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Cellular and Developmental Plasticity in Regenerating and Aging Hydra

English title Cellular and Developmental Plasticity in Regenerating and Aging Hydra
Applicant Galliot Brigitte
Number 169930
Funding scheme Project funding (Div. I-III)
Research institution Département de Génétique et Evolution Faculté des Sciences Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Embryology, Developmental Biology
Start/End 01.11.2016 - 31.10.2019
Approved amount 635'829.00
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All Disciplines (4)

Discipline
Embryology, Developmental Biology
Biochemistry
Cellular Biology, Cytology
Molecular Biology

Keywords (9)

Hydra model system; epithelial cell plasticity; quantitative RNA-seq transcriptomics; injury-induced ROS signaling; autophagy; low senescence and aging; regeneration and wound healing; adult somatic stem cells; evolution

Lay Summary (French)

Lead
Les Hydres d’eau douce sont un modèle unique pour disséquer les mécanismes qui maintiennent des animaux capables de régénérer à tout âge, de s’adapter à un jeûne prolongé ou à la perte des cellules souches qui produisent le système neuro-sensoriel (i-cells). Les animaux sans neurogénèse deviennent “épithéliaux” et nous avons montré que les cellules épithéliales restantes s’adaptent en sur-exprimant des gènes impliqués dans la neurogénèse, la neurotransmission ou la reprogrammation cellulaire (Wenger et al. 2016). Avec ce nouveau projet, nous voulons caractériser le rôle de gènes de “reprogrammation” chez l’hydre et dans des cellules de mammifères.
Lay summary

Cependant certaines souches d’hydres ne s’adapte pas à la perte des i-cells, ces animaux montrant rapidement des signes de vieillissement (perte de dynamisme, de régénération, de renouvellement des cellules souches), et meurent en trois mois (Tomczyk et al. 2015). Ici, un mécanisme de survie essentiel appelé “autophagie" est déficient. Des marqueurs d’autophagie s’accumulent, signant l’incapacité des cellules à réguler la protéostase, de façon très similaire à ce qui est observé au cours du vieillissement humain. Nous proposons d’analyser le rôle de ces régulateurs de protéostase chez l’hydre vieillissante.

La régénération est possible grâce à la transformation en quelques heures du tissue gastrique en un centre organisateur qui va instruire les cellules avoisinantes pour régénérer une nouvelle tête. Cette activité du centre organisateur dépend de deux composants, activateur identifié comme le facteur de croissance Wnt3, et inhibiteur, resté inconnu jusqu’à présent. Nous avons identifié des candidats inhibiteurs et planifions de les tester chez l’hydre et chez le poisson-zèbre. 

Direct link to Lay Summary Last update: 04.10.2016

Lay Summary (English)

Lead
The freshwater Hydra polyps provide a unique model system to investigate the mechanisms that maintain an adult animal fit over the years, able to regenerate and to adapt to harsh conditions such as prolonged starvation or loss of neurogenesis. Animals that lose their interstitial stem cells (i-cells) do not produce neurons anymore, becoming “epithelial”. Such animals are able to survive and regenerate if force-fed. We showed that epithelial cells in Hydra vulgaris adapt by overexpressing genes exhibiting potential neurogenic, neurotransmission or reprogramming functions (Wenger et al. 2016).
Lay summary

We now wish to characterize the regulators of epithelial plasticity and the role of several candidates will be tested in Hydra vulgaris and in mammalian cells. In parallel we showed that this property of epithelial plasticity is lacking in some strain (Ho_CS). As a consequence of the loss of i-cells, Ho_CS animals rapidly develop an aging phenotype, characterized by the loss of fitness, regeneration and stem cell renewal, and die within three months (Tomczyk et al. 2015). Here an essential survival / recycling process named autophagy is deficient, as evidenced by the accumulation of specific markers of autophagy, which are a hallmark of deficient proteostasis as observed in human aging. We plan to investigate the tole of these markers in aging Hydra.

Regeneration is possible as any gastric tissue can convert to an organizer center that instructs surrounding tissues to form a new head. The activity of the head organizer center relies on two components, activator identified as Wnt3 by the Holstein lab, and inhibitor, unknown so far. We have identified a candidate inhibitor that we plan to test in Hydra and in zebrafish. 

Direct link to Lay Summary Last update: 04.10.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Model systems for regeneration: Hydra
Vogg Matthias C., Galliot Brigitte, Tsiairis Charisios D. (2019), Model systems for regeneration: Hydra, in Development, 146(21), dev177212-dev177212.
Modern genomic tools reveal the structural and cellular diversity of cnidarian nervous systems
Rentzsch Fabian, Juliano Celina, Galliot Brigitte (2019), Modern genomic tools reveal the structural and cellular diversity of cnidarian nervous systems, in Current Opinion in Neurobiology, 56, 87-96.
Loss of neurogenesis in aging Hydra
Tomczyk Szymon, Buzgariu Wanda, Perruchoud Chrystelle, Fischer Kathleen, Austad Steven, Galliot Brigitte (2019), Loss of neurogenesis in aging Hydra, in Developmental Neurobiology, dneu.22676-dneu.22676.
Generic and context-dependent gene modulations during Hydra whole body regeneration
Wenger Yvan, Buzgariu Wanda, Perruchoud Christelle, Loichot Gregory, Galliot Brigitte (2019), Generic and context-dependent gene modulations during Hydra whole body regeneration, BioRxiv, Cold Spring Harbor, USA.
An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra
Vogg Matthias C., Beccari Leonardo, Iglesias Ollé Laura, Rampon Christine, Vriz Sophie, Perruchoud Chrystelle, Wenger Yvan, Galliot Brigitte (2019), An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra, in Nature Communications, 10(1), 312-312.
Non-developmental dimensions of adult regeneration in Hydra
Galliot Brigitte, Buzgariu Wanda, Schenkelaars Quentin, Wenger Yvan (2018), Non-developmental dimensions of adult regeneration in Hydra, in The International Journal of Developmental Biology, 62(6-7-8), 373-381.
Impact of cycling cells and cell cycle regulation on Hydra regeneration
Buzgariu Wanda, Wenger Yvan, Tcaciuc Nina, Catunda-Lemos Ana-Paula, Galliot Brigitte (2018), Impact of cycling cells and cell cycle regulation on Hydra regeneration, in Developmental Biology, 433(2), 240-253.
Hydra , a Model System for Deciphering the Mechanisms of Aging and Resistance to Aging
Schenkelaars Quentin, Tomczyk Szymon, Wenger Yvan, Ekundayo Kazadi, Girard Victor, Buzgariu Wanda, Austad Steve, Galliot Brigitte (2018), Hydra , a Model System for Deciphering the Mechanisms of Aging and Resistance to Aging, in Ram Jeffrey, Conn P. Michael (ed.), Academic Press, USA, 507-520.
Deficient autophagy drives aging in Hydra
Tomczyk Szymon, Schenkelaars Quentin, Suknovic Nenad, Wenger Yvan, Ekundayo Kazadi, Buzgariu Wanda, Bauer Christoph, Fischer Keyt, Austad Stephen, Galliot Brigitte (2017), Deficient autophagy drives aging in Hydra, BioRxiv, Cold Spring Harbor, USA.
Hydra, a model system for deciphering the mechanisms of aging and resistance to aging
Schenkelaars Quentin, Tomczyk Szymon, Wenger Yvan, Ekundayo Kazadi, Girard Victor, Buzgariu Wanda, Austad Stephen, Galliot Brigitte (2017), Hydra, a model system for deciphering the mechanisms of aging and resistance to aging, BioRxiv, Cold Spring Harbor, USA.
Trends in tissue repair and regeneration
Galliot Brigitte, Crescenzi Marco, Jacinto Antonio, Tajbakhsh Shahragim (2017), Trends in tissue repair and regeneration, in Development, 144(3), 357-364.
Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells
Wenger Y., Buzgariu W., Galliot B. (2016), Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells, in Philosophical Transactions of the Royal Society B: Biological Sciences, 371(1685), 20150040-20150040.
How Somatic Adult Tissues Develop Organizer Activity
Vogg Matthias C., Wenger Yvan, Galliot Brigitte (2016), How Somatic Adult Tissues Develop Organizer Activity, in Wassarman Paul (ed.), Elsevier, New York, USA, 391-414.
Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra
TomczykSzymon, SuknovicNenad, SchenkelaarQuentin, WengerYvan, EkundayoKazadi, BuzgariuWanda, BauerChristoph, FischerKathleen, AustadSteeves, GalliotBrigitte, Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra, in Development.

Datasets

Hydra Draft genomes of two Hydra species

Author Wenger, Yvan
Publication date 29.01.2019
Persistent Identifier (PID) PRJNA419866
Repository Bioproject
Abstract
Genome sequencing and draft assembly of two Hydra species, Hydra oligactis and Hydra viridissima

Hydra vulgaris Jussy reference transcriptome

Author Wenger, Yvan
Publication date 23.08.2017
Persistent Identifier (PID) PRJNA399692
Repository Bioproject
Abstract
Transcriptome or Gene expression, monoisolate, Reference transcriptome for the Hydra vulgaris strain JussyAll sequences and expression profiles are available on the server Hydratlas.unige.ch

Hydra vulgaris AEP reference transcriptome

Author Wenger, Yvan
Publication date 18.09.2017
Persistent Identifier (PID) PRJNA407749
Repository Bioproject
Abstract
Transcriptome assembly obtained using a mix of animals from thee different transgenic lines expressing GFP (described in Hemmrich et al., Mol Biol Evol, 2012).All sequences and expression patterns are available on the server Hydratlas.unige.ch

Generic and context-dependent gene modulations during Hydra whole body regeneration

Author Galliot, Brigitte
Publication date 07.03.2018
Persistent Identifier (PID) PRJNA437305
Repository Bioproject
Abstract
Umbrella project; This SuperSeries is composed of the SubSeries listed below. Overall design: Refer to individual SeriesPRJNA437307: Gene expression time course analysis during apical and basal regeneration in Hydra (B. Galliot, Genetics and...) _Hydra vulgarisPRJNA437308: Gene expression after depletion of fast cycling cells by heat shock, hydroxyurea, or colchicine treatment in the Sf-1 thermosensitive Hydra strain. (B. Galliot, Genetics and...) _Hydra vulgarisPRJNA437309: Gene expressions in the three Hydra stem cell populations (B. Galliot, Genetics and...)_Hydra vulgarisAll sequences and expression profiles are available on the server Hydratlas.unige.ch

Gene expression time course analysis during apical and basal regeneration in Hydra

Author Galliot, Brigitte
Publication date 07.03.2018
Persistent Identifier (PID) PRJNA437307
Repository Bioproject
Abstract
Overall design: Samples were taken from regenerating tips of Hydra regenerating apical regions from the 50% (mid-gastric position) or the 80% level (i.e. after decapitation), as well as basal-regenerating tips from the 50% position. Data were sampled at 0, 0.5, 1, 2, 4, 8, 16, 24,36,48 hours post section. In addition, intact animals, apical regions (head), and basal regions (basal disk and lower part of the peduncle) were sampled in homeostatic condition. All samples were produced in biological triplicates from tissue originating from 20 to 25 animals.The processed data deposited here are also accessible in a graphical manner from a blast-based web interface available at https://hydratlas.unige.ch

Gene expression after depletion of fast cycling cells by heat shock, hydroxyurea, or colchicine treatment in the Sf-1 thermosensitive Hydra strain

Author Galliot, Brigitte
Publication date 07.03.2018
Persistent Identifier (PID) PRJNA437308
Repository Bioproject
Abstract
Animals from the thermosensitive mutant strain Hydra Sf-1 (also called Hydra magnipapillata A9) were subjected to heat shock, hydroxyurea, or colchicine treatment and were sampled 9 (colchicine, heat shock) or 11 days (hydroxyurea) after the beginning of the treatment. In addition, animals treated with hydroxurea were sampled at 4, 5, and 7 days after the beginning of the treatment. Central body columns were used for sequencing. Most conditions are represented by 3 or 4 replicates. All sequences and expression profiles are available on Hydratlas.unige.ch

Gene expressions in the three Hydra stem cell populations

Author Galliot, Brigitte
Publication date 07.03.2018
Persistent Identifier (PID) PRJNA437309
Repository Bioproject
Abstract
Transgenics Hydra reported by Hemmrich et al. (2012) expressing eGFP in interstitial stem-cells (ISC), gastrodermal epithelial cells (gESC) or epidermal epithelial cells (eESC) were used to sort these populations of stem cells by Fluorescence activated cell sorting (FACS) and perform RNA-seq on enriched populations. The processed data deposited here are also accessible in a graphical manner from a blast-based web interface available at https://hydratlas.unige.ch Overall design: Three or four replicates per sample, variable number of days of starvation.All sequences and expression profiles are available on Hydratlas.unige.ch

Human (RNA-seq) An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra

Author Beccari, Leo
Publication date 16.10.2018
Persistent Identifier (PID) PRJNA497062
Repository Bioproject
Abstract
Transcriptome or Gene expression in the human HEK293T cells Dataset listing the genes differentially expressed between HySp5 vs HySp5-ΔDBD or between ZfSp5a vs ZfSp5a-ΔDBD. Three samples per condition

Epigenomics: Sp5 ChIP-Seq on the human genome

Author Beccari, Leo
Persistent Identifier (PID) PRJNA497061
Repository Bioproject
Abstract
Epigenomics: Analysis of the binding sites of HySp5 and ZfSp5a overexpressed in the HEK293T cells. The total HySp5 and ZfSp5a coverages (in Mb) and of the frequency distribution of the number of Sp5-enriched regions per gene were performed in R using personalized scripts.

Umbrella project human cells expressing Sp5 (ChI-seq and RNA-seq)

Author Beccari, Leo
Publication date 16.10.2018
Persistent Identifier (PID) PRJNA497058
Repository Bioproject
Abstract
This SuperSeries is composed of the SubSeries listed below:Umbrella project covering the ChIP-seq human dataset (PRJNA497061) and the RNA-seq human dataset (PRJNA497062) HEK293T cells

Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing

Author Beccari, Leo
Publication date 16.10.2018
Persistent Identifier (PID) GSE121321
Repository GEO database
Abstract
This SuperSeries is composed of the SubSeries listed below.This SuperSeries is composed of the following SubSeries:GSE121316 An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra [ChIP-Seq]GSE121317 An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra [RNA-Seq]

ChIP seq analysis of Sp5 occupancies in human HEK293 cells expressing either Hydra Sp5 or Zebrafish Sp5 proteins

Author Beccari, Leo
Publication date 16.10.2018
Persistent Identifier (PID) GSE121316
Repository GEO database
Abstract
Genome binding/occupancy profiling by high throughput sequencingChIP seq analysis of Sp5 occupancies in human HEK293 cells transfected with expression vectors coding either for Hydra Sp5 or Zebrafish Sp5 proteins.The genomic occupancies mutant versions of these proteins lacking the Sp5 DNA binding domain were also tested. EAch experimental conditions was tested in 2 independent biological replicates.

Expression profiling of HEK293T cells expressing HySp5, HySp5-dDBD, ZfSp5 and ZfSp5-dDBD by high throughput sequencing

Author Beccari, Leo
Publication date 16.10.2018
Persistent Identifier (PID) GSE121317
Repository GEO database
Abstract
Expression profiling by high throughput sequencingCells were transfected either with a control plasmid or with plasmids encoding for HySp5 and ZfSp5a proteins. Plasmids encoding for mutant versions of these genes, lacking the DNA binding domain (HySp5-dDBD and ZfSp5-dDBD respectively), were also transfected. In order to evaluate the ability of HySP5 and ZfSp5a proteins to regulate gene expression via cooperation with beta-catenin, HEK293 cells were cotransfected with a combination of plasmids encoding for these factors. HEK293 cells were also transfected either with the b-CATENIN coding plasmid alone or with a combination of plasmids encoding for HySp5-dDBD or ZfSp5-dDBD together with b-catenin.

Collaboration

Group / person Country
Types of collaboration
Joliot & Vriz lab, Collège de France France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Denis Martinvalet, CMU Genève Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Leo Beccari (Duboule lab, Genève) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
8th annual meeting of iGE3 Talk given at a conference Identification of Sp5 regulation and Sp5 target genes 04.11.2019 Geneva, Switzerland Iglesias Olle Laura;
FEBS 2019 Advanced course, Ageing and Regeneration Talk given at a conference Ageing and regeneration in Hydra, the impact of autophagy on stem cell behavior 09.09.2019 Innsbruck, Austria Galliot Brigitte;
Embryology course, Marine Biological Laboratory, Woods Hole - 2019 - Individual talk Hydra, a model system for adult developmental biology 08.07.2019 Woods Hole, MA, United States of America Galliot Brigitte;
Gordon Research Conference: Tissue Repair and Regeneration 2019 Talk given at a conference Mechanisms of Regeneration in Hydra 09.06.2019 New London, NH, United States of America Galliot Brigitte;
Colloque Collège de France 2019: Development and Regeneration, same mechanisms, same concepts? Talk given at a conference An Evolutionary-Conserved Repressor of Wnt Signaling Controls Head Regeneration in Hydra 16.05.2019 Paris, France Galliot Brigitte;
University of Barcelona, PhD program 2019 Individual talk Genetic dissection of the Hydra head organizer 12.04.2019 Barcelona, Spain Galliot Brigitte;
11TH BIOPHD CONFERENCE 2019 Poster Inhibition of the Hydra head organizer 27.03.2019 Schwarzsee, Switzerland Iglesias Olle Laura;
Guest Seminars SARS International Centre for Marine Molecular Biology & Uni Bergen, 2019 Individual talk Hydra, a model for regeneration and slow aging 15.02.2019 Bergen, Norway Galliot Brigitte;
Development and stem cells in plants and animals ENS Lyon - 2018 - Individual talk Hydra a model system for regeneration and aging studies 28.11.2018 Lyon, France Galliot Brigitte;
EMBO Workshop on Tissue Repair and Regeneration 2018 Poster Symmetrical versus asymmetrical ROS signaling in Hydra regenerating tips 15.09.2018 Valette, Malta Suknovic Nenad;
Cnidaria Evo-Devo satellite meeting, 7th Euro Evo Devo Meeting - Gallway 2018 - Talk given at a conference Hydra, a model for regeneration and aging 25.06.2018 Gallway, Ireland Galliot Brigitte;
Embryology course, Marine Biological Laboratory, Woods Hole - 2018 - Individual talk Epithelial plasticity in Regenerating and Aging Hydra 18.06.2018 Woods Hole, MA, US, United States of America Galliot Brigitte;
1st AsiaEvo conference - Shenzhen 2018 - Talk given at a conference Can epithelial plasticity compensate for deficient neurogenesis ? 18.04.2018 Shenzhen, China Galliot Brigitte;
LS2 Annual Meeting 2018 Poster Autophagy deficiency in aging Hydra 12.02.2018 Lausanne, Switzerland Tomczyk Szymon;
COST Maristem 1st Meeting - Piran 2018 - Talk given at a conference Hydra, a model to study the impact of autophagy on stem cells 05.02.2018 Piran, Slovenia Galliot Brigitte;
10th International PhD program Conference 2018 Poster Injury-induced ROS signaling in regenerating Hydra 31.01.2018 Leukerbad, Switzerland Suknovic Nenad;
10th International PhD Program Conference 2018 Talk given at a conference Structure and role of the Hippo pathway in intact and regenerating Hydra 31.01.2018 Leukerbad, Switzerland Al Haddad Sarah;
International Workshop Origins of Metazoans - Paris 2017 - Talk given at a conference The Developmental and Non-developmental Aspects of Regeneration in Early Metazoan Evolution 07.11.2017 Paris, France Galliot Brigitte; Schenkelaars Quentin;
Ecole doctorale, Centre de Biologie Intégrative TOULOUSE - 2017 - Individual talk The Developmental and Non-developmental Aspects of Regeneration 20.10.2017 Toulouse, France Galliot Brigitte;
9th International PhD Program Conference 2017 Poster Structure and role of the Hippo pathway in Hydra 18.10.2017 Montreux, Switzerland Al Haddad Sarah;
9th International Meeting of the LASDB - Medellin 2017 Talk given at a conference Regeneration and Slow Aging, What Role for Autophagy ? 09.10.2017 Medellin, Colombia Galliot Brigitte;
Satellite Courses of the 9th LASDB Meeting- Medellin 2017 Individual talk Hydra a model system for adult developmental biology 05.10.2017 Medellin, Colombia Galliot Brigitte;
13th annual SSCN meeting - Lausanne 2017 - Talk given at a conference Regeneration and Slow Aging, What Role for Autophagy ? 05.09.2017 Lausanne, Switzerland Galliot Brigitte;
Embryology course, Marine Biological Laboratory, Woods Hole - 2017 - Individual talk Epithelial plasticity in Regenerating and Aging Hydra 05.07.2017 Woods Hole, MA, US, United States of America Galliot Brigitte;
Paris REDOX World Congress 2017 Poster A complex epithelial-interstitial crosstalk via ROS signaling and injury-induced cell death drives head regeneration in Hydra 26.06.2017 Paris, France Suknovic Nenad;
Gordon Research Conference: Tissue Repair and Regeneration 2017 Talk given at a conference Regeneration and Resistance to Aging, Two Faces of the Same Coin in Hydra? 04.06.2017 New London, NH, US, United States of America Galliot Brigitte;
Seminars UCL Biosciences Individual talk Regeneration and Aging, Two Faces of the Same Coin? 23.03.2017 Londres, Great Britain and Northern Ireland Galliot Brigitte;
9th International PhD Program Conference 2017 Poster Injury-inudced ROS signaling in regenerating Hydra 18.01.2017 Montreux, Switzerland Suknovic Nenad;
Berlin-Brandenburg School for Regenerative Therapies 7th PhD Symposium 2016 Individual talk Regeneration and Aging, Two Faces of the Same Coin? 30.11.2016 Berlin, Germany Galliot Brigitte;
Master Program Mechanisms of Development 2016, Ecole Normale Supérieure de Lyon Individual talk Hydra a model system for regeneration and aging studies 09.11.2016 Lyon, France Galliot Brigitte;
5th iGE3 Annual Meeting 2016 - PhD salary award presentation - Talk given at a conference Translatin injury into regeneration: the role of Reactive Oxagen Species (ROS) 08.11.2016 Geneva, Switzerland Suknovic Nenad;


Communication with the public

Communication Title Media Place Year
Media relations: radio, television La tête au carré - Les secrets de la longévité - France Inter International 2019
Media relations: print media, online media Les secrets de la longévité - L’hydre, cette immortelle des étangs La Salamandre International Western Switzerland 2019
Media relations: print media, online media Mini-monsters with multiple heads created in the lab Live Science International 2019
Media relations: print media, online media Pourquoi les hydres n’ont finalement qu’une tête Communiqué de presse Unige Western Switzerland 2019
Media relations: radio, television Tendance jeûne RTS Western Switzerland 2019
Media relations: radio, television Entre nous soit dit - Brigitte Galliot - RTS Western Switzerland 2018
Media relations: radio, television CQFD Il reste de la vie après la mort RTS Western Switzerland 2017
Media relations: print media, online media Le Temps Brigitte Galliot et Denis Duboule: en constante évolution Western Switzerland 2017
Media relations: radio, television Rencontre avec Brigitte Galliot RTS Western Switzerland 2016

Awards

Title Year
iGE3 PhD Salary Awards 2016 (2 years of salary) 2016

Associated projects

Number Title Start Funding scheme
189122 Developmental and cellular mechanisms that underlie regeneration and slow aging in Hydra 01.11.2019 Project funding (Div. I-III)
149630 Regulation of stem cell plasticity in Hydra 01.10.2013 Project funding (Div. I-III)
183529 Multiphoton confocal microscope for multimodal tissue imaging and fluorescence lifetime measurements 01.02.2020 R'EQUIP

Abstract

The freshwater Hydra polyps provide a unique model system to investigate the mechanisms that maintain in an animal long-term homeostasis, injury-induced regeneration but also adaptation to harsh conditions such as prolonged starvation or elimination of neurogenesis. Over the recent years, our laboratory applied extensively quantitative RNA-seq transcriptomics to learn about gene regulations involved in (i) positional information, (ii) stem cells, (iii) epithelial plasticity, (iv) regeneration in Hydra vulgaris and (v) aging versus non-aging in two Hydra oligactis strains. All these data are going to be published in a Hydra gene expression atlas. Animals that lose interstitial stem cells (i-cells) and neurogenesis remain fit, able to regenerate and bud if force-fed on the long term. Thanks to the combinatorial analysis of various RNA-seq datasets, we could show that epithelial cells in Hydra vulgaris adapt to the loss of neurogenesis by overexpressing a large subset of genes, some of them exhibiting potential neurogenic or neurotransmission functions (Wenger et al. 2016). We now wish to test the functional role of candidate regulators of epithelial plasticity as TCTP2 in Hydra vulgaris and in mammalian cells. By contrast epithelial cells in the cold-sensitive strain of Hydra oligactis (Ho_CS) lack this property of adaptation, and as a consequence Ho_CS animals lose their fitness and the possibility to regenerate, they rapidly age and die upon loss of i-cells (Tomczyk et al. in preparation). Autophagy in aging Ho_CS is deficient, with the accumulation of the selective autophagy receptors p62/SQSTM and NBR1, which typically signs a blocked autophagy flux. We propose to investigate the mechanisms of aging in Ho_CS by investigating the role of p62/SQSTM in selective autophagy. In parallel we plan to investigate the mechanisms that allow an adult animal to reactivate a developmental program upon injury. In Hydra, this phenomenon is due to the immediate transformation of the gastric tissue into an organizer, a tissue that can instruct and recruit surrounding tissues to differentiate a new head on one side or a basal disc on the other. The cross-talk between the immediate ROS injury signals and the pre-injury homeostatic conditions likely provide positional cues that inform the tissue on what developmental program to reactivate. Deciphering this cross-talk is essential to understand how a tissue launches a certain regeneration program. Concerning the subsequent patterning, classical transplantation experiments have demonstrated that the apical organizer produces two substances, an activator and an inhibitor, both necessary to set up a unique, well-patterned head. According to the Gierer-Meinhardt model of de novo pattern formation, the activator acts locally and self-enhances its activity as demonstrated for HyWnt3. By contrast the molecular nature of the inhibitory cascade remains unknown although it is predicted to be produced under the control of the activator, highly diffusible and thus acting over long distance. Thanks to regenerative transcriptomics, we identified two candidates, a potential secreted signal and a transcription factor. We plan to test these candidates in functional assays in Hydra and zebrafish. This second part of the project will highlight the mechanisms that re-establish a complex 3D structure in an adult organism after amputation.
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