{"id":305,"date":"2018-01-08T18:00:35","date_gmt":"2018-01-08T17:00:35","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/en\/?page_id=305"},"modified":"2024-02-16T13:15:36","modified_gmt":"2024-02-16T12:15:36","slug":"saspro-0063-01-02","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/en\/projects\/completed-projects\/saspro-0063-01-02\/","title":{"rendered":"SASPRO 0063\/01\/02"},"content":{"rendered":"<p><script type=\"text\/javascript\">\n<!--\nfunction launch(newURL, newName, newFeatures, orgName) {\n  var remote = open(newURL, newName, newFeatures);\n  if (remote.opener == null)\n    remote.opener = window;\n  remote.opener.name = orgName;\n  return remote;\n}\n\nfunction launchRemote(name) {\n  var address =  name;\n  myRemote = launch(address ,\n                    \"Okno\",\n                    \"height=500, width=850, left=50, top=50, alwaysLowered=0, alwaysRaised=0, channelmode=0, dependent=0, directories=0, fullscreen=0, hotkeys=1, location=0, menubar=0, resizable=0, scrollbars=0, status=0, titlebar=1, toolbar=0, z-lock=0\",\n                    \"myWindow\");\n}\n\/\/ -->>\n<\/script><\/p>\n<h2>Mitochondria-endoplasmic reticulum functional interplay in Wolfram Syndrome: emerging role for heart and brain protection&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<button onclick=\"goBack()\">Back<\/button> <\/h2>\n<p><script>\t \t \nfunction goBack() { window.history.go(-1); }\t \t \n<\/script><\/p>\n<table border=\"0\" width=\"100%\" cellspacing=\"1\" cellpadding=\"2\">\n<tbody>\n<tr>\n<td>\n<h3>Principal Investigator: <a href=\"http:\/\/confolab.sav.sk\/ovsb\/en\/people\/researchers\/rndr-michal-cagalinec-phd\/\">Michal Cagalinec<\/a><\/h3>\n<h3>Duration: March 2015 &#8211; December 2018<br \/>\nCoordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava (2015-2017); Institute of Experimental Endocrinology BRC SAS (2018)<\/h3>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Annotation:<\/span><\/h3>\n<p>Wolfram syndrome (WS) is a recessive neurological disorder caused by mutation of the Wfs1 gene. The Wfs1 protein is highly expressed in the brain and heart and is embedded in the endoplasmic reticulum (ER) where it modulates Ca2+ levels and ER stress. Additionally, the main symptoms of the WSare consistent with the ones characteristic for mitochondrial diseases. In fact, our preliminary results showed already that silencing of Wfs1 in mouse neurons decreased the mitochondrial fusion frequency and caused mitochondrial fragmentation, demonstrating strong impact of Wfs1 to mitochondrial function in neurons. Although the high expression of Wfs1 in the heart and cardiac symptoms in WS identified recently emphasize the functional importance of Wfs1 in the heart, the most common causes of morbidity in WS are the neurological manifestations.<\/p>\n<p>How is it possible that mutations of Wfs1 causing significant perturbations in the brain functions are not so prominent in the heart? One explanation of this tissue specificity is that a mechanism compensating for loss of Wfs1 protein function is present in the heart but not in neurons.<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Keywords:<\/span><\/h3>\n<p>Wolfram Syndrome, ventricular myocyte, heart, mitochondria, endoplasmic reticulum, neuron<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Objectives:<\/span><\/h3>\n<p>In this project we propose to study if the knockout of the Wfs1 gene in mice leads to disturbance in contractile properties of the heart both at organ and cell level. As Wfs1 impacts mitochondrial dynamics and morphology in neurons, we plan to analyse mitochondrial dynamics and ultrastructure in Wfs1 deficient myocytes. To understand the functional link of Wfs1 to mitochondria in neurons and myocytes we aim to answer if this link is mediated by direct ER-mitochondria interaction and\/or by calcium. Mitochondria-ER contact sites will be analysed by electron microscopy. The role of calcium will be elucidated by measuring of myocyte cytoplasmic calcium transients using confocal microscopy and the interaction of Wfs1 with the two most abundant calcium channels in ER &#8211; the IP3- and ryanodine receptors will be resolved by methods of molecular biology.<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Publications:<\/span><\/h3>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<table class=\"list\" border=\"0\" width=\"100%\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30930784\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1111\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/FrontiersPhysiol-150x51.jpg\" alt=\"FrontiersPhysiol\" width=\"75\" height=\"17\" \/><\/a><\/td>\n<td class=\"two\"><strong>Cagalinec M<\/strong>, <strong>Zahradnikova A<\/strong>, <strong>Zahradnikova A Jr<\/strong>, Kovacova D, Paulis L, <strong>Kurekova S<\/strong>, <strong>Hotka M<\/strong>, <strong>Pavelkova J<\/strong>, Plaas M, <strong>Novotova M<\/strong>, <strong>Zahradnik I<\/strong> (2019). <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30930784\")'>Calcium signaling and contractility in cardiac myocyte of wolframin deficient rats<\/a>. <i>Front Physiol<\/i> 10: 172, doi: 10.3389\/fphys.2019.00172.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30240113\")'><img decoding=\"async\" class=\"alignnone wp-image-1110\" src=\"http:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/CytometryPartA.png\" alt=\"SciRep\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\">Marcek Chorvatova A, Kirchnerova J, <strong>Cagalinec M<\/strong>, Mateasik A, Chorvat D Jr (2019): <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30240113\")'>Spectrally and spatially resolved laser-induced photobleaching of endogenous flavin fluorescence in cardiac myocytes<\/a>. <i>Cytometry Part A<\/i> 95: 13-23 doi: 10.1002\/cyto.a.23591.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27434582?dopt=Citation\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1110\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/PLOSBiology.jpg\" alt=\"PLoSBiology\" width=\"75\" height=\"19\" \/><\/a><\/td>\n<td class=\"two\"><strong>Cagalinec M<\/strong>, Liiv M, Hodurova Z, Hickey MA, Vaarmann A, Mandel M, Zeb A, Choubey V, Kuum M, Safiulina D, Vasar E, Veksler V, Kaasik A (2016): <a href='javascript:launchRemote(\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27434582?dopt=Citation\")'>Role of mitochondrial dynamics in neuronal development: Mechanism for wolfram syndrome<\/a>. <i>PLoS Biol<\/i> 14: e1002511.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>Mitochondria-endoplasmic reticulum functional interplay in Wolfram Syndrome: emerging role for heart and brain protection&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Back Principal Investigator: Michal Cagalinec Duration: March 2015 &#8211; December 2018 Coordinating&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/en\/projects\/completed-projects\/saspro-0063-01-02\/\">\u010d\u00edta\u0165 \u010falej &raquo;<\/a><\/span><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":199,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/305"}],"collection":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/comments?post=305"}],"version-history":[{"count":9,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/305\/revisions"}],"predecessor-version":[{"id":1603,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/305\/revisions\/1603"}],"up":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/199"}],"wp:attachment":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/media?parent=305"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}