{"id":542,"date":"2018-01-10T15:10:50","date_gmt":"2018-01-10T15:10:50","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/?page_id=542"},"modified":"2023-10-06T12:13:51","modified_gmt":"2023-10-06T12:13:51","slug":"apvv-16-0452","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/apvv-16-0452\/","title":{"rendered":"APVV-16-0452"},"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>Regul\u00e1cia pericelul\u00e1rnej proteol\u00fdzy: od molekul\u00e1rnych mechanizmov k nov\u00fdm subsetom imunitn\u00fdch buniek a terapeutick\u00fdm n\u00e1strojom (PPIS) &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>Koordin\u00e1tor: Vladim\u00edr Leksa<\/h3>\n<h3>Ved\u00faci projektu za BMC SAV: <a href=\"https:\/\/confolab.sav.sk\/ovsb\/pracovnici\/vyskumnici\/rndr-alexandra-zahradnikova-ml-phd\/\">Alexandra Zahradn\u00edkov\u00e1 ml.<\/a><\/h3>\n<h3>Trvanie: j\u00fal 2017 &#8211; j\u00fan 2021<br \/>\nKoordinuj\u00faca organiz\u00e1cia: \u00dastav molekul\u00e1rnej biol\u00f3gie SAV, Bratislava<\/h3>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Anot\u00e1cia:<\/span><\/h3>\n<p>Plazminog\u00e9nov\u00fd syst\u00e9m patr\u00ed medzi hlavn\u00e9 proteolytick\u00e9 syst\u00e9my. Je zapriahnut\u00fd v mnoh\u00fdch fyziologick\u00fdch procesoch, zvl\u00e1\u0161 v imunitn\u00fdch odpovediach. Celkov\u00fdm cie\u013eom tohto projektu je pop\u00edsa\u0165 nov\u00e9 molekul\u00e1rne mechanizmy kontroluj\u00face plazminog\u00e9nov\u00fa aktiv\u00e1ciu po\u010das procesov z\u00edskanej aj vrodenej imunity, konkr\u00e9tne pri T bunkovej migr\u00e1cii, aktiv\u00e1cii cytok\u00ednov a pri udr\u017eiavan\u00ed homeost\u00e1zy prostredn\u00edctvom makrof\u00e1gov. Projekt vych\u00e1dza nielen z na\u0161ich publikovan\u00fdch \u0161t\u00fadi\u00ed, ale aj z ned\u00e1vnych nepublikovan\u00fdch objavov a s\u013eubn\u00fdch predbe\u017en\u00fdch v\u00fdsledkov \u0160pecifick\u00e9 ciele projektu nie s\u00fa od seba nez\u00e1visl\u00e9, s\u00fa navz\u00e1jom prepojen\u00e9 nielen na \u00farovni bunkov\u00fdch a molekul\u00e1rnych mechanizmov, ale aj na \u00farovni experiment\u00e1lnych pr\u00edstupov a metod\u00edk Hlavn\u00fdm v\u00fdstupom projektu bude nielen hlb\u0161ie pochopenie molekul\u00e1rnych mechanizmov plazminog\u00e9novej aktiv\u00e1cie a charakteriz\u00e1cia imunitn\u00fdch buniek, ktor\u00e9 tieto mechanizmy vyu\u017e\u00edvaj\u00fa, konkr\u00e9tne subpopul\u00e1cie T buniek a makrof\u00e1gov, ale aj nov\u00e9 molekul\u00e1rne n\u00e1stroje na farmakologick\u00fa \u00fapravu nevyv\u00e1\u017eenej plazminog\u00e9novej aktiv\u00e1cie, ktor\u00e1 je asociovan\u00e1 s mnoh\u00fdmi \u013eudsk\u00fdmi ochoreniami, napr\u00edklad s chronick\u00fdmi z\u00e1palov\u00fdmi \u010di n\u00e1dorov\u00fdmi ochoreniami Dosiahnut\u00e9 v\u00fdsledky projektu bud\u00fa nepochybne d\u00f4le\u017eit\u00e9 nielen pre vedcov z\u00e1kladn\u00e9ho v\u00fdskumu, ale aj pre lek\u00e1rov a farmakologick\u00e9 spolo\u010dnosti.<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">K\u013e\u00fa\u010dov\u00e9 slov\u00e1:<\/span><\/h3>\n<p>z\u00edskan\u00e1 imunita, vroden\u00e1 imunita, pericelul\u00e1rna proteol\u00fdza, bunkov\u00e1 migr\u00e1cia, TGF-beta, eferocyt\u00f3za, T bunky, makrof\u00e1gy, receptor pre man\u00f3za-6 fosf\u00e1t a inzul\u00ednu podobn\u00fd rastov\u00fd faktor 2 &#8211; M6P\/IGF2R, receptor pre plazminog\u00e9nov\u00fd aktiv\u00e1tor urokin\u00e1zov\u00e9ho typu &#8211; u AR, bunkov\u00fd subset<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Ciele:<\/span><\/h3>\n<p>Hlavn\u00fd cie\u013e #1: Adapt\u00edvny imunitn\u00fd syst\u00e9m \u2013 \u0161t\u00fadium plazminog\u00e9nov\u00e9ho syst\u00e9mu pri funkci\u00e1ch T buniek: v tejto \u010dasti projektu, chceme<br \/>\n(i) sk\u00fama\u0165, \u010di M6 \/IGF2R-u AR pozit\u00edvny subset T buniek vyu\u017e\u00edva tento komplex pre kontrolu migr\u00e1cie T buniek a\/alebo aktiv\u00e1ciu latentn\u00e9ho TGF-beta;<br \/>\n(ii) detailne charakterizova\u0165 t\u00fato M6 \/IGF2Ru AR pozit\u00edvnu subpopul\u00e1ciu T-buniek;<br \/>\n(iii) poskytn\u00fa\u0165 molekul\u00e1rne n\u00e1stroje pre farmakologick\u00fa modul\u00e1ciu t\u00fdchto procesov.<\/p>\n<p>\u0160pecifick\u00e9 ciele:<br \/>\n1a) Optimaliz\u00e1cia \u0161pecifick\u00fdch peptidov a monoklon\u00e1lnych protil\u00e1tok<br \/>\n1b) Generovanie a charakteriz\u00e1cia \u0161pecifick\u00fdch bunkov\u00fdch l\u00edni\u00ed<br \/>\n1c) \u0160t\u00fadium \u00falohy M6 \/IGF2R a u AR v T-bunkovej migr\u00e1cii<br \/>\n1d) \u0160t\u00fadium \u00falohy M6 \/IGF2R a u AR v aktiv\u00e1cii latentn\u00e9ho TGF-beta<br \/>\n1e) \u0160t\u00fadium regul\u00e1cie M6 \/IGF2R-u AR komplexu a asociovan\u00fdch partnerov \u2013 Fenotypiz\u00e1cia a funk\u010dn\u00e1 anal\u00fdza M6P\/IGF2R-uPAR-pozit\u00edvneho T bunkov\u00e9ho subsetu<\/p>\n<p>Hlavn\u00fd cie\u013e #2: Vroden\u00fd imunitn\u00fd syst\u00e9m \u2013 \u0161t\u00fadium plazminog\u00e9nov\u00e9ho syst\u00e9mu pri eferocyt\u00f3ze prostredn\u00edctvom makrof\u00e1gov: v tejto \u010dasti projektu budeme:<br \/>\n(i) detailne popisova\u0165 molekul\u00e1rny mechanizmus eferocyt\u00f3zy z\u00e1vislej od plazminog\u00e9nu;<br \/>\n(ii) charakterizova\u0165 fyziologick\u00fa d\u00f4le\u017eitos\u0165 tohto mechanizmu v naviazan\u00ed na zodpovedaj\u00facu subpopul\u00e1ciu makrof\u00e1gov;<br \/>\n(iii) produkova molekul\u00e1rne n\u00e1stroje vhodn\u00e9 na farmakologick\u00fa \u00fapravu eferocyt\u00f3zy<\/p>\n<p>\u0160pecifick\u00e9 ciele:<br \/>\n2a) Identifik\u00e1cia plazminog\u00e9nov\u00fdch receptorov na apoptotick\u00fdch bunk\u00e1ch<br \/>\n2b) Profil\u00e1cia expresie M6 \/IGF2R pri diferenci\u00e1cii makrof\u00e1gov \u2013 funk\u010dn\u00e1 charakteriz\u00e1cia M6 \/IGF2R-pozit\u00edvneho makrof\u00e1goveho subsetu<br \/>\n2c) Charakteriz\u00e1cia molekul\u00e1rnych determinantov zapojen\u00fdch do v\u00e4zby plazminog\u00e9nu na laktofer\u00edn<br \/>\n2d) In vitro modul\u00e1cia eferocyt\u00f3zy cez M6 \/IGF2R<br \/>\n2e) Identifik\u00e1cia partnerov pre M6 \/IGF2R, u AR a plazminog\u00e9n v makrof\u00e1goch<\/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:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30657605\")'><img decoding=\"async\" class=\"alignnone wp-image-1110\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/logo-JLeukocBiol.png\" alt=\"SciRep\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\">Ohradanova-Repic A, Machacek C, Donner C, Muhlgrabner V, Petrovcikova E, <strong>Zahradn\u00edkov\u00e1 A Jr<\/strong>, Vicikova K, Horejsi V, Stockinger H, Leksa V (2019): <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30657605\")'>The mannose 6-phosphate\/insulin-like growth factor 2 receptor mediates plasminogen-induced efferocytosisy<\/a>. <i>J Leukoc Biol.<\/i> 105: 519-530, doi: 10.1002\/JLB.1AB0417-160RR.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>Regul\u00e1cia pericelul\u00e1rnej proteol\u00fdzy: od molekul\u00e1rnych mechanizmov k nov\u00fdm subsetom imunitn\u00fdch buniek a terapeutick\u00fdm n\u00e1strojom (PPIS) &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Nasp\u00e4\u0165 Koordin\u00e1tor: Vladim\u00edr Leksa Ved\u00faci projektu za BMC SAV: Alexandra&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/apvv-16-0452\/\">\u010d\u00edta\u0165 \u010falej &raquo;<\/a><\/span><\/p>\n","protected":false},"author":2,"featured_media":0,"parent":117,"menu_order":80,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/542"}],"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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/comments?post=542"}],"version-history":[{"count":10,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/542\/revisions"}],"predecessor-version":[{"id":2555,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/542\/revisions\/2555"}],"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=542"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}