{"id":1222,"date":"2020-01-09T15:07:46","date_gmt":"2020-01-09T15:07:46","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/?page_id=1222"},"modified":"2023-10-06T12:12:31","modified_gmt":"2023-10-06T12:12:31","slug":"jrp-2019-836-ryrinheart","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/jrp-2019-836-ryrinheart\/","title":{"rendered":"JRP\/2019\/836\/RyRinHeart"},"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>RyRinHeart &#8211; V\u00fdvoj inhib\u00edtorov ryanod\u00ednov\u00e9ho receptora pre srdcov\u00e9 ochorenia &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\/ing-alexandra-zahradnikova-drsc\/\">Alexandra Zahradn\u00edkov\u00e1<\/a><\/h3>\n<h3>Trvanie: janu\u00e1r 2020 \u2013 december 2022<br \/>\nKoordinuj\u00faca organiz\u00e1cia: \u00dastav experiment\u00e1lnej endokrinol\u00f3gie BMC SAV, Bratislava<\/h3>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Anot\u00e1cia:<\/span><\/h3>\n<p>Srdcov\u00e9 ryanod\u00ednov\u00e9 receptory (RyR2) riadia kontrakciu srdca t\u00fdm, \u017ee reguluj\u00fa uvo\u013e\u0148ovanie v\u00e1pnika, potrebn\u00e9ho pre kontrakciu srdcov\u00fdch myocytov. Mnoh\u00e9 srdcov\u00e9 ochorenia s\u00fa sprev\u00e1dzan\u00e9 poruchami uvo\u013e\u0148ovania v\u00e1pnika. Tieto poruchy by bolo mo\u017en\u00e9 potla\u010di\u0165 lie\u010divami zabra\u0148uj\u00facimi ne\u017eelanej aktivite RyR2. Cie\u013eom tohto projektu je v\u00fdvoj \u0161pecifick\u00fdch inhib\u00edtorov, prisp\u00f4soben\u00fdch \u0161trukt\u00fare srdcov\u00e9ho RYR2, s potenci\u00e1lom pre lie\u010denie por\u00fach hospod\u00e1renia s v\u00e1pnikom pri srdcov\u00fdch ochoreniach.<br \/>\nNa\u0161e origin\u00e1lne poznatky o \u0161trukt\u00fare RYR2 vyu\u017eijeme na identifik\u00e1ciu lokusov v 3D-\u0161trukt\u00fare RyR2, ktor\u00e9 pri naviazan\u00ed ligandu zni\u017euj\u00fa aktivitu RyR. To n\u00e1m umo\u017en\u00ed dizajnova\u0165 a syntetizova\u0165 inhib\u00edtory RyR2. Ich \u00fa\u010dinnos\u0165 budeme testova\u0165 v experimentoch monitoruj\u00facich aktivitu RyR. \u00da\u010dinnos\u0165 vybran\u00fdch najperspekt\u00edvnej\u0161\u00edch l\u00e1tok na funkciu RyR2 in situ budeme testova\u0165 na izolovan\u00fdch srdcov\u00fdch  myocytoch a fin\u00e1lne na srdciach zdrav\u00fdch zvierat a zvierat so srdcov\u00fdm ochoren\u00edm.<br \/>\nMetodicky je projekt zalo\u017een\u00fd na 2 pilieroch: na simul\u00e1ci\u00e1ch molekulovej \u0161trukt\u00fary, molekulovej dynamiky a po\u010d\u00edta\u010dom asistovanom dizajne lie\u010div, kde hlavn\u00fdm nosite\u013eom expert\u00edzy je tureck\u00e1 strana, a na \u0161irokej palete experiment\u00e1lnych a teoretick\u00fdch met\u00f3d \u0161t\u00fadia i\u00f3nov\u00fdch kan\u00e1lov a v\u00e1pnikovej signaliz\u00e1cie (biochemick\u00e9 a elektrofyziologick\u00e9 met\u00f3dy, konfok\u00e1lna mikroskopia, matematick\u00e9 modelovanie dynamiky vn\u00fatrobunkov\u00fdch procesov), kde zabezpe\u010duje expert\u00edzu slovensk\u00e1 strana.<br \/>\nProjekt si kladie za cie\u013e prispie\u0165 k rie\u0161eniu v\u00e1\u017eneho medic\u00ednskeho probl\u00e9mu  pomocou pokro\u010dil\u00fdch technol\u00f3gii, origin\u00e1lnej expert\u00edzy a nov\u00fdch pr\u00edstupov vyvinut\u00fdch v spolupracuj\u00facich laborat\u00f3ri\u00e1ch.\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">K\u013e\u00fa\u010dov\u00e9 slov\u00e1:<\/span><\/h3>\n<p>ryanod\u00ednov\u00fd receptor, kardiomyocyt, v\u00e1pnikov\u00e1 signaliz\u00e1cia, dizajn a testovanie lie\u010div, molekul\u00e1rne modelovanie, matematick\u00e9 modelovanie, srdcov\u00e9 ochorenia <\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Ciele:<\/span><\/h3>\n<p>Cie\u013eom projektu je dizajnovanie a testovanie l\u00e1tky zabra\u0148uj\u00facej tvorbe arytmi\u00ed pri po\u0161koden\u00ed v\u00e1pnikovej signaliz\u00e1cie v d\u00f4sledku srdcov\u00fdch ochoren\u00ed. Na dosiahnutie tohto cie\u013ea sme si vyt\u00fd\u010dili nasledovn\u00e9 \u0161pecifick\u00e9 ciele:<\/p>\n<ul>\n<li> pomocou biochemick\u00fdch a biofyzik\u00e1lnych met\u00f3d z\u00edska\u0165 inform\u00e1cie o mechanizme inhib\u00edcie RyR2 zn\u00e1mymi inhib\u00edtormi; <\/li>\n<li> pomocou molekul\u00e1rneho modelovania a po\u010d\u00edta\u010dov\u00e9ho dizajnu  lie\u010div navrhn\u00fa\u0165 a pomocou biochemick\u00fdch a biofyzik\u00e1lnych met\u00f3d testova\u0165 l\u00e1tky, v ktor\u00fdch je optimalizovan\u00e9 vyu\u017eitie mechanizmu inhib\u00edcie na zabr\u00e1nenie ne\u017eelan\u00e9ho uvo\u013e\u0148ovania v\u00e1pnika v kardiomyocytoch <\/li>\n<li> otestova\u0165 \u00fa\u010dinok l\u00e1tky, ktor\u00e1 poskytne najlep\u0161ie v\u00fdsledky na bunkovej \u00farovni, na in vivo modeli srdcov\u00e9ho ochorenia u my\u0161\u00ed. <\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<tr>\n<td><\/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\/36609141\/\")'><img decoding=\"async\" class=\"alignnone wp-image-1111\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/BiophysJnew.jpg\" alt=\"FrontiersPhysiol\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\"><strong>Baglaeva I<\/strong>, <strong>Iaparov B<\/strong>, <strong>Zahradnik I<\/strong>, <strong>Zahradnikova A<\/strong> (2023). <a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36609141\/\")'>Analysis of noisy transient signals based on Gaussian process regression<\/a>. <i>Biophys J<\/i> 122: 451\u2013459. doi: 10.1016\/j.bpj.2023.01.003.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/35145426\/\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1111\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/FrontiersPhysiol.jpg\" alt=\"FrontiersPhysiol\" width=\"75\" height=\"17\" \/><\/a><\/td>\n<td class=\"two\"><strong>Iaparov B<\/strong>, <strong>Baglaeva I<\/strong>, <strong>Zahradnik I<\/strong>, <strong>Zahradnikova A<\/strong> (2022). <a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/35145426\/\")'>Magnesium ions moderate calcium-induced calcium release in cardiac calcium release sites by binding to ryanodine receptor activation and inhibition sites<\/a>. <i>Front Physiol<\/i> 12: 805956. doi: 10.3389\/fphys.2021.805956.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\" width=\"5%\"><a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33735373\/\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1114\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/m_jgp_2021_153_4.cover_.png\" alt=\"JGP\" width=\"80\" height=\"104\" \/><\/a><\/td>\n<td class=\"two\"><strong>Iaparov B<\/strong>, <strong>Zahradnik I<\/strong>, Moskvin AS, <strong>Zahradnikova A<\/strong> (2021): <a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33735373\/\")'>In silico simulations reveal that RYR distribution affects the dynamics of calcium release in cardiac myocytes<\/a>. <i>J Gen Physiol<\/i> 153: e202012685 doi: 10.1085\/jgp.202012685.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.biorxiv.org\/content\/10.1101\/2020.08.26.260968v1\")'><img decoding=\"async\" class=\"alignnone wp-image-1111\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/bioRxiv_article.jpg\" alt=\"Prog Biophys Mol Biol\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\"> <strong>Iaparov B<\/strong>, <strong>Zahradnik I<\/strong>, Moskvin AS, <strong>Zahradnikova A<\/strong> (2020): <a href='javascript:launchRemote(\"https:\/\/www.biorxiv.org\/content\/10.1101\/2020.08.26.260968v1\")'>Synergy of calcium release site determinants in control of calcium release events in cardiac myocytes<\/a>. <i>bioRXiv<\/i> :  doi: https:\/\/doi.org\/10.1101\/2020.08.26.260968.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32416189\")'><img decoding=\"async\" class=\"alignnone wp-image-1111\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/ProgBiophysMolBiol-e1590139461171.jpg\" alt=\"Prog Biophys Mol Biol\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\"><strong>Zahradnikova A<\/strong>, <strong>Iaparov B<\/strong>, <strong>Zahradnik I<\/strong> (2020): <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32416189\")'>The problem of accuracy in single-channel open probability measurements<\/a>. <i>Prog Biophys Mol Biol<\/i> 157: 94-106 doi: 10.1016\/j.pbiomolbio.2020.05.002.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>RyRinHeart &#8211; V\u00fdvoj inhib\u00edtorov ryanod\u00ednov\u00e9ho receptora pre srdcov\u00e9 ochorenia &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Nasp\u00e4\u0165 Ved\u00faci projektu: Alexandra Zahradn\u00edkov\u00e1 Trvanie: janu\u00e1r 2020 \u2013 december 2022 Koordinuj\u00faca organiz\u00e1cia: \u00dastav experiment\u00e1lnej endokrinol\u00f3gie&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/jrp-2019-836-ryrinheart\/\">\u010d\u00edta\u0165 \u010falej &raquo;<\/a><\/span><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":117,"menu_order":50,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/1222"}],"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=1222"}],"version-history":[{"count":20,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/1222\/revisions"}],"predecessor-version":[{"id":2552,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/1222\/revisions\/2552"}],"up":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/117"}],"wp:attachment":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/media?parent=1222"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}