Antoine Frénoy - Researcher in microbial evolution
I am an assistant professor in evolutionary biology and computer science at the University of Grenoble (France), working in the TIMC (biomedical engineering) department. I mostly focus on research questions around microbial evolution using quantitative methods. Most of my teaching is done at Ensimag, where I am in charge of the Mathematical modeling, computer graphics, and simulation specialization.
Until august 2019, I was a postdoc with Eduardo Rocha (Microbial Evolutionary Genomics) at Institut Pasteur, working on bacterial recombination in complex biotic environments using metagenomic and bioinformatic approaches.
Before this I was a postdoc with Sebastian Bonhoeffer (Theoretical Biology) at ETH Zurich, working mainly on stress-response, evolvability and robustness in bacteria (read our recent publication here).
And before I was a PhD student with François Taddei and Dusan Misevic (INSERM U1001). My PhD focused on the links between second order selection and evolution of cooperation, using both microbial and in silico systems (some of our work here and here).
Reach me : antoine DOT frenoy AT univ-grenoble-alpes.fr
Research
Bacterial recombination in complex biotic environments
During my postdoc with Eduardo Rocha, we used metagenomic datasets to extract quantitative properties of the biotic environment of bacterial species. The goal is to investigate how different lifestyles and biotic environments are linked with the use of recombination and horizontal transfer, as well as with the use of competition machineries (eg toxin or antibiotic production).
Increased evolvability under stress: stress-induced mutagenesis and death
Stress-induced mutagenesis has been a major paradigm shift in the past decades: it postulates that as an answer to stress, bacteria increase their genome-wide mutation rate. This has been interpreted as a mechanism providing “adaptation on demand” (increased evolvability under stress, increasing the chances that a descendant is able to face the stress).
In our series of two papers (Frenoy & Bonhoeffer, 2018, PLoS Biology and Vasse, Bonhoeffer and Frenoy, 2022, ISME communications), we challenge this view by showing that (1) current methods lead to a systematic over-estimation of mutation rate under bactericidal stress; and (2) a stress which increases mutation rate often does not increase evolvability because it also decreases population size, making mutation rate a poor predictor of evolvability.
To do so, we developped an experimental method to measure death rate in bacterial population using plasmid segregation, a computational method to estimate mutation rate when there is death, and a simple experimental measure of bacterial evolvability which encompasses mutation rate, population size, and population turnover.
Evolution of cooperation and second-order selection pressures
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.
To answer this question, we adapted the Aevol platform to the study of cooperation by implementing a spatial structure and the potential to secrete a public good. Aevol is an individual-based model that has a bacterial-inspired genomic layer and is has been used to study second-order selection pressures acting on genome organization.
We found (Frénoy et al, 2013, PLoS Computational Biology) 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.
We interpret this as an example of evolvability suppression (evolution of a trait constraining futur evolution). 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) and beyond (Altenberg, 2005, Artificial Life).
Current and past PhD students
Juliette Louistisserand (co-supervision, main advisor Magali Richard), since october 2024, on the link between tumor heterogeneity and eco-evolutionary processes in cancer
Quentin Fernandez de Grado, since december 2023, on the structure and evolutionary dynamics of bacterial genomes (using artificial life simulation methods)
Zakaria Tougui (co-advised with Nelle Varoquaux and Philippe Cinquin), since october 2023, on spatial study of the gut microbiome (using machine learning and uninvasive sampling methods)
Aurélien Tauzin, since october 2023, on parameter inference for bacterial population biology
Nagi Debbah (co-supervision, main advisor John Rendu (GIN)), from october 2021 to october 2024, on prediction of pathogenecity of genetic variants in a human gene (using structural modeling and machine learning)
Laura Turchi (co-supervision, main advisor François Parcy (LPCV)), from october 2020 to october 2023, on inference of regulatory sequences in plants
Publications
Beyond binding motif: genomic context predicts transcription factor dependent regulation in Arabidopsis (2025). L Turchi, J Lucas, G Tichtinsky, N Thierry-Mieg, R Blanc-Mathieu, F Parcy, A Frénoy*.bioRxiv preprint (html).
Ecological effects of stress drive bacterial evolvability under sub-inhibitory antibiotic treatments (2022). M Vasse, S Bonhoeffer, A Frénoy*.ISME Communications (html or pdf).
Engineering gene overlaps to sustain genetic constructs in vivo (2021). AL Decrulle*, A Frénoy*, TA Meiller-Legrand, A Bernheim, C Lotton, A Gutierrez, AB Lindner.PLoS Computational Biology (html).
The surprising creativity of digital evolution: A collection of anecdotes from the evolutionary computation and artificial life research communities (2020). J Lehman, J Clune, D Misevic, et al.Artificial Life (pdf).
Death and population dynamics affect mutation rate estimates and evolvability under stress in bacteria (2018). A Frénoy, S Bonhoeffer.PLoS Biology (html or pdf).
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, AB 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, DP 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).
I generally have research topics suitable for internships for licence and master students interested in computational or evolutionary biology. My research involves many computational, mathematical and statistical methods, but I am not interested in purely methodological topics.
These topics are also suitable for prospective PhD students in computational biology, but note that search for PhD should be anticipated as funding is scarse. In France the main source of PhD fundings are fellowships awarded to a student by the local university for a specific project in a specific lab (applications in spring for a start of PhD in october): it is important to reach potential labs way before the deadline to have the time to prepare the application together.
Others
Free E. coli and Salmonella knowledge: ecosalgenes.frenoy.eu, a modern online version of the list of genes that can be selected and counter-selected in these organisms, with links to Ecocyc and to full-text references. Useful for molecular cloning and microbial genetics, may become useful for system biology now that it is accessible in an easily parsable form!
Automatically remove these annoying watermarks that academic publishers insert in PDF: with this small python script, comments and suggestions welcome!