Edgar Gomes Lab

Arquitetura Celular

Ligar o núcleo ao citoesqueleto é relevante para vários processos celulares e as perturbações destas ligações resultam em várias patologias. O posicionamento nuclear dentro do citoplasma da célula requer uma conexão entre o núcleo e o citoesqueleto.

No nosso laboratorio estamos interessados em compreender os processos envolvidos nestas ligações e o papel do posicionamento do núcleo na função da célula.

No nosso laboratório estudamos a migração celular e formação de células musculares esqueléticas que exigem a ligação entre o núcleo e o citoesqueleto e o posicionamento preciso do núcleo. Usamos diferentes abordagens moleculares e celulares em  combinação com a análise em video para responder a estas perguntas.

Equipa de Investigação

Áreas de Investigação

• Mecanismos de movimento do núcleo durante a migração celular e formação de músculo esquelético
• Função do posicionamento do núcleo na formação do músculo esquelético

Projetos de Investigação em Curso

2019-2025 ERC Synergy. ArpComplexity: Defining the role of Arp2/3 complex diversity at multiple scales of biology. Coordenação: Edgar Gomes. Agência Financiadora: Comissão Europeia.

2018-2022 FETOPEN - MyoChip Project. MyoChip: Building a 3D innervated and irrigated muscle on a chip. Coordenação: Edgar Gomes. Agência Financiadora: Comissão Europeia.

2018-2021 Posicionamento do núcleo das células musculares esqueléticas. Coordenação: Edgar Gomes. Agência Financiadora: Fundação para a Ciência e a Tecnologia.

Projetos de Investigação Anteriores

2016-2019 Coordenação do Consórcio H2020-TWINN-2015 Cancer Biology

2016-2018 ERC proof of concept Grant

2014-2019 ERC Consolidator Grant

2014-2019 EMBO Installation Grant

2014-2019 Investigador FCT

Publicações Selecionadas

Calero-Cuenca FJ, Osorio DS, Carvalho-Marques S, Sridhara SC, Oliveira LM, Jiao Y, Diaz J, Janota CS, Cadot B, Gomes ER. Ctdnep1 and Eps8L2 regulate dorsal actin cables for nuclear positioning during cell migration. Curr Biol. (2021) Feb 9:S0960-9822(21)00040-3.

Roman, W., Pinheiro, H., Pimentel, M.R., Segalés, J., Oliveira, L.M., García-Domínguez, E., Gómez-Cabrera, M.C., Serrano, A.L., Gomes, E.R., and Muñoz-Cánoves, P. (2021). Muscle repair after physiological damage relies on nuclear migration for cellular reconstruction. Science 374, 355–359.

Pinheiro, H., Pimentel, M.R., Sequeira, C., Oliveira, L.M., Pezzarossa, A., Roman, W., and Gomes, E.R. (2021). mRNA distribution in skeletal muscle is associated with mRNA size. Journal of Cell Science 134.

Savulescu, A.F., Brackin, R., Bouilhol, E., Dartigues, B., Warrell, J.H., Pimentel, M.R., Beaume, N., Fortunato, I.C., Dallongeville, S., Boulle, M., et al. (2021). Interrogating RNA and protein spatial subcellular distribution in smFISH data with DypFISH. Cell Reports Methods

Gomes, Edgar R.; de Almeida, Sérgio F.. (2021) "TREX1-dependent DNA damage links nuclear rupture to tumor cell invasion". Developmental Cell 56 22 : 3040-3041.

Janota CS, Calero-Cuenca FJ, Gomes ER., (2020) Methods to Measure Perinuclear Actin Dynamics During Nuclear Movement in Migrating Cells. Methods in Molecular Biology (Clifton, N.J.)

Déjardin T, Carollo PS, Sipieter F, Davidson PM, Seiler C, Cuvelier D, Cadot B, Sykes C, Gomes ER, Borghi N (2020). Nesprins are mechanotransducers that discriminate epithelial-mesenchymal transition programs. Journal of Cell Biology 219(10):e201908036.

Roman W, Pimentel MR, Gomes ER, (2018) An In Vitro System to Measure the Positioning, Stiffness, and Rupture of the Nucleus in Skeletal Muscle. Methods in Molecular Biology (Clifton, N.J.)

Infante E, Castagnino A, Ferrari R, Monteiro P, Agüera-González S, Paul-Gilloteaux P, Domingues MJ, Maiuri P, Raab M, Shanahan CM, Baffet A, Piel M, Gomes ER, Chavrier P.LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration.  Nat Commun. 2018 Jun 22;9(1):2443. doi: 10.1038/s41467-018-04865-7

Roman W, Martins JP, Gomes ER. Local Arrangement of Fibronectin by Myofibroblasts Governs Peripheral Nuclear Positioning in Muscle Cells. Dev Cell. 2018 Jun 15. pii: S1534-5807(18)30430-1. doi: 10.1016/j.devcel.2018.05.031.

Calero-Cuenca FJ, Janota CS, Gomes ER. Dealing with the nucleus during cell migration. Curr Opin Cell Biol. 2018 Feb;50:35-41. doi: 10.1016/j.ceb.2018.01.014.

Roman W, Gomes ER. Nuclear positioning in skeletal muscle. Semin Cell Dev Biol. 2017 Dec 11. pii: S1084-9521(17)30428-7. doi: 10.1016/j.semcdb.2017.11.005.

Gimpel, P., Lee, Y.L., Sobota, R.M., Calvi, A., Koullourou, V., Patel, R., Mamchaoui, K., Nédélec, F., Shackleton, S., Schmoranzer, J., Burke, B., Cadot, B., Gomes, E. R.(2017) Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells. Current Biology. doi.org/10.1016/j.cub.2017.08.031

Roman, W., Martins, J., Carvalho, F. A., Voituriez, R., Abella, J. V. G., Santos, N. C., Cadot, B., Way, M., and Gomes, E. R.(2017) Myofibril contraction and crosslinking drive nuclear movement to the periphery of skeletal muscle. Nat. Cell Biol. 1189–1201 doi:10.1038/ncb3605

Cátia S. Janota, Francisco J. Calero-Cuenca, Judite Costa, Edgar R. Gomes (2017). SnapShot: Nucleo-cytoskeletal Interactions. Cell 2017; 169(5):970-970.e1.

Pimentel MR, Falcone S, Cadot B, Gomes ER. In Vitro Differentiation of Mature Myofibers for Live Imaging. J Vis Exp. 2017 Jan 7;(119). doi: 10.3791/55141.

Vilmont V, Cadot B, Vezin E, Le Grand F, Gomes ER. Dynein disruption perturbs post-synaptic components and contributes to impaired MuSK clustering at the NMJ: implication in ALS. Sci Rep. 2016 Jun 10;6:27804. doi: 10.1038/srep27804.

Vilmont V, Cadot B, Ouanounou G, Gomes ER. A system for studying mechanisms of neuromuscular junction development and maintenance. Development. 2016 Jul 1;143(13):2464-77. doi: 10.1242/dev.130278. Epub 2016 May 25.

D’Alessandro, M., Hnia, K., Gache, V., Koch, C., Gavriilidis, C., Rodriguez, D., Nicot, A.-S., Romero, N.B., Schwab, Y., Gomes, E.R., Labouesse, M., Laporte, J. (2015). Amphiphysin 2 Orchestrates Nucleus Positioning and Shape by Linking the Nuclear Envelope to the Actin and Microtubule Cytoskeleton.Developmental Cell 35, 186–198.

Cadot B, Gache V, Gomes ER. Moving and positioning the nucleus in skeletal muscle - one step at a time. Nucleus. 2015;6(5):373-81. doi: 10.1080/19491034.2015.1090073.

Sestina Falcone, William Roman, Karim Hnia, Vincent Gache, Nathalie Didier, Jeanne Lainé, Frederic Aurade, Isabelle Marty, Ichizo Nishino, Nicolas Charlet-Berguerand, Norma Romero, Giovanna Marazzi, David Sassoon, Jocelyn Laporte, Edgar R. Gomes. N-WASP is required for Amphiphysin-2/BIN1-dependent nuclear positioning and triad organization in skeletal muscle and is involved in the pathophysiology of centronuclear myopathy. EMBO Mol Med 6, 1455–1475 (2014) (PDF)

Cadot B, Gache V, Gomes ER. Fast, multi-dimensional and simultaneous kymograph-like particle dynamics (SkyPad) analysis. PLoS One. 2014 Feb 19;9(2):e89073. doi: 10.1371/journal.pone.0089073.

Osorio DS, Gomes ER. Connecting the nucleus to the cytoskeleton for nuclear positioning and cell migration. Adv Exp Med Biol. 2014;773:505-20. doi: 10.1007/978-1-4899-8032-8_23.

Osorio DS, Gomes ER. The contemporary nucleus: a trip down memory lane. Biol Cell. 2013 Sep;105(9):430-41. doi: 10.1111/boc.201300009.

Gache V, Cadot B, Gomes ER. [Spatial distribution of nuclei in muscle fibers: a novel actor of muscular function]. Med Sci (Paris). 2012 Jun-Jul;28(6-7):577-9. doi: 10.1051/medsci/2012286007.

Metzger, T., Gache, V., Xu, M., Cadot, B., Folker, E., Richardson, B., Gomes, E.R.*, Baylies, M.K.*. MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function. Nature 484, 120–124 (2012), *co-last and corresponding author

Cadot, B., Gache, V., Vazyutina, E., Falcone, S., Birchmeier, C., Gomes. E.R. Nuclear movement during myotube formation is microtubule and dynein dependent and is regulated by Cdc42, Par6 and Par3. EMBO Reports, 13(8):741-9 (2012)

Borrego-Pinto, J., Jegou, T., Osorio, D., Aurade, F., Gorjánácz, M., Koch, B., Mattaj, I., and Gomes, E. R. (2011). Samp1 is a component of TAN lines and is required for nuclear movement. Journal of Cell Science, 125, 1099–105 (2012)

Luxton GW, Gomes ER, Folker ES, Worman HJ, Gundersen GG. TAN lines: a novel nuclear envelope structure involved in nuclear positioning. Nucleus. 2011 May-Jun;2(3):173-81. doi: 10.1073/pnas.1000824108.

Luxton GW*, Gomes ER*, Folker ES, Vintinner E, Gundersen GG. Linear arrays of nuclear envelope proteins harness retrograde actin flow for nuclear movement. Science. 2010 Aug 20;329(5994):956-9.*co-first author

Mitchell KJ, Pannérec A, Cadot B, Parlakian A, Besson V, Gomes ER, Marazzi G, Sassoon DA. Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development. Nat Cell Biol. 2010 Mar;12(3):257-66. doi: 10.1038/ncb2025.

Mitchell KJ, Pannérec A, Cadot B, Parlakian A, Besson V, Gomes ER, Marazzi G, Sassoon DA. Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development. Nat Cell Biol. 2010 Mar;12(3):257-66. doi: 10.1038/ncb2025.

Ostlund C, Folker ES, Choi JC, Gomes ER, Gundersen GG, Worman HJ. Dynamics and molecular interactions of linker of nucleoskeleton and cytoskeleton (LINC) complex proteins. J Cell Sci. 2009 Nov 15;122(Pt 22):4099-108. doi: 10.1242/jcs.057075.

Gomes ER, Gundersen GG. Real-time centrosome reorientation during fibroblast migration. Methods Enzymol. 2006;406:579-92

E.R. Gomes, S. Jani, G.G. Gundersen. Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell, 2005, 121: 451-63

Evans KJ, Gomes ER, Reisenweber SM, Gundersen GG, Lauring BP. Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing. J Cell Biol. 2005 Feb 14;168(4):599-606.

Gundersen GG, Gomes ER, Wen Y. Cortical control of microtubule stability and polarization. Curr Opin Cell Biol. 2004 Feb;16(1):106-12

Dujardin DL, Barnhart LE, Stehman SA, Gomes ER, Gundersen GG, Vallee RB. A role for cytoplasmic dynein and LIS1 in directed cell movement. J Cell Biol. 2003 Dec 22;163(6):1205-11

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