Juan Manuel García Arcos

Juan Manuel Garcia Arcos

Juan Manuel García Arcos Etudiant en thèse Tél :

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Résumé grand public

 

Les cellules se déplacent dans le corps par exemple lorsqu’elles cherchent une infection pour nous guérir. Mais, dans certaines conditions, le déplacement des cellules est la cause d’une maladie. C’est le risque plus important pour les patients atteints de cancer. La métastase est la migration des cellules au-delà de la tumeur principale et provoque l’expansion du cancer. Les traitements contre la métastase parfois ne fonctionnent pas parce que les cellules peuvent utiliser différentes stratégies pour migrer à travers des tissus. Dans le type de migration amiboïde, les cellules se contractent et se glissent à travers des espaces entre les fibres des tissus. Ce type de migration est celui que nous comprenons le moins : nous ne savons pas comment les cellules arrivent à tirer des fibres ou comment elles arrivent à se guider parmi les fibres de la matrice extracellulaire. Le type de migration amiboïde est aussi le plus fréquent lors des cancers plus agressifs, et est favorisée quand les cellules sont déformées.

Dans ma thèse, j’étudie les blebs, qui sont les protrusions que les cellules amiboïdes utilisent pour migrer. D’abord associés à l'apoptose, les « blebs » sont identifiés comme des structures importantes pour la migration des cellules cancéreuses amiboïdes. Ces blebs se forment lorsque la membrane plasmique se détache de la cellule (comme une bulle). Les blebs se rétractent après leur formation, exerçant des forces de friction sur le substrat. De manière pratique, je comprime des cellules sur différents substrats (plats, avec des sillons…) et je fais des vidéos pour mieux comprendre comment les blebs se forment, se stabilisent, et guident les cellules amiboïdes. La réussite de mes recherches contribuera à trouver de nouvelles cibles thérapeutiques pour arrêter la migration amiboïde.

 

Research summary

Introduction

Metastasis is one of the leading causes of mortality in cancer patients (Hanahan et al. Cell 2011). Amoeboid single cell migration is associated with metastatic cancer and higher cell contractility. Previously associated with apoptosis, blebs have arisen in the past decade as important structures for amoeboid cell migration, particularly for cancer cells (Fackler et al. JCB 2008, Charras et al. Nat Rev Mol Cell Biol. 2008). Blebs are formed when the plasma membrane detaches from the actomyosin cortex. Then, the cytoplasm driven by intracellular pressure flows into the expanding bleb, until a new actomyosin cortex is reassembled beneath the membrane and contracts (Charras et al. JCB 2006). This exerts friction forces on the substrate and allows cells to migrate.

In recent years, a few independent studies have reported blebs which are large and stable in cells under non-adhesive confinement, creating a continuous actomyosin flow driving the entire cell (Bergert PNAS 2012, Ruprecht et al. Cell 2015, Liu et al. Cell 2015). Unlike previous blebs described, they are able to overcome retraction and stabilize a constant flow. Stable blebs are a new type of cellular structures that amoeboid cells use to migrate, analogous to filopodia or lamellipodia for mesenchymal cells. In a single cancer cell under non-adhesive confinement, multiple blebs are formed and compete against each other, so that eventually a single bleb drives the migration. Thus, it is important to know how single blebs are stabilized to understand how single-bleb amoeboid cells polarize.

Objectives and hypotheses

During my Ph.D. I study bleb morphogenesis and bleb stabilization in confined cancer cells. The first part of my project describes the blebs forming as an immediate response of cells to confinement. Charras et al. JCB 2006 was the first study to look closely on the process of cortex formation in blebs, identifying ERM proteins and Eps8 (actin bundling/capping protein) upstream of actin recruitment. More recent studies confirmed the presence of components of the actin polymerizing proteins arp2/3 complex, WAVE complex, formin mDia1, and cortactin in blebs. However, no study has shown so far the morphogenesis of a stable bleb. My goal is to demonstrate that spatiotemporal localization of cytoskeletal components controls bleb stability

The second part of my project focuses on other mechanisms promoting stabilization. Recent reports highlighted the importance of actin bundling by Eps8 for polarization of unique-bleb amoeboid cells (Logue et al. eLife 2015). Nanotopography can interfere with actin arrangement in the cortex and promote directional migration in amoeba (Driscoll et al. ACS Nano 2014). I hypothesize that bundling and cortex arrangement promoted by external physical cues such could collaborate with Eps8 in arranging the actin cortex for bleb stabilization. We hypothesize that bleb stabilization depends on actin filament arrangement at the bleb tip. In order to check that, I modify the physical environment of cells and study the morphodynamics of blebs. I complete this work with advanced imaging of single actin filaments and tagged cytoskeleton-associated molecules at the bleb tip under the effect of a range of inhibitors.

 

Academic CV

Current situation

PhD student. Laboratoire : Institut Pierre Gilles de Gennes / Institut Curie, CNRS, UMR144, Paris. Université : école doctorale 474 « Frontières du vivant ». Centre de Recherches Interdisciplinaires, Université Paris Descartes.

Project: Mécanismes de stabilisation et motilité des blebs dans les cellules cancéreuses

Funding: ITMO Cancer, Alliance pour les Sciences de la Vie et de la Santé, AVIESAN.

Supervisor: Dr. Matthieu Piel                  Co-supervisor: Dr. Damien Cuvelier

Team: System cell biology of cell polarity and cell division.

Education

2015 - 2016        Master “EdTech” (education) at Center for Research and Interdisciplinarity and Paris Descartes University (France). 60 ECTS. Supported by La Caixa Europa post-graduate fellowship.

2014 - 2015        Master  “Approches Interdisciplinaires du Vivant” (interdisciplinary life sciences / quantitative biology) at Center for Research and Interdisciplinarity and Paris Diderot University (France). 60 ECTS. Supported by MIEM fellowship.

2010 - 2014        Biotechnology degree (4 years, 240 ECTS) at Pablo de Olavide University (Spain). Supported by general scholarship from the Ministry of Education (Spain).

Entrepreneurship

Founder and president of Open Science School (2014-present). NGO based in Paris, France, dedicated to teach life sciences to non-professional scientists (designers, architects, …), foster interdisciplinary collaboration, and help high school science teachers creating new content and lab protocols.

Founder of and director (2016-2018) of Unibiome, start-up based in Paris on food probiotecs. Incubated and got an investment of 60K€ from IndieBio EU.

Founder and director of Open Science Tools (2016-2017). Start-up based in Shenzhen, China, dedicated to open source science hardware and science teaching to schools.

Research experience

2016                     Research student at Tsinghua Graduate School at Shenzhen, China. Open F.I.E.S.T.A. institute. Project: Development of a practice-based science program in Mingde middle school in Shenzhen (China).

2015                     Research staff at PILI SAS and IndieBio (Paris, France and Cork, Ireland). Jun-Aug 2015. Project: Synthetic biology in Streptomyces spp. and a collaborative project between design and sciences for textile dyeing with bacteria-produced colorants.

2015                     Research staff at University College London (UK). Jan-Apr 2015. Project: Live cell imaging in Sulfolobus spp. Unraveling the evolutionary Archaeal origins of cell complexity.

2014                     Associate Research staff at Institut Curie (France). December 2014.

2014                     iGEM Paris-Bettencourt team (France). From Jul 2013. Project: Community manager, education tools for High Schools. Isolation of natural mutants in skin microbiome samples. http://2014.igem.org/Team:Paris_Bettencourt

2013 - 2014        Erasmus+ working program at Institut Curie (France). Sept 2013 - Jul 2014. Project: Study of the mitochondrial network throughout mitosis and interphase in patterned RPE1 cells.

2013                     Erasmus exchange at École de Biologie Industrielle (France). Feb 2013 - Jun 2013. Project: Design, production and purification of human fibronectin fragments in E. coli. Optimization and production at a medium-scale level.

2012 - 2013        Internship in Molecular Biology and Genetics. Centro Andaluz de Biología del Desarrollo (CABD). Jul 2013 and Dec 2012 – Feb 2013. Project: Identification of molecular targets for the detoxification of cytotoxic compounds in S.pombe.

2012                     Student exchange at NMSU (USA). Internship in the Chili Pepper Institute. Aug-Dec 2012. Project: Identification of molecular differences between chili pepper cultivar "Costeño Amarillo" individuals.

Academic publications

Reconstitution of cell migration at a glance (2019). Journal of Cell Science. Juan Manuel Garcia-Arcos, Renaud Chabrier, Mathieu Deygas, Guilherme Nader, Lucie Barbier, Pablo Jose Saez, Aastha Mathur, Pablo Vargas, and Matthieu Piel. (in press)

Correlations of carotenoid content and transcript abundances for fibrillin and carotenogenic enzymes in Capsicum annuum fruit (2015). Plant Science. James Kilcrease, Laura Rodriguez-Uribe, Richard D Richins, Juan Manuel Garcia Arcos, Jesus Victorino, Mary A O'Connell.

Other employement and science outreach activties

2015 - present   President, Founder of Open Science School association (Paris, France). Since April 2015. Project: Teaching science and interdisciplinarity to high schoolers through synthetic biology. In collaboration with Center for Research and Interdisciplinarity, the Académie de Versailles and Savanturiers. Grants received from University of Cambridge, University College London (Institute of Making), TsingHua University (Open FIESTA graduate School at Shenzhen) and Université Paris Descartes (CRI Paris). openscienceschool.org

2017                     Organization of a microfluidics weekend workshop at Espace Pierre Gilles de Gennesand Institut Pierre-Gilles de Gennes in ESPCI (Paris). Participation in “La nuit de la Science 2017”.

2016 - 2018        Consultant for scientific program development in Chinese schools. SDGO (sdgo.ooo).

2016 - 2017        Mission doctorale de diffusion scientifique with the EU program Doing It Together Science (grant H2020 no. 709443) Project: practical science workshops in high schools related to biodesign and biotech.

2015                     Art exhibition in University College London Art Society.

2012 - 2015       Member of the board of directors the Association of Biotechnologists of Andalusia (ASBAN).

2014                     Candidate in a national list (Spain) for the European Parliament elections 2014. http://juanmagar.wix.com/candidatura

2011                     Art exhibition in the city hall of Chipiona (Spain).

Language skills

Spanish: Native. English: Currently proficient. Score 110/120 at TOEFL iBT (Feb 2015). French: Currently proficient. B2 certification (2012).

Awards and scholarships

Short-Term EMBO fellowship no. 7873 (September - December 2018) in the lab of Dr. Stephan Wieser in the Institute of Photonic Sciences (ICFO) in Castelldefels (Spain). Project: High NA TIRF/SIM microscopy of amoeboid bleb migration.

Travel grant (2018) Gathering for Open Science Hardware in Shenzhen (China).

Travel grant (2017) Gathering for Open Science Hardware in Santiago (Chile).

Gold medal (2015) at IGEM (international genetically engineered machine) student competition in Hynes Convention Center. Boston, Massachusetts.

La Caixa fellow (2015) full scholarship for graduate studies.

MIEM Paris Sorbonne Universités fellow (2014) full scholarship for master’s program.

Best poster prize (2014) at biotech Annual Congress of the Spanish Federation of Biotechnologists, Barcelona.

Best supporting art and design, Best New Application, and Gold Medal at 2014 IGEM (international genetically engineered machine) student competition in Hynes Convention Center. Boston, Massachusetts.

Scholarship for undergraduate tuition fees. Ministry of Education (Spain).

Teaching experience

2018                     Synthetic Biology course teaching assistant in Master AIV program, Center for Research and Interdiciplinarity (Paris). Science workshop in high school Antonio Dominguez Ortiz in Sevilla (Spain).

2017                     Experimental design and microfluidics course in FdV undergraduate program, Center for Research and Interdiciplinarity (Paris). Science workshop in high schools belonging to Academie de Versailles.

2016                     Biodesign workshop for master’s students in Open FIESTA Master’s Program. Shenzhen (China).

2015                     Biodesign workshop for master’s students in Open FIESTA Master’s Program. Shenzhen (China).

2012                     Semana de la Ciencia in the university Pablo de Olavide (Spain).

Scientific courses

2018                     Cell Biology course. Fundacion Ciencia y Vida, Santiago (Chile).

2018                     NEUBIAS Image Analysis course. Szeged Institute of computational sciences (Hungary).

2017                     Cytoskeleton course. Institut Curie, Paris (France).