Fiche Projet - Ecole Doctorale Complexité du vivant

Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Nom et prénom du directeur de thèse (et si besoin du co-directeur) : Marie-Anne FELIX
Coordonnées
Tel :
01-44-32-39-44
e-mail : [email protected]
Nom et prénom du responsable de l’équipe : Marie-Anne FELIX
Nombre de chercheurs et enseignants-chercheurs statutaires de l’équipe titulaires d’une HDR : 0 (mais PR)
Nom et prénom du responsable du laboratoire : Antoine TRILLER
Intitulé du laboratoire et N° d’unité : Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, Inserm U1024
Spécialité : Génétique, Evolution.
Titre du projet de thèse :
Suppression of a multigenerational sterility phenotype in the nematode C. elegans
by ecologically relevant micro-organisms
Résumé du projet de thèse (1 page maximum, en anglais)
The germ line of multicellular organisms is a cellular lineage that is maintained indefinitely along
organismal generations. Lack of proper germ line maintenance results in lineage extinction. In the
nematode Caenorhabditis elegans, mutants that display a mortal germline phenotype (i.e. that become
sterile after several generations) have been isolated in the reference genetic background N2. The
mutations affect a diversity of processes, including DNA repair; a subclass is temperature-sensitive
and affects histone methylation and the synthesis of piRNAs and of 2° siRNAs in the germ line (e.g.
ref. 1-3).
By sampling isolates of C. elegans from the wild, we noticed that, surprisingly, many displayed
a temperature-sensitive mortal germline phenotype. Among those with a strong phenotype, each
displays a characteristic mean number of generations until sterility at a given temperature. For
example, the half-life in generations of the C. elegans wild isolate JU775 is of 4 generations at 25°C, 5
at 23°C, and 10 at 21.5°C, when cultured in standard laboratory conditions, feeding on E. coli OP50.
We are investigating the mechanistic basis for this sterility and for the variation among wild isolates.
We found that 2° siRNAs are depleted just before the onset of sterility (L. Frézal, E. Miska and M.-A.
F).
The present project is based on the additional recent serendipitous observation (G. Zhang and
M.-A. F.) that infection of C. elegans JU775 and JU2526 by microsporidia suppresses their mortal
germline phenotype. Microsporidia are obligate intracellular parasites that are closely related to fungi.
We discovered microsporidia species that infect Caenorhabditis in the wild, named Nematocida parisii
and Nematocida sp. 1, which are horizontally transmitted and infect the intestinal cells of C. elegans
(ref. 4).
The aim of the present project is to investigate the mechanism of suppression of the mortal
germline phenotype by micro-organisms such as microsporidia, and its ecological and evolutionary
significance, wiht two complementary approaches:
1. Characterize the range of micro-organisms that suppress the mortal germline
phenotype and the specificity of their interaction with the germline phenotype of different C.
elegans isolates. We will test various microsporidia, bacteria, fungi, and virus from our sampling
collections on a small set of C. elegans wild isolates showing a mortal germline phenotype. We will
test whether immunity to microsporidia may be transmitted across generations in different wild
isolates. In addition, we will characterize the relevant associated micro-organisms in wild-caught C.
elegans showing a mortal germline phenotype when the microorganisms are removed by treating the
culture with bleach (as was already observed by MAF).
2. Identify mechanisms of mortal germline suppression, including signaling between
soma and germline, through standard reverse and possibly forward and quantitative evolutionary
genetic approaches, and various molecular and cellular tools in C. elegans. The exact strategy will
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Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
depend on results from part 1 and the specificity and site of action. As a first step, we will characterize
the transcriptome and small RNA content upon infection during the course of the mortal germline
appearance in unsuppressed versus suppressed C. elegans lineages. An obvious candidate to be
explored is the insulin pathway (ref. 3).
In summary, this project addresses an exciting type of interaction between an animal and
associated micro-organisms. If the mortal germline phenotype of these wild isolates reflects a defect in
the multigenerational transmission of some small RNAs, its modulation by interacting micro-organisms
(at least some of which are conditionally pathogenic) will be of great evolutionary and ecological
signiificance.
1. Smelick, C. and Ahmed, S. 2005. Ageing Res Rev 4 (1):67-82.
2. Buckley, B. A, et al. 2012. Nature 489 (7416):447-51.
3. Simon, M et al.. 2014. Cell Reports 7, 762-773.
4. Troemel, E. et al. 200s8. PLoS Biol. 6, e309.
Thèses actuellement en cours dans l’équipe
Nom et Prénom du doctorant
ZHANG Gaotian
VARGAS VELAZQUEZ Amhed
Nom du directeur de thèse
Marie-Anne FELIX
Marie-Anne FELIX
Année de 1ere
inscription et
Ecole Doctorale
2013
2014
Financement pendant la thèse
ECNU Shanghai
Labex MemoLife
Trois publications récentes du directeur de thèse (du co-directeur ou du co-encadrant s’il y a lieu).Mettre en gras le nom
du directeur de thèse.
Barkoulas, M., van Zon, J.S., Milloz, J., van Oudenaarden, A., Félix, M.-A. (2013). Robustness and epistasis in the C.
elegans vulval signalling network revealed by pathway dosage modulation. Dev. Cell 24, 64-75.
Ashe, A.*, Bélicard, T.*, Le Pen, J.*, Sarkies, P.*, Frézal, L., Lehrbach, N.J., Félix, M.-A.#, Miska, E.A.# (2013). A deletion
polymorphism in the C. elegans RIG-I homolog disables viral RNA dicing and antiviral immunity. eLife 2:e00994. (*: cofirst authors; #: co-last authors)
Félix, M.-A. and Barkoulas, M. (2015). Pervasive robustness in biological systems. Nat. Rev. Genet. 16, 483-496.
Docteurs encadrés par le directeur de thèse ayant soutenu après septembre 2010 et publications relatives à leur sujet de thèse.
Mettre en gras le nom du directeur de thèse et celui du docteur.
Nom Prénom : PENIGAULT Jean-Baptiste
Date de soutenance : 2/12/2010
Durée de thèse (en mois): 50
Ecole Doctorale : B3MI, Université Paris Diderot
Publications :
Hoyos, E*, Kim, K*, Milloz, J, Barkoulas, M, Pénigault, J-B, Munro, E, Félix, M-A. Quantitative variation in
autocrine signaling and pathway crosstalk in the Caenorhabditis vulva network. Curr. Biol. 2011, 21, 527-538 (format
long).
Pénigault, J-B, Félix, M-A. High sensitivity of C. elegans vulval precursor cells to the dose of posterior Wnts. Dev.
Biol. 2011, 357:428-438.
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Ecole Doctorale COMPLEXITE DU VIVANT – Fiche Projet CONCOURS
Pénigault, J-B, Félix, M-A. Evolution of a system sensitive to stochastic noise: P3.p cell fate in Caenorhabditis. Dev.
Biol. 2011, 357:419-427.
Kiontke, K*, Félix, M-A*, Ailion, M, Rockman, MV, Braendle, C, Pénigault, J-B, Fitch, DHA. A phylogeny and
molecular barcodes for Caenorhabditis, with numerous new species from rotting fruits. BMC Evol. Biol. 2011, 11:339.
Nom Prénom : DUVEAU Fabien
Date de soutenance : 29/09/2011
Durée de thèse (en mois): 48
Ecole Doctorale : B3MI, Université Paris Diderot
Publications :
Milloz, J, Duveau, F, Nuez, I, Félix, M-A. Intraspecific evolution of the intercellular signaling network underlying a
robust developmental system. Genes Dev. 2008, 22:3064-307.
Duveau, F, Félix, M-A. Hidden variation mapped. Heredity 2010, 105:423-425.
Duveau, F, Félix, M-A. Role of pleiotropy in the evolution of a cryptic developmental variation in C. elegans. PLoS
Biol. 2012, 10: e1001230.
Félix, M-A., Duveau, F. Population dynamics and habitat sharing of natural populations of Caenorhabditis elegans
and C. briggsae. BMC Biol. 2012, 10:59.
Nom Prénom : BELICARD Tony
Date de soutenance : 18/09/2014
Durée de thèse (en mois): 48
Ecole Doctorale : Complexité du Vivant
Publications :
Félix MA*#, Ashe A.*, Piffaretti J*, Wu G, Nuez, Bélicard T, Jiang Y, Zhao G, Franz CJ, Goldstein LD, Sanroma,
M, Miska EA# and Wang D# (2011). Natural and experimental infection of Caenorhabditis nematodes by novel
viruses related to nodaviruses. PLoS Biol. 9, e1000586.
Bélicard T, Félix MA. Transmission multigénérationnelle de l'interférence à l'ARN chez le nématode C. elegans.
Médecine/sciences 2012 28:574-577.
Ashe A*, Bélicard T*, Le Pen J*, Sarkies P*, Frézal L, Lehrbach NJ, Félix MA#, Miska EA# (2013). A deletion
polymorphism in the C. elegans RIG-I homolog disables viral RNA dicing and antiviral immunity. eLife 2013
2:e00994. * co-first author, alphabetical order; # corresponding author.
Nom Prénom : BRESARD Gautier
Thèse commencée au 1 octobre 2012 et interrompue en décembre 2014, après avis du comité de thèse et de la
Direction de l'Ecole Doctorale (CdV).
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