GMGM - Génétique moléculaire, génomique, microbiologie - Université de Strasbourg https://gmgm.unistra.fr fr GMGM - Génétique moléculaire, génomique, microbiologie - Université de Strasbourg Sat, 20 Jul 2024 21:30:09 +0200 Sat, 20 Jul 2024 21:30:09 +0200 TYPO3 EXT:news news-16657 Mon, 10 Jun 2024 14:01:50 +0200 New publication in Nature Cell Biology by the MITO team in collaboration with the University of Liège /actualites/actualite/new-publication-in-nature-cell-biology-by-the-mito-team-in-collaboration-with-the-university-of-liege Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma.

doi.org/10.1038/s41556-024-01439-2

Transfer RNA dynamics contribute to cancer development through regulation of codon-specific messenger RNA translation. Specific aminoacyl-tRNA synthetases can either promote or suppress tumourigenesis. Here we show that valine aminoacyl-tRNA synthetase (VARS) is a key player in the codon-biased translation reprogramming induced by resistance to targeted (MAPK) therapy in melanoma. The proteome rewiring in patient-derived MAPK therapy-resistant melanoma is biased towards the usage of valine and coincides with the upregulation of valine cognate tRNAs and of VARS expression and activity. Strikingly, VARS knockdown re-sensitizes MAPK-therapy-resistant patient-derived melanoma in vitro and in vivo. Mechanistically, VARS regulates the messenger RNA translation of valine-enriched transcripts, among which hydroxyacyl-CoA dehydrogenase mRNA encodes for a key enzyme in fatty acid oxidation. Resistant melanoma cultures rely on fatty acid oxidation and hydroxyacyl-CoA dehydrogenase for their survival upon MAPK treatment. Together, our data demonstrate that VARS may represent an attractive therapeutic target for the treatment of therapy-resistant melanoma.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Tarassov-Smirnov Publications de l'Équipe Tarassov-Smirnov
news-16608 Thu, 30 May 2024 10:21:25 +0200 Nouvelle publication en collaboration /actualites/actualite/nouvelle-publication-en-collaboration-1 Natural proteome diversity links aneuploidy tolerance to protein turnover.
Julia Muenzner, Pauline Trébulle, Federica Agostini, Henrik Zauber, Christoph B. Messner, Martin Steger, Christiane Kilian, Kate Lau, Natalie Barthel, Andrea Lehmann, Kathrin Textoris-Taube, Elodie Caudal, Anna-Sophia Egger, Fatma Amari, Matteo De Chiara, Vadim Demichev, Toni I. Gossmann, Michael Mülleder, Gianni Liti, Joseph Schacherer, Matthias Selbach, Judith Berman, Markus Ralser.
Nature. 2024. doi: 10.1038/s41586-024-07442-9

Accessing the natural genetic diversity of species unveils hidden genetic traits, clarifies gene functions and allows the generalizability of laboratory findings to be assessed. One notable discovery made in natural isolates of Saccharomyces cerevisiae is that aneuploidy—an imbalance in chromosome copy numbers—is frequent (around 20%), which seems to contradict the substantial fitness costs and transient nature of aneuploidy when it is engineered in the laboratory. Here we generate a proteomic resource and merge it with genomic and transcriptomic data for 796 euploid and aneuploid natural isolates. We find that natural and lab-generated aneuploids differ specifically at the proteome. In lab-generated aneuploids, some proteins—especially subunits of protein complexes—show reduced expression, but the overall protein levels correspond to the aneuploid gene dosage. By contrast, in natural isolates, more than 70% of proteins encoded on aneuploid chromosomes are dosage compensated, and average protein levels are shifted towards the euploid state chromosome-wide. At the molecular level, we detect an induction of structural components of the proteasome, increased levels of ubiquitination, and reveal an interdependency of protein turnover rates and attenuation. Our study thus highlights the role of protein turnover in mediating aneuploidy tolerance, and shows the utility of exploiting the natural diversity of species to attain generalizable molecular insights into complex biological processes.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-16606 Thu, 30 May 2024 10:14:40 +0200 Nouvelle publication dans Nature Genetics /actualites/actualite/nouvelle-publication-dans-nature-genetics-1 Pan-transcriptome reveals a large accessory genome contribution to gene expression variation in yeast.
Élodie Caudal, Victor Loegler, Fabien Dutreux, Nikolaos Vakirlis, Élie Teyssonnière, Claudia Caradec, Anne Friedrich, Jing Hou, Joseph Schacherer.
Nature Genetics. 2024. doi: 10.1038/s41588-024-01769-9

Gene expression is an essential step in the translation of genotypes into phenotypes. However, little is known about the transcriptome architecture and the underlying genetic effects at the species level. Here we generated and analyzed the pan-transcriptome of ~1,000 yeast natural isolates across 4,977 core and 1,468 accessory genes. We found that the accessory genome is an underappreciated driver of transcriptome divergence. Global gene expression patterns combined with population structure showed that variation in heritable expression mainly lies within subpopulation-specific signatures, for which accessory genes are overrepresented. Genome-wide association analyses consistently highlighted that accessory genes are associated with proportionally more variants with larger effect sizes, illustrating the critical role of the accessory genome on the transcriptional landscape within and between populations.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-16505 Mon, 06 May 2024 10:11:35 +0200 Nouvelle publication dans PNAS /actualites/actualite/nouvelle-publication-dans-pnas-1 Species-wide quantitative transcriptomes and proteomes reveal distinct genetic control of gene expression variation in yeast.
Elie M Teyssonnière, Pauline Trébulle, Julia Muenzner, Joseph Schacherer.
PNAS. 2024. doi:10.1073/pnas.2319211121

Gene expression varies between individuals and corresponds to a key step linking genotypes to phenotypes. However, our knowledge regarding the species-wide genetic control of protein abundance, including its dependency on transcript levels, is very limited. Here, we have determined quantitative proteomes of a large population of 942 diverse natural Saccharomyces cerevisiae yeast isolates. We found that mRNA and protein abundances are weakly correlated at the population gene level. While the protein coexpression network recapitulates major biological functions, differential expression patterns reveal proteomic signatures related to specific populations. Comprehensive genetic association analyses highlight that genetic variants associated with variation in protein (pQTL) and transcript (eQTL) levels poorly overlap (3%). Our results demonstrate that transcriptome and proteome are governed by distinct genetic bases, likely explained by protein turnover. It also highlights the importance of integrating these different levels of gene expression to better understand the genotype–phenotype relationship.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-16241 Fri, 15 Mar 2024 09:43:39 +0100 Nouvelle publication en collaboration /actualites/actualite/nouvelle-publication-en-collaboration Absence of chromosome axis protein recruitment prevents meiotic recombination chromosome-wide in the budding yeast Lachancea kluyveri.
Sylvain Legrand, Asma Saifudeen, Hélène Bordelet, Julien Vernerey, Arnaud Guille, Amaury Bignaud, Agnès Thierry, Laurent Acquaviva, Maxime Gaudin, Aurore Sanchez, Dominic Johnson, Anne Friedrich, Joseph Schacherer, Matthew J Neale, Valérie Borde, Romain Koszul, Bertrand Llorente.
PNAS. 2024. doi:10.1073/pnas.2312820121

Meiotic recombination shows broad variations across species and along chromosomes and is often suppressed at and around genomic regions determining sexual compatibility such as mating type loci in fungi. Here, we show that the absence of Spo11-DSBs and meiotic recombination on Lakl0C-left, the chromosome arm containing the sex locus of the Lachancea kluyveri budding yeast, results from the absence of recruitment of the two chromosome axis proteins Red1 and Hop1, essential for proper Spo11-DSBs formation. Furthermore, cytological observation of spread pachytene meiotic chromosomes reveals that Lakl0C-left does not undergo synapsis. However, we show that the behavior of Lakl0C-left is independent of its particularly early replication timing and is not accompanied by any peculiar chromosome structure as detectable by Hi-C in this yet poorly studied yeast. Finally, we observed an accumulation of heterozygous mutations on Lakl0C-left and a sexual dimorphism of the haploid meiotic offspring, supporting a direct effect of this absence of meiotic recombination on L. kluyveri genome evolution and fitness. Because suppression of meiotic recombination on sex chromosomes is widely observed across eukaryotes, the mechanism for recombination suppression described here may apply to other species, with the potential to impact sex chromosome evolution.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-16111 Fri, 16 Feb 2024 12:06:18 +0100 Nouvelle publication de l'équipe /actualites/actualite/nouvelle-publication-de-lequipe Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast.
Andreas Tsouris, Gauthier Brach, Anne Friedrich, Jing Hou, Joseph Schacherer.
Mol Syst Biol. 2024. doi:10.1038/s44320-024-00021-0

Unraveling the genetic sources of gene expression variation is essential to better understand the origins of phenotypic diversity in natural populations. Genome-wide association studies identified thousands of variants involved in gene expression variation, however, variants detected only explain part of the heritability. In fact, variants such as low-frequency and structural variants (SVs) are poorly captured in association studies. To assess the impact of these variants on gene expression variation, we explored a half-diallel panel composed of 323 hybrids originated from pairwise crosses of 26 natural Saccharomyces cerevisiae isolates. Using short- and long-read sequencing strategies, we established an exhaustive catalog of single nucleotide polymorphisms (SNPs) and SVs for this panel. Combining this dataset with the transcriptomes of all hybrids, we comprehensively mapped SNPs and SVs associated with gene expression variation. While SVs impact gene expression variation, SNPs exhibit a higher effect size with an overrepresentation of low-frequency variants compared to common ones. These results reinforce the importance of dissecting the heritability of complex traits with a comprehensive catalog of genetic variants at the population level.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-16032 Tue, 30 Jan 2024 20:46:48 +0100 Nouvelle publication dans NAR /actualites/actualite/nouvelle-publcation-dans-nar Translation variation across genetic backgrounds reveals a post-transcriptional buffering signature in yeast.
Elie M Teyssonniere, Yuichi Shichino, Mari Mito, Anne Friedrich, Shintaro Iwasaki, Joseph Schacherer.
Nucleic Acids Research. 2024. doi:10.1093/nar/gkae030
 

Gene expression is known to vary among individuals, and this variability can impact the phenotypic diversity observed in natural populations. While the transcriptome and proteome have been extensively studied, little is known about the translation process itself. Here, we therefore performed ribosome and transcriptomic profiling on a genetically and ecologically diverse set of natural isolates of the Saccharomyces cerevisiae yeast. Interestingly, we found that the Euclidean distances between each profile and the expression fold changes in each pairwise isolate comparison were higher at the transcriptomic level. This observation clearly indicates that the transcriptional variation observed in the different isolates is buffered through a phenomenon known as post-transcriptional buffering at the translation level. Furthermore, this phenomenon seemed to have a specific signature by preferentially affecting essential genes as well as genes involved in complex-forming proteins, and low transcribed genes. We also explored the translation of the S. cerevisiae pangenome and found that the accessory genes related to introgression events displayed similar transcription and translation levels as the core genome. By contrast, genes acquired through horizontal gene transfer events tended to be less efficiently translated. Together, our results highlight both the extent and signature of the post-transcriptional buffering.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-15835 Fri, 19 Jan 2024 15:55:17 +0100 Nouvelle publication dans PLos Genetics /actualites/actualite/nouvelle-publication-dans-plos-genetics-1 Species-wide survey of the expressivity and complexity spectrum of traits in yeast.
Andreas Tsouris, Téo Fournier, Anne Friedrich, Jing Hou, Maitreya J. Dunham, Joseph Schacherer.

Assessing the complexity and expressivity of traits at the species level is an essential first step to better dissect the genotype-phenotype relationship. As trait complexity behaves dynamically, the classic dichotomy between monogenic and complex traits is too simplistic. However, no systematic assessment of this complexity spectrum has been carried out on a population scale to date. In this context, we generated a large diallel hybrid panel composed of 190 unique hybrids coming from 20 natural isolates representative of the S. cerevisiae genetic diversity. For each of these hybrids, a large progeny of 160 individuals was obtained, leading to a total of 30,400 offspring individuals. Their mitotic growth was evaluated on 38 conditions inducing various cellular stresses. We developed a classification algorithm to analyze the phenotypic distributions of offspring and assess the trait complexity. We clearly found that traits are mainly complex at the population level. On average, we found that 91.2% of cross/trait combinations exhibit high complexity, while monogenic and oligogenic cases accounted for only 4.1% and 4.7%, respectively. However, the complexity spectrum is very dynamic, trait specific and tightly related to genetic backgrounds. Overall, our study provided greater insight into trait complexity as well as the underlying genetic basis of its spectrum in a natural population.

]]>
Actualités du GMGM Actualités de l'Équipe Schacherer
news-15743 Thu, 18 Jan 2024 10:14:38 +0100 Strasbourg : à la recherche de la « super-bactérie » (DNA ; 17/01/24) /actualites/actualite/lequipe-aime-dans-les-dna-17-01-24 À l’université de Strasbourg, des chercheurs traquent les micro-organismes qui pourraient un jour gommer certains des micropolluants qui s’accumulent dans notre environnement. Ils ont déjà réussi à isoler une bactérie capable de digérer la molécule d’un médicament très utilisé. Actualités du GMGM Actualités de l'Équipe Vuilleumier news-15617 Mon, 15 Jan 2024 10:14:40 +0100 Nouvelle publication dans Cell Genomics /actualites/actualite/nouvelle-publication-dans-cell-genomics Non-additive genetic components contribute significantly to population-wide gene expression variation.
Andreas Tsouris, Gauthier Brach, Joseph Schacherer, Jing Hou.

Gene expression variation, an essential step between genotype and phenotype, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence gene expression variation remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originating from genetically divergent Saccharomyces cerevisiae isolates. Our analysis across 5,087 transcript abundance traits showed that non-additive components account for 36% of the gene expression variance on average. By comparing allele-specific read counts in parent-hybrid trios, we found that trans-regulatory changes underlie the majority of gene expression variation in the population. Remarkably, most cis-regulatory variations are also exaggerated or attenuated by additional trans effects. Overall, we showed that the transcriptome is globally buffered at the genetic level mainly due to trans-regulatory variation in the population.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-15575 Fri, 22 Dec 2023 11:24:15 +0100 Polluants éternels: en quête d'une bactérie mangeuse de PFAs (ARTE Info, 16 Décembre 2023) /actualites/actualite/polluants-eternels-en-quete-dune-bacterie-mangeuse-de-pfas-arte-16-decembre-2023 Actualités du GMGM Actualités de l'Équipe Vuilleumier news-15411 Wed, 22 Nov 2023 08:36:22 +0100 Montrer les invisibles du sol : dialogue entre étudiants en design et microbiologistes de l’équipe AIME du GMGM /actualites/actualite/montrer-les-invisibles-du-sol-dialogue-entre-etudiants-en-design-et-microbiologistes-de-lequipe-aime-du-gmgm Montrer les invisibles du sol :
dialogue entre étudiants en design et microbiologistes de l’équipe AIME du GMGM

14 octobre 2023 : ‘École Vivrière’ au CSC de la Roberstau à Strasbourg (https://www.lyceelecorbusier.eu/dsaa/?p=3730)

 

 

Les étudiant.e.s d’arts appliqués du Lycée le Corbusier à Illkirch ont eu l’occasion, dans le cadre de leur résidence de design, de dialoguer avec Dr. Emilie Muller et Dr. Françoise Bringel sur les invisibles du sol. Ces microorganismes ont fasciné par leur rôle dans l’environnement mais aussi par leur diversité de formes, de textures et de couleurs quand ils sont rendus visibles après culture (15 jours à 17°C) sur boite de Pétri, à partir d’empreintes de feuilles, ou d’étalement d’eaux de pluie, de rivière ou de mare, ou encore de suspension de sols et de compost (voir photos ci-contre). Le tout prélevé sur le site ou directement aux alentours, rendant tangibles les microbiomes du quotidien, d’ordinaire imperceptibles.

 

 

 

 

Afin de continuer à croiser les regards sur ce qu’est un sol, la soirée a été consacrée à un dialogue entre des professionnels et des curieux du sol : designers, artistes, botanistes, géologues, agents des espaces verts, maraîchers, microbiologistes, sociologues, notaires, enseignants et habitants. Dans une ambiance joueuse autant que sérieuse, le maître de cérémonie de ce premier conseil des sols a fait en sorte de nouer un dialogue sur cet objet dont la définition même est dépendante de l’interlocuteur !

]]>
Actualités du GMGM Actualités de l'Équipe Vuilleumier
news-15356 Tue, 14 Nov 2023 13:09:10 +0100 New publication of Emilie MULLER (team AIME) in Nature Ecology & Evolution /actualites/actualite/new-publication-of-emilie-muller-in-nature-ecology-evolution Microbiomes are essential for safeguarding health in humans and the environment, and are central to sustainability. A key microbiome-based technology is biological wastewater treatment, the most widely used biotechnological process on Earth. The process itself is subject to constant changes and does not fulfill the premise of sustainability. There is therefore an urgent need to predict the behaviour of its complex microbiomes to better control the process and to improve on its engineering. The Luxembourg Centre for Systems Biomedicine & the Department of Life Sciences and Medicine at the University of Luxembourg alongside with international collaborators has now developed a unique and novel modelling approach that can predict the dynamics and functions of such microbiomes several years into the future. This framework can also be applied to other key ecosystems, be it the human gut microbiome or pristine environments facing disturbance.


Research at University of Luxembourg, Norwegian University of Life Sciences, Medical University of Vienna, Centre National de La Recherche Scientifique (CNRS) & University of Strasbourg.
Funding by Luxembourg National Research Fund - FNR, European Research Council, European Commission, Austrian Science Fund FWF, Novo Nordisk Foundation & IBBL at  Luxembourg Institute of Health.

]]>
Actualités du GMGM Actualités de l'Équipe Vuilleumier
news-14855 Mon, 23 Oct 2023 16:14:07 +0200 Fête de la Science Lingolsheim 6 au 8 octobre 2023 /actualites/actualite/fete-de-la-science-lingolsheim-6-au-8-octobre-2023 GMGM a organisé et présenté la fête de la Science à Lingolsheim du 6 au 8 octobre 2023. Les membres de l'équipe Friant et Becker ont été impliqués dans divers ateliers :
- environnement: le monde des abeilles et de l'apithérapie
- écologie: la levure pour visualiser l'effet de cocktails de pesticides
- biodiversité: les champignons filamenteux, les observer et les comprendre
- Sciences participatives: Avec le jeu Mendeleieva, découvrez les éléments chimiques de votre vie de tous les jours et des femmes scientifiques étudiant ces éléments.

D'autres ateliers étaient proposés :
- santé: l'effet d'une carence alimentaire (régime) sur la physiologie d'une cellule
- le monde de l'ARN: construisez de l'ARN avec des bases aimantées
- neurosciences: NeuroBioCell, comprendre et observer le fonctionnement des cellules neuronales
- chimie: façonner les molécules pour en faire des micro-machines
- climat: la fresque du climat avec des étudiant-e-s de l'IUT de Schiltigheim
- Physique: l'Année de la Physique avec une exposition de femmes physiciennes
- Comité du Bas-Rhin de La Ligue contre le cancer (Ligue 67): la recherche contre le cancer, L’Agenda scolaire (ma santé, j’en prends soin), comment se protéger du cancer
- Sport dans le cadre des JO2024: Histoire du sport en Alsace

Et des conférences :

Conférence exceptionnelle de Jean-Pierre Sauvage, prix Nobel de chimie 2016

Mercredi 11 octobre à 20h00 : Gymnase Im Sand - Lingolsheim: réservation obligatoire

 

Rencontre-débat avec des sportifs médaillés et un préparateur physique professionnel

Mercredi 4 octobre à 20h00 : Maison des Arts de Lingolsheim "Science et condition physique : les sportifs de haut niveau", avec des sportifs médaillés et un préparateur physique professionnel (rugby, snowboard, tir paralympique) : avec Sylvain Dufour snowboard (Vainqueur de la Coupe du Monde 2014, Médaille d’argent aux Championnats du Monde 2009, 3 participations aux Jeux Olympiques, 4ième au JO d’hiver de 2018); Raphaël Voltz, tir à la carabine (Double vice-champion paralympique aux JO Pékin 2008, médaille d'argent JO Londres 2012, Double champion du monde) ; Romain Ritter, Préparateur physique Strasbourg Alsace Rugby. Animée par le Pr Michel Hasselmann.

 

Comprenez l'apport de la science dans le sport - conférences à la Maison des Arts de Lingolsheim à 20h00 :

  • 3 octobre : "Sport et santé": Cancer et activité physique : Dr Evelyne Lonsdorfer
  • 6 octobre: "Ocytocine : amour, sport et autres addictions sympathiques ...": Pr Marcel Hibert
  • 9 octobre: "Médecine, dopage et sport": Dr John Lenertz
  • 13 octobre: "Sports et Sciences": Créativité, partage et Joie de Vivre: Dr Pierre Antony

 

Rencontre-débat avec des scolaires sur l'histoire du sport en Alsace

Mardi 10 octobre à 14h30 : Avec Denis Jallat > Responsable du Comité de rédaction « histoire » de la revue Sciences sociales et sport. Sébastien Stumpp > Membre du Comité d’histoire des ministères chargés de la Jeunesse et des Sports (CHMJS) Cathy Blanc-Reibel > Ingénieure  CNRS

Pour public scolaire: primaires (CM1/CM2) et collèges - Gymnase Im Sand - Lingolsheim: réservation obligatoire

 

Table-Ronde: Sports, racisme et neuroscience - les comportements racistes dans le sport

Samedi 7 octobre à 14h00 : Gymnase Im Sand – Lingolsheim : avec Odile Rohmer Professeure en psychologie sociale - Jérôme Beauchez Professeur de sociologie et d'anthropologie à l'Université de Strasbourg - Daouada Ba > Président de la commission sport de la LICRA

 

]]>
Actualités du GMGM Focus du GMGM Actualités de l'Équipe Becker Actualités de l'Équipe Friant
news-14807 Mon, 16 Oct 2023 15:09:10 +0200 Bacteria, mitochondria, ribosomes & evolution at the Fête de la Science 2023 /actualites/actualite/bacteria-mitochondria-ribosomes-evolution-at-the-fete-de-la-science-2023 Friday, October 13, 2023 was the school day in the Village des Sciences, at the Palais Universitaire. The MITO team was there to familiarise the "youngest generation of scientists" with bases of cellular and molecular biology. Kids and adults from over 20 Alsatian schools discovered the amazing world of bacteria, mitochondria and ribosomes & their evolutionary journey. They could see (and smell!) real bacteria grown in the lab, play with structures of ribosomes to see how they changed over a billion years of evolution, and study electron microscopy photos to learn to recognise healthy and dysfunctional mitochondria.

]]>
Actualités du GMGM Actualités de l'Équipe Tarassov-Smirnov Focus de l'équipe Tarassov-Smirnov
news-14686 Fri, 15 Sep 2023 09:31:51 +0200 New publication by MITO-team /actualites/actualite/new-publication-by-mito-team Targeting of CRISPR-Cas12a crRNAs into human mitochondria BIOCHIMIE

Mitochondrial gene editing holds great promise as a therapeutic approach for mitochondrial diseases caused by mutations in the mitochondrial DNA (mtDNA). Current strategies focus on reducing mutant mtDNA heteroplasmy levels through targeted cleavage or base editing. However, the delivery of editing components into mitochondria remains a challenge. Here we investigate the import of CRISPR-Cas12a system guide RNAs (crRNAs) into human mitochondria and study the structural requirements for this process by northern blot analysis of RNA isolated from nucleases-treated mitoplasts. To investigate whether the fusion of crRNA with known RNA import determinants (MLS) improve its mitochondrial targeting, we added MLS hairpin structures at 3’-end of crRNA and demonstrated that this did not impact crRNA ability to program specific cleavage of DNA in lysate of human cells expressing AsCas12a nuclease. Surprisingly, mitochondrial localization of the fused crRNA molecules was not improved compared to non-modified version, indicating that structured scaffold domain of crRNA can probably function as MLS, assuring crRNA mitochondrial import. Then, we designed a series of crRNAs targeting different regions of mtDNA and demonstrated their ability to program specific cleavage of mtDNA fragments in cell lysate and their partial localization in mitochondrial matrix in human cells transfected with these RNA molecules. We hypothesize that mitochondrial import of crRNAs may depend on their secondary structure/sequence. We presume that imported crRNA allow reconstituting the active crRNA/Cas12a system in human mitochondria, which can contribute to the development of effective strategies for mitochondrial gene editing and potential future treatment of mitochondrial diseases.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Tarassov-Smirnov
news-14627 Mon, 04 Sep 2023 21:36:14 +0200 Nouvelle publication dans Nature Genetics /actualites/actualite/nouvelle-publication-dans-nature-genetics Telomere-to-telomere assemblies of 142 strains characterize the genome structural landscape in Saccharomyces cerevisiae.
Samuel O’Donnell, Jia-Xing Yue, Omar Abou Saada, Nicolas Agier, Claudia Caradec, Thomas Cokelaer, Matteo De Chiara, Stéphane Delmas, Fabien Dutreux, Téo Fournier, Anne Friedrich, Etienne Kornobis, Jing Li, Zepu Miao, Lorenzo Tattini, Joseph Schacherer, Gianni Liti, Gilles Fischer.

Pangenomes provide access to an accurate representation of the genetic diversity of species, both in terms of sequence polymorphisms and structural variants (SVs). Here we generated the Saccharomyces cerevisiae Reference Assembly Panel (ScRAP) comprising reference-quality genomes for 142 strains representing the species’ phylogenetic and ecological diversity. The ScRAP includes phased haplotype assemblies for several heterozygous diploid and polyploid isolates. We identified circa (ca.) 4,800 nonredundant SVs that provide a broad view of the genomic diversity, including the dynamics of telomere length and transposable elements. We uncovered frequent cases of complex aneuploidies where large chromosomes underwent large deletions and translocations. We found that SVs can impact gene expression near the breakpoints and substantially contribute to gene repertoire evolution. We also discovered that horizontally acquired regions insert at chromosome ends and can generate new telomeres. Overall, the ScRAP demonstrates the benefit of a pangenome in understanding genome evolution at population scale.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-14625 Mon, 04 Sep 2023 21:27:14 +0200 Nouvelle publication en collabration /actualites/actualite/nouvelle-publication-en-collabration Copy number variation alters local and global mutational tolerance.
Grace Avecilla, Pieter Spealman, Julia Matthews, Elodie Caudal, Joseph Schacherer, David Gresham.

Copy number variants (CNVs), duplications and deletions of genomic sequences, contribute to evolutionary adaptation but can also confer deleterious effects and cause disease. Whereas the effects of amplifying individual genes or whole chromosomes (i.e., aneuploidy) have been studied extensively, much less is known about the genetic and functional effects of CNVs of differing sizes and structures. Here, we investigated Saccharomyces cerevisiae (yeast) strains that acquired adaptive CNVs of variable structures and copy numbers following experimental evolution in glutamine-limited chemostats. Although beneficial in the selective environment, CNVs result in decreased fitness compared with the euploid ancestor in rich media. We used transposon mutagenesis to investigate mutational tolerance and genome-wide genetic interactions in CNV strains. We find that CNVs increase mutational target size, confer increased mutational tolerance in amplified essential genes, and result in novel genetic interactions with unlinked genes. We validated a novel genetic interaction between different CNVs and BMH1 that was common to multiple strains. We also analyzed global gene expression and found that transcriptional dosage compensation does not affect most genes amplified by CNVs, although gene-specific transcriptional dosage compensation does occur for ∼12% of amplified genes. Furthermore, we find that CNV strains do not show previously described transcriptional signatures of aneuploidy. Our study reveals the extent to which local and global mutational tolerance is modified by CNVs with implications for genome evolution and CNV-associated diseases, such as cancer.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-13759 Thu, 06 Jul 2023 07:47:41 +0200 Regards sur les ribozymes /actualites/actualite/regards-sur-les-ribozymes Benoït Masquida, directeur de recherche CNRS au laboratoire de Génétique moléculaire, génomique et microbiologie (GMGM) nous explique les multiples facettes des ribozymes, ARN capables d'activité catalytique. Actualités du GMGM Actualités de l'Équipe Becker Focus de l'équipe Becker news-13674 Mon, 19 Jun 2023 13:37:10 +0200 Nouvelle publication dans G3 /actualites/actualite/nouvelle-publication-dans-g3-1 Impact of the acquired subgenome on the transcriptional landscape in Brettanomyces bruxellensis allopolyploids.
Arthur Jallet, Anne Friedrich, Joseph Schacherer.
G3 Genes|Genomes|Genetics. 2023. doi:10.1093/g3journal/jkad115

Gene expression variation can provide an overview of the changes in regulatory networks that underlie phenotypic diversity. Certain evolutionary trajectories such as polyploidization events can have an impact on the transcriptional landscape. Interestingly, the evolution of the yeast species Brettanomyces bruxellensis has been punctuated by diverse allopolyploidization events leading to the coexistence of a primary diploid genome associated with various haploid acquired genomes. To assess the impact of these events on gene expression, we generated and compared the transcriptomes of a set of 87 B. bruxellensis isolates, selected as being representative of the genomic diversity of this species. Our analysis revealed that acquired subgenomes strongly impact the transcriptional patterns and allow discrimination of allopolyploid populations. In addition, clear transcriptional signatures related to specific populations have been revealed. The transcriptional variations observed are related to some specific biological processes such as transmembrane transport and amino acids metabolism. Moreover, we also found that the acquired subgenome causes the overexpression of some genes involved in the production of flavor-impacting secondary metabolites, especially in isolates of the beer population.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-13357 Mon, 17 Apr 2023 08:24:15 +0200 Prix de thèse 2022 de la SBS attribué à Théo Aspert /actualites/actualite/prix-de-these-2022-de-la-sbs-attribue-a-theo-aspert La Société de Biologie de Strasbourg (SBS) a décerné un prix à Théo Aspert pour sa thèse "Élucidation de la dynamique de vieillissement par micro-fluidique et apprentissage profond". Théo Aspert a soutenu sa thèse en 2022 sous la direction de Gilles Charvin. Il a présenté ses travaux pendant la cérémonie de remise des Prix de la SBS qui a eu lieu vendredi 21 avril 2023 de 13h00 à 18h30 à l’amphithéâtre du Collège Doctoral Européen, dans le cadre des Journées de L’Ecole Doctorale « Sciences de la Vie et de la Santé » de l’Université de Strasbourg.

DetecDiv, a generalist deep-learning platform for automated cell division tracking and survival analysis

Théo Aspert, Didier Hentsch, Gilles Charvin. eLife, (2022) - DOI: 10.7554/eLife.79519

 

]]>
Actualités du GMGM Actualités de l'Équipe Charvin
news-13213 Tue, 14 Mar 2023 12:37:19 +0100 Sylvie Friant aux Femin'Days au Lycée Leclerc de Saverne /actualites/actualite/sylvie-friant-aux-femindays-au-lycee-leclerc-de-saverne Actualités du GMGM Actualités de l'Équipe Friant news-12929 Mon, 16 Jan 2023 11:27:48 +0100 Nouvelle publication dans Genome Biology and Evolution /actualites/actualite/nouvelle-publication-dans-genome-biology-and-evolution Contrasting genomic evolution between domesticated and wild Kluyveromyces lactis yeast populations.
Anne Friedrich, Jean-Sébastien Gounot, Andreas Tsouris, Claudine Bleykasten, Kelle Freel, Claudia Caradec, Joseph Schacherer.
Genome Biology and Evolution. 2023. doi:10.1093/gbe/evad004

The process of domestication has variable consequences on genome evolution leading to different phenotypic signatures. Access to the complete genome sequences of a large number of individuals makes it possible to explore the different facets of this domestication process. Here, we sought to explore the genome evolution of Kluyveromyces lactis, a yeast species well-known for its involvement in dairy processes but also present in natural environments. Using a combination of short and long-read sequencing strategies, we investigated the genomic variability of 41 K. lactis isolates and found that the overall genetic diversity of this species is very high (θw = 3.3 × 10−2) compared to other species such as Saccharomyces cerevisiae (θw = 1.6 × 10−2). However, the domesticated dairy population shows a reduced level of diversity (θw = 1 × 10−3), probably due to a domestication bottleneck. In addition, this entire population is characterized by the introgression of the LAC4 and LAC12 genes, responsible for lactose fermentation and coming from the closely related species, Kluyveromyces marxianus, as previously described. Our results also highlighted that the LAC4/LAC12 gene cluster was acquired through multiple and independent introgression events. Finally, we also identified several genes that could play a role in adaptation to dairy environments through copy number variation. These genes are involved in sugar consumption, flocculation and drug resistance, and may play a role in dairy processes. Overall, our study illustrates contrasting genomic evolution and sheds new light on the impact of domestication processes on it.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-12925 Fri, 13 Jan 2023 20:01:45 +0100 Nouvelle publication dans PLoS Genetics /actualites/actualite/nouvelle-publication-dans-plos-genetics Lessons from the meiotic recombination landscape of the ZMM deficient budding yeast Lachancea waltii.
Fabien Dutreux, Abhishek Dutta, Emilien Peltier, Sabrina Bibi-Triki, Anne Friedrich, Bertrand Llorente, Joseph Schacherer.
PLoS Genet. 2023. doi:10.1371/journal.pgen.1010592

Meiotic recombination is a driving force for genome evolution, deeply characterized in a few model species, notably in the budding yeast Saccharomyces cerevisiae. Interestingly, Zip2, Zip3, Zip4, Spo16, Msh4, and Msh5, members of the so-called ZMM pathway that implements the interfering meiotic crossover pathway in S. cerevisiae, have been lost in Lachancea yeast species after the divergence of Lachancea kluyveri from the rest of the clade. In this context, after investigating meiosis in L. kluyveri, we determined the meiotic recombination landscape of Lachancea waltii. Attempts to generate diploid strains with fully hybrid genomes invariably resulted in strains with frequent whole-chromosome aneuploidy and multiple extended regions of loss of heterozygosity (LOH), which mechanistic origin is so far unclear. Despite the lack of multiple ZMM pro-crossover factors in L. waltii, numbers of crossovers and noncrossovers per meiosis were higher than in L. kluyveri but lower than in S. cerevisiae, for comparable genome sizes. Similar to L. kluyveri but opposite to S. cerevisiae, L. waltii exhibits an elevated frequency of zero-crossover bivalents. Lengths of gene conversion tracts for both crossovers and non-crossovers in L. waltii were comparable to those observed in S. cerevisiae and shorter than in L. kluyveri despite the lack of Mlh2, a factor limiting conversion tract size in S. cerevisiae. L. waltii recombination hotspots were not shared with either S. cerevisiae or L. kluyveri, showing that meiotic recombination hotspots can evolve at a rather limited evolutionary scale within budding yeasts. Finally, L. waltii crossover interference was reduced relative to S. cerevisiae, with interference being detected only in the 25 kb distance range. Detection of positive inference only at short distance scales in the absence of multiple ZMM factors required for interference-sensitive crossovers in other systems likely reflects interference between early recombination precursors such as DSBs.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-12871 Tue, 20 Dec 2022 15:56:02 +0100 The MITO team created an innovative subcellular transcriptomics approach, CoLoC-seq - Nucleic Acids Research /actualites/actualite/the-mito-team-created-an-innovative-subcellular-transcriptomics-approach-coloc-seq-nucleic-acids-research A new genome-wide method that marries classical enzymatic kinetics, deep sequencing, and mathematical modelling - CoLoC-seq - has been created in the MITO team and successfully applied to human mitochondria to tell resident RNAs from contaminants. Damien Jeandard, Anna Smirnova, Akinyemi Mandela Fasemore, Léna Coudray, Nina Entelis, Konrad U Förstner, Ivan Tarassov, Alexandre Smirnov (2023) CoLoC-seq probes the global topology of organelle transcriptomesNucleic Acids Research 51:e16.

Proper RNA localisation is essential for physiological gene expression. Various kinds of genome-wide approaches permit to comprehensively profile subcellular transcriptomes. Among them, cell fractionation methods, that couple RNase treatment of isolated organelles to the sequencing of protected transcripts, remain most widely used, mainly because they do not require genetic modification of the studied system and can be easily implemented in any cells or tissues, including in non-model species. However, they suffer from numerous false-positives since incompletely digested contaminant RNAs can still be captured and erroneously identified as resident transcripts. Here we introduce Controlled Level of Contamination coupled to deep sequencing (CoLoC-seq) as a new subcellular transcriptomics approach that efficiently bypasses this caveat. CoLoC-seq leverages classical enzymatic kinetics and tracks the depletion dynamics of transcripts in a gradient of an exogenously added RNase, with or without organellar membranes. By means of straightforward mathematical modelling, CoLoC-seq infers the localisation topology of RNAs and robustly distinguishes between genuinely resident, luminal transcripts and merely abundant surface-attached contaminants. Our generic approach performed well on human mitochondria and is in principle applicable to other membrane-bounded organelles, including plastids, compartments of the vacuolar system, extracellular vesicles, and viral particles.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Tarassov-Smirnov Publications de l'Équipe Tarassov-Smirnov
news-12803 Tue, 29 Nov 2022 13:50:18 +0100 Un ARN pour détecter le fluor ouvrant la porte vers le développement d’enzymes de dépollution /actualites/actualite/un-arn-pour-detecter-le-fluor-ouvrant-la-porte-vers-le-developpement-denzymes-de-depollution Retrouvez la dernière publication (doi.org/10.1002/smll.202205232) de Claire HUSSER et de Michael RYCKELYNCK (équipe « Biologie Digitale de l’ARN ») en ligne sur le site du journal Small. Ce travail, réalisé en collaboration avec Stéphane VUILLEUMIER (équipe “Adaptations et interactions des microorganismes dans l’environnement”, GMGM, Université de Strasbourg – CNRS), présente le développement de « FluorMango », un biosenseur ARN capable d’émettre une fluorescence exclusivement en présence d’ion fluorure. Cette molécule est le premier biosenseur permettant de détecter de façon directe, dynamique et biocompatible la présence de fluorure. Les auteurs ont ainsi pu mesurer en temps réel la dégradation d’un composé fluoré (le fluoracétate) par l’activité enzymatique contenue dans des cellules vivantes. Réalisé dans le cadre du projet ANR « MicroFluor », ce développement est un pas important vers la découverte de nouvelles enzymes de dépollution par criblage fonctionnel de populations microbiennes issues d’échantillons environnementaux ou de banque de gènes. Parmi les activités cibles, des enzymes capables des dégrader les Substances Alkyl (Poly)Perfluorées (PFAS), une large famille de composés extrêmement stables et toxiques, produits industriellement en grandes quantités et retrouvés de manière croissante dans l’environnement.

]]>
Actualités du GMGM Actualités de l'Équipe Vuilleumier
news-12783 Thu, 24 Nov 2022 11:04:58 +0100 Article dans le magazine Savoir(s) : Une bactérie pour manger un médicament antidiabétique, micropolluant de l’environnement. /actualites/actualite/une-bacterie-pour-manger-un-medicament-antidiabetique-micropolluant-de-lenvironnement-article-dans-savoirs

Au-delà des polluants majeurs comme les hydrocarbures et les solvants, notre mode de vie diffuse dans l’environnement des polluants pharmaceutiques, appelés micropolluants en raison des concentrations très faibles auxquelles ils sont rencontrés, que les stations d’épuration parviennent encore mal à éliminer. En s’intéressant à cette problématique, l’équipe de Stéphane Vuilleumier, chercheur au laboratoire de Génétique moléculaire, génomique, microbiologie (GMGM – CNRS / Unistra), est parvenue à isoler une bactérie capable de se nourrir d'un des agents antidiabétiques les plus prescrits au monde, la metformine.

 

Article de Savoir(s) : Une bactérie pour manger un médicament antidiabétique, micropolluant de l’environnement

]]>
Actualités du GMGM Actualités de l'Équipe Vuilleumier
news-12772 Tue, 22 Nov 2022 13:44:34 +0100 Nouvelle publication équipe AIME : une bactérie se nourrissant de metformine, antidiabétique et contaminant aquatique majeur /actualites/actualite/nouvelle-publication-equipe-aime-une-bacterie-se-nourrissant-de-metformine-antidiabetique-et-contaminant-aquatique-majeur A Methylotrophic Bacterium Growing with the Antidiabetic Drug, Metformin as Its Sole Carbon, Nitrogen and Energy Source. Chaignaud, Gruffaz, et al. Microorganisms 2022, 10, 2302. https://doi.org/10.3390/microorganisms10112302 La metformine est un médicament de première intention contre le diabète de type II et l'un des agents antidiabétiques les plus prescrits dans le monde (150 millions de personnes). Il est également envisagé pour d'autres applications thérapeutiques, y compris le cancer et les troubles endocriniens. La metformine reste largement non métabolisée par les enzymes humaines. À des doses quotidiennes de 0,5 à 2,5 g par patient, il est devenu un micropolluant dominant dans les stations d'épuration des eaux usées et les milieux aquatiques. Ses effets toxiques sont encore débattus, avec des effets néfastes signalés chez les organismes aquatiques et potentiellement aussi chez l'homme.
 Les micro-organismes sont ici en première ligne, avec leur capacité à développer la capacité de transformer enzymatiquement les contaminants chimiques, et de tolérer leurs effets toxiques. Le métabolisme microbien des composés à un atome de carbone ou dépourvus de liaisons carbone-carbone est à même de jouer un rôle-clé dans la dégradation de nombreux produits pharmaceutiques tels que la metformine, dont les atomes de carbone sont exclusivement liés à des atomes d'autres éléments.
 À notre connaissance, aucun micro-organisme capable d'utiliser la metformine comme source de carbone et d'azote pour la croissance n'avait encore été signalé. Nous décrivons ici la souche Aminobacter niigataensis MD1, une bactérie méthylotrophe aérobie capable d'utiliser la metformine comme seule source de carbone, d'azote et d'énergie pour sa croissance et isolée à partir de boues activées de la station d'épuration de la Ville de Strasbourg. Le génome de la souche MD1 a été séquencé, son métabolisme de la metformine a été étudié en détail par transcriptomique et protéomique, et les gènes impliqués dans la croissance avec la metformine ont été identifiés. Les résultats obtenus suggèrent une évolution récente de la capacité de la souche MD1 à dégrader la metformine pour sa croissance.

]]>
Actualités du GMGM Actualités de l'Équipe Vuilleumier
news-12765 Mon, 21 Nov 2022 15:40:05 +0100 MITO team : editorial in Frontiers Physiology /actualites/actualite/mito-team-editorial-in-frontiers-physiology Editorial for a special issue of Frontiers Physiology Burzio VA, Barrey E, Leucci E, Entelis N,
Hollander JM and Das S (2022)
Editorial:
Role of mitochondria-associated noncoding
RNAs inintracellular communication.
Front. Physiol. 13:980674.
doi: 10.3389/fphys.2022.980674
 

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Tarassov-Smirnov Publications de l'Équipe Tarassov-Smirnov
news-12713 Mon, 14 Nov 2022 11:05:46 +0100 New publication of the MITO team in Computational and Structural Biotechnology Journal /actualites/actualite/new-publication-of-the-mito-team-in-computational-and-structural-biotechnology-journal Theoretical and mathematical biology paper about hub-centred RNA-protein networks Smirnov A (2022) How global RNA-binding proteins coordinate the behaviour of RNA regulons: an information approach. Comput Struct Biotechnol J doi:10.1016/j.csbj.2022.11.019

RNA-binding proteins are central players in post-transcriptional regulation. Some of them, such as the well-studied bacterial RNA chaperones Hfq and ProQ or the eukaryotic RNAi factor Argonaute, interact with hundreds-to-thousands of different RNAs and thereby globally affect gene expression. As a shared yet limited resource, these and other RNA-binding hubs drive strong competition between their multiple ligands. This creates a ground for significant cross-communication between RNA targets, which enables them to share information, “synchronise” their behaviour, and produce interesting biochemical effects, sometimes propagating across the highly connected RNA-protein network. This property is likely universally present in hub-centred networks and plays a key role in global gene expression programmes. It is also an important factor in biotechnology and synthetic biology applications of RNA/protein-based circuits. However, few studies so-far focused on describing and explaining this phenomenon from first principles. Here we introduce an information theory-based framework to comprehensively and exactly describe information flow in hub-centred networks. We show that information sharing can achieve significant levels in relatively small networks, provided the hub is present in limiting concentrations. The transmitted information is sufficient to noticeably affect the binding probabilities of competing targets but drops exponentially along the network. Target overexpression can disrupt communication between other targets, while hub sequestration boosts the crosstalk. We also find that overlaps between the interactomes of two different hubs create both entropic challenges and new forms of long-range communication between RNAs and proteins.

]]>
Actualités du GMGM Publications du GMGM Actualités de l'Équipe Tarassov-Smirnov Publications de l'Équipe Tarassov-Smirnov