{"id":175,"date":"2022-09-08T09:58:15","date_gmt":"2022-09-08T08:58:15","guid":{"rendered":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_group&#038;p=175"},"modified":"2022-12-21T10:25:53","modified_gmt":"2022-12-21T10:25:53","slug":"judith-sleeman","status":"publish","type":"research_group","link":"https:\/\/biology.st-andrews.ac.uk\/research\/research-group\/judith-sleeman\/","title":{"rendered":"Judith Sleeman"},"content":{"rendered":"<p>Our group is based in the interdisciplinary<span>\u00a0<\/span><a href=\"http:\/\/www.st-andrews.ac.uk\/bsrc\/\">Biomedical Sciences Research Complex<\/a>.<\/p>\n<p>The mammalian cell<span>\u00a0<\/span><span class=\"Apple-style-span\">nucleus<\/span><span>\u00a0<\/span>has a highly ordered structure. The detailed organisation of the nucleus and how this affects its function are not fully understood. Essential to the expression, or functioning, of genes are \u2018transcription\u2019 of the DNA instructions into a messenger RNA (mRNA) intermediate and \u2018translation\u2019 of this into the protein \u2018product\u2019 of the gene. Almost all mammalian genes contain introns, which are sequences represented in the DNA but not in the protein. These must be removed, or \u2018spliced\u2019, from the mRNA message before it can be translated. The accuracy of mRNA splicing is essential for correct gene expression.<\/p>\n<p><span class=\"Apple-style-span\">snRNPs<\/span><span>\u00a0<\/span>(small nuclear ribonucleoproteins) are essential splicing factors and show a complex pattern of distribution within the nucleus. They localise to a number of nuclear domains including<span>\u00a0<\/span><span class=\"Apple-style-span\">speckles<\/span><span>\u00a0<\/span>and<span>\u00a0<\/span><span class=\"Apple-style-span\">Cajal bodies<\/span>. The formation of snRNPs is a complex process. Early steps occur outside the nucleus in the cytoplasm, and require a protein called Survival of Motor Neurons (SMN).<\/p>\n<p>Insufficient expression of SMN is responsible for the inherited neurodegenerative disease, spinal muscular atrophy (SMA). SMN is also found in the nucleus where it concentrates, along with snRNPs, in Cajal bodies. It is not clear how the loss of SMN protein leads to the disease. All cells need to splice their RNA correctly, but SMA specifically affects motor neurons. It is also possible that SMN is needed to transport mature mRNAs within cells and that this function is particularly important in motor neurons becuase of their immense length.<\/p>\n<p>We study the maturation of snRNP splicing factors and the transport of mature mRNA, with a particular emphasis on their dynamics within the nucleus and differences between neural and non-neural cell types that may be significant for SMA.<\/p>\n<p><a href=\"http:\/\/www.st-andrews.ac.uk\/bsrc\/\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-68 size-full\" src=\"https:\/\/sleeman.wp.st-andrews.ac.uk\/files\/2015\/11\/BSRC-0.png\" sizes=\"auto, (max-width: 928px) 100vw, 928px\" srcset=\"https:\/\/sleeman.wp.st-andrews.ac.uk\/files\/2015\/11\/BSRC-0.png 928w, https:\/\/sleeman.wp.st-andrews.ac.uk\/files\/2015\/11\/BSRC-0-300x73.png 300w, https:\/\/sleeman.wp.st-andrews.ac.uk\/files\/2015\/11\/BSRC-0-768x187.png 768w\" alt=\"\" width=\"928\" height=\"226\" \/><\/a><\/p>\n<p>For Spinal Muscular Atrophy information and support, please click<span>\u00a0<\/span><a href=\"http:\/\/www.smasupportuk.org.uk\/\">here<\/a>.<\/p>\n<p>&nbsp;<\/p>\n<p>Our group website: https:\/\/sleeman.wp.st-andrews.ac.uk\/<\/p>\n","protected":false},"excerpt":{"rendered":"<p>We study the maturation of snRNP splicing factors and the transport of mature mRNA, with a particular emphasis on their dynamics within the nucleus and differences between neural and non-neural cell types that may be significant for SMA.<\/p>\n","protected":false},"author":30,"featured_media":176,"parent":0,"menu_order":0,"template":"","class_list":["post-175","research_group","type-research_group","status-publish","has-post-thumbnail","hentry"],"jetpack_sharing_enabled":true,"group_members":"","publications":"[publications flag='individual' code='jes14' dois='1' max='10' categorise='1']","research_projects":"<span>Our recent research has been expanding from its original focus on nuclear dynamics and splicing snRNP maturation to look at broader connections between RNA metabolism and inherited disease. We are predominantly interested in Spinal Muscular Atrophy, and have also published data on the dynamics of pathological nuclear RNA foci seen in Myotonic Dystrophy Type 1.<\/span>\r\n\r\n<span>We have pioneered the use of a combination of quantitative proteomics and timed expression of GFP-tagged proteins to dissect stages of splicing snRNP maturation. This has led us to identify a novel cytoplasmic structure implicated in SMA pathology and provided insight into the complexity of interactions between SMN and splicing factors of relevance to SMA.<\/span>\r\n\r\n<a href=\"https:\/\/sleeman.wp.st-andrews.ac.uk\/publications\/\">Publications<\/a>","related_theme":false,"related_centre":[{"ID":77,"post_title":"Biomedical Sciences Research Complex","post_content":"<span>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\n<a href=\"https:\/\/biology.st-andrews.ac.uk\/bsrc\">Main 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&#038;p=77","menu_order":0,"post_type":"research_centre","post_mime_type":"","comment_count":"0","comments":false,"id":77}],"contact":"Judith Sleeman\r\n\r\njes14@st-andrews.ac.uk","_links":{"self":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/research_group\/175","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\/30"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/media\/176"}],"wp:attachment":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/media?parent=175"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}