{"id":169,"date":"2022-09-08T09:32:48","date_gmt":"2022-09-08T08:32:48","guid":{"rendered":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_group&p=169"},"modified":"2022-12-21T10:19:38","modified_gmt":"2022-12-21T10:19:38","slug":"ferreira-group","status":"publish","type":"research_group","link":"https:\/\/biology.st-andrews.ac.uk\/research\/research-group\/ferreira-group\/","title":{"rendered":"Ferreira Group"},"content":{"rendered":"

The lab studies chromatin structure and dynamics. Chromatin influences all processes requiring access to the genome. Therefore factors that influence chromatin structure have far-reaching implications for normal development as well as carcinogenesis and disease. We use simple model organisms such as budding yeast\u00a0<\/span>(S. cerevisiae)<\/em>\u00a0<\/span>and nematodes (C. elegans)<\/em>\u00a0<\/span>to study how ATP-dependent chromatin remodelling enzymes alter chromatin, from local structure to global nuclear organisation, particularly of telomeres.<\/p>\n

Our aim is to gain mechanistic insight into chromatin remodelling enzymes relevant to human health \u2013 to promote the generation of new translational therapies.<\/strong><\/p>\n

Please visit our main lab website: https:\/\/ferreira.wp.st-andrews.ac.uk\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Our aim is to gain mechanistic insight into chromatin remodelling enzymes relevant to human health \u2013 to promote the generation of new translational therapies.<\/p>\n","protected":false},"author":70,"featured_media":170,"parent":0,"menu_order":0,"template":"","class_list":["post-169","research_group","type-research_group","status-publish","has-post-thumbnail","hentry"],"jetpack_sharing_enabled":true,"group_members":"

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People<\/h1>\r\n<\/header>\r\n
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Dr Helder Ferreira<\/a><\/strong><\/h3>\r\n
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\r\n\r\nI graduated with a B.Sc. Honours degree from Imperial College London and spent a year working in GlaxoWellcome before obtaining a PhD from the University of Dundee with\u00a0Prof. Tom Owen-Hughes<\/a>. I then did a postdoc in Switzerland at the Friedrich Miescher Institute with\u00a0Prof. Susan Gasser<\/a>\u00a0before joining the School of Biology as a lecturer in 2013.\r\n\r\n<\/div>\r\n<\/div>\r\n
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\r\n\r\nOur research focusses on chromatin dynamics from local chromatin structure to global nuclear organization and how this regulates cellular processes. In particular, I am interested in ATP-dependent chromatin remodelling enzymes and telomere maintenance. My goal is to understand how the cross-talk between these systems is regulated within a developmental context and to uncover novel targets of chromatin remodelling enzymes. This is done by combining forward genetic analysis in budding yeast and\u00a0C. elegans<\/em>\u00a0with biochemistry to obtain mechanistic insight into novel chromatin remodelling enzymes and the means by which they affect telomere function.\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n
\r\n\r\nDr Helder Ferreira\r\nBiomolecular Sciences Building\r\nUniversity of St Andrews\r\nNorth Haugh\r\nSt Andrews\r\nKY16 9ST\r\nFife\r\nUK\r\n\r\ntel: 01334 463425\r\nfax: 01334 462495\r\nroom: B303\r\nemail:\u00a0hcf2@st-andrews.ac.uk<\/a>\r\n\r\n<\/div>\r\n<\/div>\r\n\r\n
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Karim Hussain<\/strong><\/h4>\r\n<\/div>\r\n
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Dr Katerina Zabrady<\/strong><\/h4>\r\n<\/div>\r\n
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Amy Swanston<\/strong><\/h4>\r\n<\/div>\r\n<\/div>\r\n<\/div>","publications":"[publications flag='individual' code='hcf2' dois='1' max='10' categorise='1']","research_projects":"

Our research interests<\/h1>\r\nI have previously studied how specialised chromatin domains, namely telomeres, are spatially organised within the nucleus by sumoylation. Current projects involve studying the role of chromatin remodelling enzymes in genome stability and their interplay with telomeres.\r\n

Previous research projects<\/strong><\/b><\/h2>\r\nSUMO regulates telomere localisation in\u00a0<\/span>S. cerevisiae<\/em><\/i><\/strong><\/b>\r\n\r\nSUMO (Small\u00a0<\/span>Ubiquitin-like\u00a0<\/span>modifier) is a post-translational modification added onto lysine residues and has been linked to genome stability processes. We observed that deletion of the PIAS-like SUMO E3 ligase\u00a0<\/span>SIZ2<\/em><\/i>, but not other E3 ligases, led to telomere delocalisation from the nuclear periphery. We showed that Siz2 promotes both telomere anchoring pathways of budding yeast (Sir4 and Yku70\/80) and sumoylates these proteins\u00a0<\/span>in vivo<\/em><\/i>. Importantly, we showed that the defect in Yku70 and Yku80-4 mediated chromatin anchoring in\u00a0<\/span>siz2\u0394<\/em><\/i>\u00a0<\/span>cells can be overcome by making a linear fusion of Yku70 or Yku80 to SUMO. Deletion of\u00a0<\/span>SIZ2<\/em><\/i>\u00a0<\/span>also resulted in a telomerase-dependent increase in telomere length. Remarkably, the localisation and length phenotypes seen in\u00a0<\/span>siz2\u0394<\/em><\/i>\u00a0<\/span>cells appear to be functionally linked. We found that critically short telomeres detach from the nuclear periphery when they are most efficiently elongated. Our study was the first to show an effect of sumoylation on telomere anchoring and argues that Siz2-mediated control of telomere position helps regulate stable telomere maintenance.Figure 1. Model of Siz2 mediated effects on telomere localisation and elongation (Ferreira\u00a0<\/span>et al<\/em><\/i>\u00a0<\/span>NCB 2011)\r\n\r\nCharacterising\u00a0<\/span>C. elegans<\/em><\/i>\u00a0<\/span>telomere localisation<\/strong><\/b>\r\n\r\nWe have extended our work in yeast by looking at telomere localisation within the multicellular animal,\u00a0<\/span>C. elegans<\/em><\/i>. Using a telomere FISH protocol that we optimised (Figure 2), we find that\u00a0<\/span>C. elegans<\/em><\/i>\u00a0<\/span>telomeres are preferentially bound to the nuclear periphery. This perinuclear association increases during embryogenesis and persists in later larval stages. Remarkably, we find that, as in yeast, PIAS-mediated sumoylation is required for telomere anchoring in\u00a0<\/span>C. elegans<\/em><\/i>, being dependent on the SUMO E3 ligase GEI-17. We show that telomere position is independent of the Ku complex and of H3 K9 methylation but instead is dependent on the shelterin component POT-1 anchoring at nuclear envelope to SUN-1. To our knowledge, this is the first characterisation of telomere localisation and anchoring in\u00a0<\/span>C. elegans.<\/em><\/i>Figure 2. Telomere (red) and DNA (grey) staining of pachytene cells within the\u00a0<\/span>C. elegans<\/em><\/i>\u00a0<\/span>germline (Ferreira\u00a0<\/span>et al<\/em><\/i>\u00a0<\/span>JCB 2013).\r\n

Ongoing\u00a0<\/span>research projects<\/strong><\/b><\/h2>\r\nChromatin remodelling and genome stability<\/strong><\/b>\r\n\r\nATP-dependent chromatin remodeling enzymes (Snf2-family ATPases) are a large class of motor proteins that have increasingly been shown to be important for DNA repair. Additionally, mutations in a number of Snf2 proteins lead to various developmental disorders as well as carcinogenesis in humans. However, despite their importance, the mechanism by which many Snf2 proteins promote genome stability remains poorly understood. This represents not only a lack of understanding of a fundamental biological process but also a lost opportunity to manipulate genome stability processes for medical benefit.\r\n\r\nThere is significant interplay between Snf2-family proteins and the sumoylation pathway. Many chromatin remodelling enzymes are SUMO modified, and chromatin remodelling enzymes are required to mediate SUMO-directed transcriptional repression. Understanding the role of sumoylation in Snf2 function may provide an important means to modulate their function.\r\n\r\nUls1: a Snf2-family StUbl<\/strong><\/b>\r\n\r\nThe chromatin remodelling enzymes Uls1 has recently been show to have SUMO targeted ubiquitin ligase (STUbL) activity.\u00a0 Loss of Uls1 or inactivation of its ATPase activity results in strong sensitivity to the DNA intercalating drug acriflavine and subsequent activation of the DNA damage checkpoint. We are currently looking at Uls1\u2019s mechanism of action and how it contributes to genome stability.\r\n\r\nUsing C. elegans to understand ATRX<\/strong><\/b>\r\n\r\nMutation of ATRX in humans causes alpha-thalassemia, mental retardation (ATRX) syndrome and is also linked to a sub-type of cancers characterised by the alternative lengthening of telomeres (ALT) pathway. We are studying XNP-1, the worm homolog of ATRX, to better understand the connections between the developmental and telomeric roles of ATRX.","related_theme":false,"related_centre":[{"ID":77,"post_title":"Biomedical Sciences Research Complex","post_content":"The\u00a0Biomedical Sciences Research Complex (BSRC) is an interdisciplinary centre for biomedical research with contributions from the Schools of Biology, Chemistry, Medicine, Physics and Astronomy.\u00a0The BSRC's main research themes are infection and immunity, biophysics, molecular medicine, and chemical biology.\u00a0<\/span>\r\n\r\nMain Website<\/a>","post_excerpt":"","post_author":"4","post_date":"2022-01-17 15:53:50","post_date_gmt":"2022-01-17 15:53:50","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"biomedical-sciences-research-complex","to_ping":"","pinged":"","post_modified":"2022-09-20 13:31:47","post_modified_gmt":"2022-09-20 12:31:47","post_content_filtered":"","post_parent":0,"guid":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_centre&p=77","menu_order":0,"post_type":"research_centre","post_mime_type":"","comment_count":"0","comments":false,"id":77}],"contact":"Dr Helder Ferreira\r\nBiomolecular Sciences Building\r\nUniversity of St Andrews\r\nNorth Haugh\r\nSt Andrews\r\nKY16 9ST\r\nFife\r\nUK\r\n\r\ntel: 01334 463425\r\nfax: 01334 462495\r\nroom: B303\r\nemail:\u00a0hcf2@st-andrews.ac.uk<\/a>","_links":{"self":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/research_group\/169","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/research_group"}],"about":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/types\/research_group"}],"author":[{"embeddable":true,"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/users\/70"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/media\/170"}],"wp:attachment":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/media?parent=169"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}