{"id":2258,"date":"2022-05-12T11:15:58","date_gmt":"2022-05-12T11:15:58","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/?page_id=2258"},"modified":"2024-07-24T14:01:15","modified_gmt":"2024-07-24T14:01:15","slug":"apvv-21-0473","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/projekty\/aktivne-projekty\/apvv-21-0473\/","title":{"rendered":"APVV-21-0473"},"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>Mut\u00e1cie asociovan\u00e9 s Wolframov\u00fdm syndr\u00f3mom: rozdielne sign\u00e1lne dr\u00e1hy v zmysle metabolizmu v\u00e1pnika a funkcie mitochondri\u00ed &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<button onclick=\"goBack()\">Nasp\u00e4\u0165<\/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>Ved\u00faci projektu: <a href=\"https:\/\/confolab.sav.sk\/ovsb\/pracovnici\/vyskumnici\/rndr-michal-cagalinec-phd\/\">Michal Cagalinec<\/a><\/h3>\n<h3>Trvanie: 1. j\u00fal 2022 &#8211; 30. j\u00fan 2026<br \/>\nKoordinuj\u00faca organiz\u00e1cia: \u00dastav experiment\u00e1lnej endokrinol\u00f3gie BMC, v.v.i. SAV, Bratislava<br \/>\nSpolurie\u0161ite\u013esk\u00e1 organiz\u00e1cia: \u00dastav molekul\u00e1rnej fyziol\u00f3gie a genetiky CBv, v.v.i. SAV, Bratislava<\/h3>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Anot\u00e1cia:<\/span><\/h3>\n<p>Wolframov syndr\u00f3m (WS), diagnostikovan\u00fd na z\u00e1klade diabetes insipidus, diabetes mellitus, atrofie optick\u00e9ho nervu a hluchoty, je sp\u00f4soben\u00fd mut\u00e1ciami v g\u00e9ne WFS1. V s\u00falade s t\u00fdmito pr\u00edznakmi, prote\u00edn WFS1 je vo vysokej miere produkovan\u00fd v mozgu a pankrease. Okrem toho je pop\u00edsan\u00e1 jeho vysok\u00e1 expres ia aj v srdci; prekvapivo v\u0161ak vo ve\u013ekej v\u00e4\u010d\u0161ine pr\u00edpadov pr\u00edznaky na srdci pozorovan\u00e9 neboli. WFS1 predstavuje intergr\u00e1lny prote\u00edn membr\u00e1ny endoplazmatick\u00e9ho retikula (ER) s v\u00fdrazn\u00fdm vplyvom na metabolizmus v\u00e1pnika, funkciu mitochondri\u00ed a stres ER. Otvorenou ot\u00e1zkou v\u0161ak ost\u00e1va, pre\u010do s\u00fa \u03b2-bunky pankreasu a neur\u00f3ny pri WS silne po\u0161koden\u00e9 a zmeny v myocytoch s\u00fa iba minim\u00e1lne, ke\u010f je v nich WFS1 vysoko exprimovan\u00fd? Vysvetlen\u00edm by mohol by\u0165 zatia\u013e nezn\u00e1my kompenza\u010dn\u00fd mechanizmus pr\u00edtomn\u00fd v myocytoch a\/alebo odli\u0161n\u00e9 sign\u00e1lne dr\u00e1hy, ktor\u00e9 nie s\u00fa pr\u00edtomn\u00e9 v neur\u00f3noch\/\u03b2-bunk\u00e1ch. Preto prv\u00e1 hypot\u00e9za znie: L\u00ed\u0161i sa metabolizmus v\u00e1pnika a funkcia mitochondri\u00ed v srdcov\u00fdch myocytoch v porovnan\u00ed s neur\u00f3nmi a pankreatick\u00fdmi \u03b2-bunkami v pr\u00edpade po\u0161kodenia WFS1? V\u00e4\u010d\u0161ina pr\u00edpadov WS predstavuje reces\u00edvne mut\u00e1cie; bolo v\u0161ak identifikovan\u00fdch aj nieko\u013eko dominantn\u00fdch mut\u00e1ci\u00ed. Druh\u00e1 hypot\u00e9za preto znie: L\u00ed\u0161i sa metabolizmus v\u00e1pnika a mitochondri\u00e1lna dynamika v bunk\u00e1ch exprimuj\u00facich patog\u00e9nne dominantn\u00e9 vo\u010di reces\u00edvnym mut\u00e1ci\u00e1m prote\u00ednu WFS1? \u00dapln\u00fdm unik\u00e1tom projektu je charakteriz\u00e1cia doteraz nepozorovan\u00e9ho heterozygotn\u00e9ho dele\u010dn\u00e9ho variantu WFS1, ktor\u00fd bol len ned\u00e1vno identifikovan\u00fd u prv\u00e9ho slovensk\u00e9ho pacienta s WS na \u00fastave \u017eiadate\u013ea a jeho funk\u010dn\u00e9 porovnanie s dominantn\u00fdmi a reces\u00edvnymi variantmi. Vyu\u017eitie modern\u00fdch pr\u00edstupov vr\u00e1tane met\u00f3dy CRISPR\/Cas9, optogenetick\u00fdch techn\u00edk, konfok\u00e1lnej mikroskopie a know-how navrhovan\u00e9ho v\u00fdskumn\u00e9ho t\u00edmu pom\u00f4\u017ee, aspo\u0148 \u010diasto\u010dne, objasni\u0165 funkciu WFS1, \u010do v dlhodobom horizonte posl\u00fa\u017ei pre v\u00fdvoj v\u010dasnej diagnostiky a efekt\u00edvnej lie\u010dby nielen pacientov trpiacich WS, ale aj pacientov s diabetes mellitus a kardiovaskul\u00e1rnymi ochoreniami s vysokou prevalenciou.<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">K\u013e\u00fa\u010dov\u00e9 slov\u00e1:<\/span><\/h3>\n<p>diabetes, neurodegenerat\u00edvne ochorenia, Wolframov syndr\u00f3m, Wolfram\u00edn1, metabolizmus v\u00e1pnika, morfol\u00f3gia mitochondri\u00ed, mitochondri\u00e1lna dynamika, konfok\u00e1lna mikroskopia, Crispr\/Cas9, elektr\u00f3nov\u00e1 mikroskopia, imunofluorescencia, plan\u00e1rne lipidov\u00e9 dvojvrstvy<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Ciele:<\/span><\/h3>\n<p>Hlavn\u00e1 hypot\u00e9za navrhovan\u00e9ho projektu je, \u010di a ako sa men\u00ed:<br \/>\n1. metabolizmus v\u00e1pnika a mitochondri\u00e1lna dynamika v srdcov\u00fdch myocytoch v porovnan\u00ed s neur\u00f3nmi a beta\u0002bunkami pankreasu v pr\u00edpade poruchy funkcie prote\u00ednu Wolframin1 a<br \/>\n2. metabolizmus v\u00e1pnika a mitochondri\u00e1lna dynamika pri patog\u00e9nnych dominantn\u00fdch vs. reces\u00edvnych pacientsk\u00fdch mut\u00e1ci\u00e1ch prote\u00ednu Wolframin1.\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Publik\u00e1cie:<\/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\/39034309\/\")'><img decoding=\"async\" class=\"alignnone wp-image-1111\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/NatureComunication.jpg\" alt=\"FrontiersPhysiol\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\">Liiv M, Vaarmann A, Safiulina D, Choubey V, Gupta R, Kuum M, Janickova L, Hodurova Z, <strong>Cagalinec M<\/strong>, Zeb A, Hickey MA, Huang YL, Gogichaishvili N, Mandel M, Plaas M, Vasar E, Loncke J, Vervliet T, Tsai TF, Bultynck G, Veksler V, Kaasik A (2024). <a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39034309\/\")'>ER calcium depletion as a key driver for impaired ER-to-mitochondria calcium transfer and mitochondrial dysfunction in Wolfram syndrome.<\/a>. <i>Nat Commun<\/i> 15: 6143. doi: 10.1038\/s41467-024-50502-x.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>Mut\u00e1cie asociovan\u00e9 s Wolframov\u00fdm syndr\u00f3mom: rozdielne sign\u00e1lne dr\u00e1hy v zmysle metabolizmu v\u00e1pnika a funkcie mitochondri\u00ed &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Nasp\u00e4\u0165 Ved\u00faci projektu: Michal Cagalinec Trvanie: 1. j\u00fal 2022 &#8211;&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/projekty\/aktivne-projekty\/apvv-21-0473\/\">\u010d\u00edta\u0165 \u010falej &raquo;<\/a><\/span><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":116,"menu_order":70,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/2258"}],"collection":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/comments?post=2258"}],"version-history":[{"count":8,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/2258\/revisions"}],"predecessor-version":[{"id":2681,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/2258\/revisions\/2681"}],"up":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/116"}],"wp:attachment":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/media?parent=2258"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}