{"id":681,"date":"2019-01-14T09:56:01","date_gmt":"2019-01-14T08:56:01","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/en\/?page_id=681"},"modified":"2023-02-22T12:24:21","modified_gmt":"2023-02-22T11:24:21","slug":"vega-2-0121-19","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/en\/projects\/completed-projects\/vega-2-0121-19\/","title":{"rendered":"VEGA 2\/0121\/19"},"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>Dominant mutations in Wolfram syndrome: different mechanism to the recessive ones?&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: January 2019 &#8211; December 2022<br \/>\nCoordinating Organization: Institute of Experimental Endocrinology BRC SAS<\/h3>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Annotation:<\/span><\/h3>\n<p>Wolfram syndrome is a rare hereditary disorder caused by mutations in the Wolframin1 gene. Product of this gene, the Wolframin1 (WFS1) is located in the membrane of endoplasmic reticulum (ER). WFS1 is highly expressed in pancreas, brain and heart. Function of WFS1 involves regulation of ER stress and modulation in calcium homeostasis. Moreover it affects mitochondrial dynamics and ATP production in neurons. Although Wolfram syndrome is traditionally considered as recessive disorder, in our patients, we have identified two novel mutations of WFS1 resembling dominant behaviour. Therefore in this project we plan to evaluate, whether these novel mutations of  are dominant and whether dominant and recessive mutations in the WFS1 gene act via different signalling pathways in the matter of ER stress, calcium metabolism and their impact to mitochondrial dynamics. These parameters will be tested in a model of human neuronal and cardiac cell lines to reveal unique mechanisms of WFS1 function in the brain and heart.<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Keywords:<\/span><\/h3>\n<p>Wolfram syndrome, Wolframin1, dominant and recessive mutations, calcium homeostasis, endoplasmic reticulum stress, mitochondrial dynamics<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Objectives:<\/span><\/h3>\n<p>Main hypothesis of the project: whether the novel mutations in WFS1 identified in our patients with Wolfram Syndrome (WS) are dominant and to test, whether the dominant mutations in this gene act through different mechanism when compared to recessive mutations in respect of ER stress, calcium metabolism and mitochondrial dynamics in human neuronal and cardiac cellular models.<\/p>\n<p>Particular goals:<\/p>\n<ul>\n<li> to generate the particular plasmids carrying the selected dominant and recessive WFS1 mutations. After this, using a neuronal cell model, namely the SHSY-5Y cells, and a cardiac myocyte cell line, the H9C2 cells, transfected with the generated plasmids with dominant as well as recessive WFS1 mutations <\/li>\n<li> to resolve the ER stress pathway induced by novel mutations in WFS1 and to reveal differences in the ER stress pathway when comparing recessive and dominant mutations in WFS1 <\/li>\n<li> to address the calcium signalling pathway in novel mutations in WFS1 and compare recessive and dominant mutations in WFS1 <\/li>\n<li> to reveal the impact of the novel mutations on mitochondrial dynamics and compare affect of recessive and dominant mutations in WFS1 also in this aspect <\/li>\n<\/ul>\n<\/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:\/\/pubmed.ncbi.nlm.nih.gov\/34118053\/\")'><img decoding=\"async\" loading=\"lazy\" width=\"75\" height=\"104\" class=\"alignnone\" src=\"http:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/Mitochondrial_Medicine.jpg\"><\/a><\/td>\n<td class=\"two\">Marcek Chorvatova A, <strong>Cagalinec M<\/strong>, Chorvat D Jr (2021): <a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34118053\/\")'>Time-resolved imaging of mitochondrial flavin fluorescence and its applications for evaluating the oxidative state in living cardiac cells<\/a>. <i>Mitochondrial Medicine. Methods in Molecular Biology<\/i>, vol 2275, chapter 26: 403-414. Humana, New York, NY. Volume 1: Targeting Mitochondria, Weissig V., Edeas M. (eds), ISBN 978-1-0716-1262-0, doi: 10.1007\/978-1-0716-1262-0_26.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33084603\/\")'><img decoding=\"async\" loading=\"lazy\" width=\"75\" height=\"104\" class=\"alignnone\" src=\"http:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/GPB-1.jpg\"><\/a><\/td>\n<td class=\"two\">Kurekova S, Plaas M, <strong>Cagalinec M<\/strong> (2020): <a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33084603\/\")'>Short Communication: Lack of functional wolframin causes drop in  plasmalemmal sodium-calcium exchanger type  1 expression at  early stage in  rat model of  Wolfram syndrome<\/a>. <i>Gen Physiol Biophys<\/i> 39: 499\u2013503 doi: 10.4149\/gpb_2020017.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>Dominant mutations in Wolfram syndrome: different mechanism to the recessive ones?&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Back Principal Investigator: Michal Cagalinec Duration: January 2019 &#8211; December 2022 Coordinating Organization: Institute of&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/en\/projects\/completed-projects\/vega-2-0121-19\/\">\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\/681"}],"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=681"}],"version-history":[{"count":9,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/681\/revisions"}],"predecessor-version":[{"id":1249,"href":"https:\/\/confolab.sav.sk\/ovsb\/en\/wp-json\/wp\/v2\/pages\/681\/revisions\/1249"}],"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=681"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}