{"id":1307,"date":"2024-07-31T14:29:45","date_gmt":"2024-07-31T14:29:45","guid":{"rendered":"https:\/\/gimm.pt\/our-work\/laboratories\/laboratorio-sergio-de-almeida\/"},"modified":"2026-05-06T14:50:55","modified_gmt":"2026-05-06T14:50:55","slug":"laboratorio-sergio-de-almeida","status":"publish","type":"lab","link":"https:\/\/gimm.pt\/pt-pt\/o-nosso-trabalho\/laboratorios\/laboratorio-sergio-de-almeida\/","title":{"rendered":"Laborat\u00f3rio S\u00e9rgio de Almeida"},"content":{"rendered":"\n<h3 class=\"wp-block-heading\">Cromatina e Epigen\u00e9tica<\/h3>\n\n\n\n<p><\/p>\n\n\n\n<p>A nossa investiga\u00e7\u00e3o centra-se nos mecanismos que controlam a din\u00e2mica da cromatina durante a transcri\u00e7\u00e3o e a repara\u00e7\u00e3o de danos no ADN e na forma como estes se coordenam com os processos que salvaguardam a integridade do genoma. Os nossos objectivos gerais s\u00e3o dois: em primeiro lugar, pretendemos investigar os aspectos moleculares das diferentes fases do ciclo de transcri\u00e7\u00e3o, centrando-nos no processamento do pr\u00e9-mRNA e nos eventos de modifica\u00e7\u00e3o da cromatina; al\u00e9m disso, estudamos os mecanismos moleculares que detectam, sinalizam e reparam os danos no ADN. Em paralelo, estamos interessados em explorar de que forma as classes abundantes de elementos transpon\u00edveis contribuem para a fun\u00e7\u00e3o e a estabilidade do genoma nos genomas dos mam\u00edferos, recorrendo a abordagens funcionais e bioinform\u00e1ticas.<\/p>\n\n\n\n<p>Para o efeito, utilizamos uma estrat\u00e9gia de investiga\u00e7\u00e3o multidisciplinar que combina ferramentas experimentais e abordagens de \u00e1reas como a biologia celular e molecular, a bioqu\u00edmica, a microscopia de c\u00e9lulas vivas, a sequencia\u00e7\u00e3o de nova gera\u00e7\u00e3o e a bioinform\u00e1tica. Um dos principais objectivos da nossa investiga\u00e7\u00e3o \u00e9 compreender de que forma as altera\u00e7\u00f5es na transcri\u00e7\u00e3o, no processamento do pr\u00e9-mRNA, na modifica\u00e7\u00e3o da cromatina e na resposta aos danos no ADN est\u00e3o ligadas ao desenvolvimento de doen\u00e7as humanas como o cancro.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n<div style=\"position: relative;\" id=\"\" class=\"alignfull\">\n\n\t\n\t\n\t<div style=\"background-color: unset;\" class=\"wrapper_section  \">\n\n\t\t<section >\n\t\t\t<div class=\"container\">\n\n\n\t\t\t\t\t\t\t\t<div class=\"acf-innerblocks-container\">\n<div id=\"\" class=\"wp-block-gimm-partner-list\">\n\t<div class=\"row\">\n\t\t<div class=\"col-lg-12 wow fadeIn\">\n\t\t\t<h3 class=\"gimm_title pt-4 mb-2 wow fadeIn\">Funders<\/h3>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<div class=\"owl-carousel owl-theme owl-loaded owl-drag\">\n\t\t\t\t\t\t\t<div class=\"owl-stage-outer\">\n\t\t\t\t\t\t\t\t<div class=\"owl-stage\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<div class=\"owl-item \">\n\t\t\t\t\t\t\t\t\t\t\t<div class=\"item text-center\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" style=\"max-height:150px; object-fit: contain;\" class=\"img-fluid\" src=\"https:\/\/gimm.pt\/wp-content\/uploads\/2025\/03\/TessellateBio-logo-.png\"\n\t\t\t\t\t\t\t\t\t\t\t\t\t\talt=\"Tessellate Bio BV\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"owl-nav disabled\"><button type=\"button\" role=\"presentation\" class=\"owl-prev\"><span aria-label=\"Previous\">\u2039<\/span><\/button><button type=\"button\" role=\"presentation\"\n\t\t\t\t\t\t\t\t\tclass=\"owl-next\"><span aria-label=\"Next\">\u203a<\/span><\/button><\/div>\n\t\t\t\t\t\t\t<div class=\"owl-dots disabled\"><button role=\"button\" class=\"owl-dot active\"><span><\/span><\/button><\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/section>\n\t<\/div>\n\n<\/div>\n\n<div style=\"position: relative;\" id=\"\" class=\"alignfull\">\n\n\t\n\t\n\t<div style=\"background-color: unset;\" class=\"wrapper_section divider  \">\n\n\t\t<section >\n\t\t\t<div class=\"container\">\n\n\n\t\t\t\t\t\t\t\t<div class=\"acf-innerblocks-container\">\n<div id=\"\" class=\"wp-block-gimm-accordion\">\n\n\t<div class=\"accordion\" id=\"accordion\">\n\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-areas-de-investigacao\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#areas-de-investigacao\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"areas-de-investigacao\">\n\t\t\t\t\t\t\t<h3>\u00c1reas de Investiga\u00e7\u00e3o<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"areas-de-investigacao\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<h2>Resposta ao Dano no DNA e Repara\u00e7\u00e3o<\/h2>\n<p style=\"font-weight: 400\">Investigamos os mecanismos celulares que detetam, sinalizam e reparam o dano no DNA para manter a estabilidade do genoma. O nosso foco inclui as vias de repara\u00e7\u00e3o de roturas de cadeia dupla do DNA, como a recombina\u00e7\u00e3o hom\u00f3loga e a jun\u00e7\u00e3o de extremidades n\u00e3o hom\u00f3logas. Exploramos o papel da estrutura e din\u00e2mica da cromatina na coordena\u00e7\u00e3o do processo de repara\u00e7\u00e3o e o seu envolvimento na preven\u00e7\u00e3o da instabilidade gen\u00f3mica.<\/p>\n<p>&nbsp;<\/p>\n<h2>R-loops e Instabilidade Gen\u00f3mica Associada \u00e0 Transcri\u00e7\u00e3o<\/h2>\n<p style=\"font-weight: 400\">Estudamos como os R-loops, estruturas h\u00edbridas de RNA-DNA que se formam durante a transcri\u00e7\u00e3o, contribuem para a instabilidade gen\u00f3mica. A nossa investiga\u00e7\u00e3o centra-se na compreens\u00e3o dos mecanismos envolvidos na regula\u00e7\u00e3o dos R-loops e na forma como a sua desregula\u00e7\u00e3o conduz a danos no DNA associados \u00e0 transcri\u00e7\u00e3o. Pretendemos descobrir as vias moleculares que as c\u00e9lulas utilizam para resolver a instabilidade gen\u00f3mica induzida por R-loops.<\/p>\n<p>&nbsp;<\/p>\n<h2>Regula\u00e7\u00e3o da Transcri\u00e7\u00e3o e Processamento do Pr\u00e9-mRNA<\/h2>\n<p style=\"font-weight: 400\">Exploramos como o ciclo de transcri\u00e7\u00e3o est\u00e1 estreitamente acoplado a eventos de processamento do pr\u00e9-mRNA, como o splicing. Atrav\u00e9s do estudo de mecanismos regulat\u00f3rios chave do splicing, pretendemos compreender de que forma os defeitos na transcri\u00e7\u00e3o e no processamento do mRNA contribuem para o stress transcricional e a instabilidade gen\u00f3mica.<\/p>\n<p>&nbsp;<\/p>\n<h2>Instabilidade Gen\u00f3mica no Cancro<\/h2>\n<p style=\"font-weight: 400\">Investigamos como a instabilidade gen\u00f3mica impulsiona a progress\u00e3o do cancro, com foco em muta\u00e7\u00f5es em genes de repara\u00e7\u00e3o do DNA e reguladores da cromatina. O nosso trabalho visa revelar como os defeitos na resposta ao dano no DNA, aliados ao stress de transcri\u00e7\u00e3o e replica\u00e7\u00e3o, contribuem para a tumorig\u00e9nese. Adicionalmente, exploramos o potencial de direcionar terapias anticancer\u00edgenas para a instabilidade gen\u00f3mica, explorando vulnerabilidades nas vias de repara\u00e7\u00e3o do DNA das c\u00e9lulas cancerosas.<\/p>\n<p>&nbsp;<\/p>\n<h2>Elementos Transpon\u00edveis e Fun\u00e7\u00e3o do Genoma<\/h2>\n<p style=\"font-weight: 400\">Pretendemos compreender como os elementos transpon\u00edveis, em particular os da fam\u00edlia LINE-1, evolu\u00edram para regular o desenvolvimento dos mam\u00edferos e como a sua desregula\u00e7\u00e3o pode contribuir para o envelhecimento e para o estabelecimento e progress\u00e3o de contextos patol\u00f3gicos, em particular perturba\u00e7\u00f5es neurol\u00f3gicas como a s\u00edndrome de Rett. Para tal, combinamos modelos de c\u00e9lulas estaminais e seus derivados diferenciados com abordagens baseadas em CRISPR-Cas9 e tecnologias de sequenciamento de nova gera\u00e7\u00e3o.<\/p>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-projetos\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#projetos\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"projetos\">\n\t\t\t\t\t\t\t<h3>Projetos<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"projetos\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p><strong>2025-2027:<\/strong> Unveiling the DNA Damage Response in Skeletal Muscle Resilience and Repair. Coordena\u00e7\u00e3o: S\u00e9rgio de Almeida. Ag\u00eancia Financiadora: AFM-Telethon.<\/p>\n<p><strong>2025-2026:<\/strong> AIR-LOOP &#8211; Innovative strategies for targeting hidden weaknesses in cancer cells. Cordena\u00e7\u00e3o: Robert Martin &amp; S\u00e9rgio de Almeida. Funding Agency: &#8220;la Caixa&#8221; Foundation &#8211; Impulse Health Innovation.<\/p>\n<p><strong>2025-2027:<\/strong> CRISPR-based genome-wide screens for new regulators of LINE-1 elements activity. Coordena\u00e7\u00e3o: Anne-Valerie Gendrel. Funding Agency: Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia.<\/p>\n<p><strong>2024-2027:<\/strong> BIOMICS: Fostering Excellent Research, Training and Innovation in Biomedical Data Science. Parceiros: S\u00e9rgio de Almeida &amp; Anne-Valerie Gendrel. Ag\u00eancia Financiadora: EU twinning initiative (Horizon Europe).<\/p>\n<p><strong>2024:<\/strong> TessellateBio. Coordena\u00e7\u00e3o: S\u00e9rgio de Almeida. Ag\u00eancia Financiadora: Tessellate Bio BV.<\/p>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-projetos-anteriores\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#projetos-anteriores\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"projetos-anteriores\">\n\t\t\t\t\t\t\t<h3>Projetos Anteriores<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"projetos-anteriores\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p><strong>2023-2024:<\/strong> New horizons for Rett syndrome: exploring the role of transposable elements using genetically engineered human stem cell models. Coordena\u00e7\u00e3o: Anne-Valerie Gendrel. Ag\u00eancia Financiadora: Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia.<\/p>\n<p><strong>2023-2024:<\/strong> Investigating R-loops as important regulators of splicing. Coordena\u00e7\u00e3o: Robert Manfred Martin. Ag\u00eancia Financiadora: Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia.<\/p>\n<p><strong>2021-2024:<\/strong> O Papel da Transcri\u00e7\u00e3o Induzida por Quebras do DNA no Envelhecimento\u00a0\u00a0 &#8211; Decoding the Role of DNA Break-Induced Transcription in Ageing. Coordena\u00e7\u00e3o: S\u00e9rgio de Almeida. Ag\u00eancia Financiadora: Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia.<\/p>\n<p><strong>2021-2023:<\/strong> Exploring the contribution of transposable elements for the pathogenesis of Rett syndrome. Coordena\u00e7\u00e3o: Anne-Valerie Gendrel. Ag\u00eancia Financiadora: International Rett Syndrome Foundation.<\/p>\n<p><strong>2019-2022:<\/strong> Ribomed: RNA in Disease. Parceiro: S\u00e9rgio de Almeida. Ag\u00eancia Financiadora: EU twinning initiative (Horizon 2020).<\/p>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-publicacoes-selecionadas\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#publicacoes-selecionadas\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"publicacoes-selecionadas\">\n\t\t\t\t\t\t\t<h3>Publica\u00e7\u00f5es Selecionadas<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"publicacoes-selecionadas\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p>Gendrel, A.-V. (2025). The LINE\u20101 paradox: Active yet immobile. BioEssays, 47(2):e2400256. <a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bies.202400256\">https:\/\/doi\/10.1002\/bies.202400256<\/a>.<\/p>\n<p>Le Breton, A., Bettencourt, M. P., and Gendrel, A.-V. (2024) Navigating the brain and aging: exploring the impact of transposable elements from health to disease. Front Cell Dev Biol, 12:1357576. https:\/\/<a href=\"https:\/\/www.frontiersin.org\/journals\/cell-and-developmental-biology\/articles\/10.3389\/fcell.2024.1357576\/full\">doi\/10.3389\/fcell.2024.1357576<\/a>.<\/p>\n<p data-start=\"0\" data-end=\"230\">R.M. Martin, M.R. de Almeida, E. Gameiro, S.F. de Almeida (2023). Live-cell imaging unveils distinct R-loop populations with heterogeneous dynamics. <em data-start=\"149\" data-end=\"173\">Nucleic Acids Research<\/em>, Oct 11: gkad812. <a href=\"https:\/\/doi.org\/10.1093\/nar\/gkad812\" target=\"_new\" rel=\"noopener\" data-start=\"192\" data-end=\"227\">https:\/\/doi.org\/10.1093\/nar\/gkad812<\/a>.<\/p>\n<p data-start=\"232\" data-end=\"503\">J.C. Sabino, M.R. de Almeida, P.L. Abreu, A.M. Ferreira, M.M. Domingues, N.C. Santos, C.M. Azzalin, A.R. Grosso, S.F. de Almeida (2022). Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops. <em data-start=\"445\" data-end=\"452\">eLife<\/em> 11: e69476. <a href=\"https:\/\/doi.org\/10.7554\/eLife.69476\" target=\"_new\" rel=\"noopener\" data-start=\"465\" data-end=\"500\">https:\/\/doi.org\/10.7554\/eLife.69476<\/a>.<\/p>\n<p data-start=\"505\" data-end=\"701\">E.R. Gomes, S.F. de Almeida (2021). TREX1-dependent DNA damage links nuclear rupture to tumor cell invasion. <em data-start=\"614\" data-end=\"634\">Developmental Cell<\/em> 56(22): 3040-3041. <a href=\"https:\/\/doi.org\/10.1016\/j.devcel.2021.11.003\">https:\/\/doi.org\/10.1016\/j.devcel.2021.11.003<\/a>.<\/p>\n<p data-start=\"703\" data-end=\"945\">A.C. V\u00edtor, S.C. Sridhara, J.C. Sabino, A.I. Afonso, A.R. Grosso, R.M. Martin, S.F. de Almeida (2019). Single-molecule imaging of transcription at damaged chromatin. <em data-start=\"869\" data-end=\"887\">Science Advances<\/em> 5(1): eaau1249. <a href=\"https:\/\/doi.org\/10.1126\/sciadv.aau1249\" target=\"_new\" rel=\"noopener\" data-start=\"904\" data-end=\"942\">https:\/\/doi.org\/10.1126\/sciadv.aau1249<\/a>.<\/p>\n<p data-start=\"947\" data-end=\"1223\">S.C. Sridhara, S. Carvalho, A.R. Grosso, L.M. Gallego-Paez, M. Carmo-Fonseca, S.F. de Almeida (2017). Transcription dynamics prevent RNA-mediated genomic instability through SRPK2-dependent DDX23 phosphorylation. <em data-start=\"1160\" data-end=\"1174\">Cell Reports<\/em>. <a href=\"https:\/\/doi.org\/10.1016\/j.celrep.2016.12.050\" target=\"_new\" rel=\"noopener\" data-start=\"1176\" data-end=\"1220\">https:\/\/doi.org\/10.1016\/j.celrep.2016.12.050<\/a>.<\/p>\n<p data-start=\"1225\" data-end=\"1531\">A.R. Grosso, A.P. Leite, S. Carvalho, M.R. Matos, F.B. Martins, A.C. V\u00edtor, J.M. Desterro, M. Carmo-Fonseca, S.F. de Almeida (2015). Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma. <em data-start=\"1474\" data-end=\"1481\">eLife<\/em> 4: e09214. <a href=\"https:\/\/doi.org\/10.7554\/eLife.09214\" target=\"_new\" rel=\"noopener\" data-start=\"1493\" data-end=\"1528\">https:\/\/doi.org\/10.7554\/eLife.09214<\/a>.<\/p>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-premios\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#premios\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"premios\">\n\t\t\t\t\t\t\t<h3>Pr\u00e9mios<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"premios\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p style=\"font-weight: 400\"><strong>2015:<\/strong>Pr\u00e9mio da Sociedade Portuguesa de Gen\u00e9tica Humana<\/p>\n<p style=\"font-weight: 400\"><strong>2011:<\/strong> Pr\u00e9mio Pfizer Award de Investiga\u00e7\u00e3o B\u00e1sica<\/p>\n<p style=\"font-weight: 400\"><strong>2006:<\/strong> Pr\u00e9mio LabMed Science<\/p>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\n<\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/section>\n\t<\/div>\n\n<\/div>","protected":false},"featured_media":0,"template":"","acf":{"header_image":false,"ongoing_projects":"","selected_publications":"","useful_links":"","awards":"","funding":"","sponsorship":"","extra_information":false,"location":"Lisboa","subtitle":"Cromatina e Epigen\u00e9tica","team_leader":[{"ID":8278,"post_author":"1004","post_date":"2025-05-27 13:43:01","post_date_gmt":"2025-05-27 13:43:01","post_content":"","post_title":"S\u00e9rgio de 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