I am currently a postdoc in Sebastian Bonhoeffer's group at ETH Zurich, working mainly on stress-response, evolvability and robustness in bacteria.
Before this I was a PhD student with François Taddei and Dusan Misevic, at INSERM U1001 (Paris, France). My PhD focused on the links between second order selection and evolution of cooperation, using both microbial and in silico systems.
antoine DOT frenoy AT env DOT ethz DOT ch
gpg key: 0x3348CD09
Increased evolvability under stress: stress-induced mutagenesis and death
Stress-induced mutagenesis (SIM) has been a major paradigm shift in the past decades: it postulates that as an answer to stress, bacteria would increase their genome-wide mutation rate, for example thanks to over-expression of error-prone DNA polymerases, increasing the chances that a descendant is able to face the stress. This has implications for antibiotic treatment: a sub-inhibitory dose of antibiotics has been reported to increase the genome-wide mutation rate, and thus the rate at which resistance mutations appear, increasing the probability of treatment failure.
However currents methods do not allow to estimate mutation rate under a stress that affects population growth. Even a sub-inhibitory dose of antibiotics (or other stress) may trigger a significant death rate, although the population is still growing because division rate is still higher than death rate. We show that death will strongly bias mutation rate estimates, because death events will be compensated by more replications to reach a given population size (usually stationary phase), giving more opportunities to acquire mutations. Not taking into account these extra replications will lead to overestimating mutation rates in stressed populations.
Evolution of cooperation and second-order selection pressures
A part of my PhD relied on in silico simulations of bacterial evolution. To simulate the evolution and maintenance of cooperation in spatially structured environments, we use the Aevol system. Aevol is an individual-based model that has a bacterial-inspired genomic layer and is well suited to study second order selection pressures on genome structures. Aevol individuals have the ability to cooperate with each others by secreteting a diffusible public good molecule, costly to produce but beneficial to other individuals. We investigate the link between genome architecture and robustness of cooperation, going further than “classical” simulations of cooperation that often only consider two distinct behaviours. In Aevol there is a multitude of possibility of encoding a continuous secretion value, and all these possibilities have different robustness and evolvabilities, sometimes changing the fate of cooperation.
Genome architecture and the evolution of cooperation
Because genes coding for cooperation (here public good secretion) face very different selection pressures than more classical genes coding for private traits (affecting only the individual bearing them), we wondered whether they would somehow evolve different genetic properties.
We found that genes related to cooperation (coding for secretion of a public good) tend to spontaneously form operons (using the same promoters and terminators) and overlap (using the same base pairs but in different reading frames) with “metabolic” (only contributing to the focal individual's private fitness in our vocabulary) genes. A large part of “cheating” (decreasing secretion) mutations are thus also impacting “private” genes, causing a drop in fitness and the mutation being wiped out by selection [Frénoy et al, 2013, PLoS Computational Biology].
This shows the need of going beyond simple binary models when studying cooperation. Several recent studies show the potential relevance of this kind of second order selection pressures on cooperation in microbial world [Foster et al, 2004, Nature and Dandekar et al, 2012, Science].
We are currently applying this idea of evolvability suppresion by gene overlap to synthetic microbial systems. We designed algorithms allowing us to re-encode a gene, making him overlap with an other gene, and we are currently conducting mutagenesis experiments to show that this kind of evolutionary constraint can partially protect a costly gene from removal by mutations.
January 2015 - Now: Postdoc at ETH Zürich (Switzerland) with Sebastian Bonhoeffer.
September 2011 - November 2014: PhD in National Institute of Health and Medical Research (INSERM, Paris) with François Taddei and Dusan Misevic: “Second-order selection pressures promoting the evolution and maintenance of cooperation in microbial and in silico systems”
May - July 2011: Research internship in National Museum of Natural History (MNHN, Paris) supervised by Dominique Lestel and Hollis Taylor: “Evolution of music and language: bi-constructivist approach”
February 2010 - April 2011: Research internships and Master thesis in National Institute of Health and Medical Research (INSERM, Paris), supervised by François Taddei, Dusan Misevic and Julien Bénard-Capelle: “Using digital and microbial tools to investigate the evolution of cooperation in biological world”
May - July 2009: Research internship in Telethon Institute of Genetics and Medicine (TIGEM, Naples, Italy), supervised by Diego di Bernardo: “Network enrichment analysis: a new tool to understand complex biological networks”
June - July 2008: Research internship in National Institute for Research in Computer Science and Control (INRIA, Grenoble), supervised by Hidde de Jong (team Ibis): “Analysis of gene expression measurements: using reporter genes”
2011 - 2014: Frontiers in Life Science PhD program (FDV, Université Paris Descartes)
2010 - 2011: Interdisciplinary approaches to life science master program (AIV, Université Paris Diderot)
2009 - 2010: Parisian Master of Research in Computer Science (MPRI, École Normale Supérieure de Cachan)
2007 - 2009: B.Sc and Master 1 in theoretical computer science (École Normale Supérieure de Lyon)
2005 - 2007: Preparatory classes for entrance to the Grandes Écoles: Mathematics and physics (Lycée Thiers, Marseille)
September 2011 - 2014: Introduction to Matlab, in first year of AIV master program (Université Paris Descartes)
Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies (2017). B. Tepekule, H. Uecker, I. Derungs, A. Frénoy, S. Bonhoeffer.PLoS Computational Biology (html or pdf).
Second-order cooperation: Cooperative offspring as a living public good arising from second-order selection on non-cooperative individuals (2017). A. Frénoy, F. Taddei, D. Misevic.Evolution (html or pdf).
Discovery and function of a general core hormetic stress response in E. coli induced by sublethal concentrations of antibiotics (2016). A. Mathieu, S. Fleurier, A. Frénoy, J. Dairou, M.-F. Bredeche, P. Sanchez-Vizuete, X. Song, I. Matic.Cell Reports (html or pdf).
Shape matters: Lifecycle of cooperative patches promotes cooperation in bulky populations (2015). D. Misevic, A. Frénoy, A.B. Lindner, F. Taddei.Evolution (html or pdf).
Second order selection pressures promoting the evolution and maintenance of cooperation in microbial and in silico systems (2014), PhD thesis(pdf).
Genetic architecture promotes the evolution and maintenance of cooperation (2013). A. Frénoy, F. Taddei, D. Misevic.PLoS Computational Biology (html or pdf).
In silico evolution of transferable genetic elements (2013). D. Misevic, A. Frénoy, F. Taddei.In ECAL 2013: Proceedings of the twelfth European Conference on the Synthesis and Simulation of Living Systems (pdf).
Effects of public good properties on the evolution of cooperation (2012). D. Misevic, A. Frénoy, D.P. Parsons, F. Taddei.In Artificial Life XIII: Proceedings of the Thirteenth International Conference on the Simulation and Synthesis of Living Systems (pdf).
Robustness and evolvability of cooperation (2012). A. Frénoy, F. Taddei, D. Misevic.In Artificial Life XIII: Proceedings of the Thirteenth International Conference on the Simulation and Synthesis of Living Systems (pdf).