochemical oscillators, Chem. Commun., DOI:10.1039/C3CC44323J (2013).
  2. A Genot, T. Fujii & Y. Rondelez, Scaling down DNA circuits with competitive neural networks, J. R. Soc. Interface, 10, 20130212 (2013).
  3. A. Genot, T. Fujii & Y. Rondelez, In vitro regulatory models for systems biology. Journal of Biotechnology Advances, , http://dx.doi.org/10.1016/j.biotechadv.2013.04.008 (2013).
Conferences

 

2012 and prior

Journals
  1. A. Genot, T. Fujii & Y. Rondelez, Competition and computation in biomolecular networks. Phys. Rev. Let. 109 208102 (2012).
Conferences
  1. A.J. Genot, FNANO2012 Snowbird, USA 16-19.04.2012.

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