Nthawi ya Imfa: Zamakono Zatsopano Zofunikira Kuti Zikhale Zolondola Kwambiri

Kwa ofufuza omwe amaphunzira za neurodegeneration, kusowa kwa chidziwitso cha "nthawi ya kufa" kwa ma neuron kumapangitsa kuti zikhale zovuta kudziwa zomwe zimayambitsa kufa kwa maselo ndikuwunika mankhwala omwe angapulumutse maselo okalamba kuti asafe.              

Tsopano, ofufuza a Gladstone Institutes apanga ukadaulo watsopano womwe umawalola kutsata masauzande a maselo nthawi imodzi ndikuzindikira nthawi yeniyeni ya kufa kwa selo lililonse m'gululo. Gululo linasonyeza, mu pepala lofalitsidwa mu nyuzipepala ya Nature Communications, kuti njirayo imagwira ntchito mu makoswe ndi maselo aumunthu komanso mkati mwa zebrafish yamoyo, ndipo ingagwiritsidwe ntchito kutsatira maselo kwa nthawi ya masabata mpaka miyezi.

"Kupeza nthawi yeniyeni ya imfa n'kofunika kwambiri kuti athetse zomwe zimayambitsa ndi zotsatira za matenda a neurodegenerative," akutero Steve Finkbeiner, MD, PhD, mkulu wa Center for Systems and Therapeutics ku Gladstone ndi wolemba wamkulu wa maphunziro onse atsopano. "Zimatithandiza kudziwa kuti ndi zinthu ziti zomwe zimayambitsa kufa kwa maselo, zomwe zimangochitika mwadzidzidzi, komanso zomwe zitha kukhala njira zomwe zimachedwetsa kufa."

Mu pepala lina lofalitsidwa m'magazini ya Science Advances, ofufuzawo anaphatikiza teknoloji ya sensa ya selo ndi njira yophunzirira makina, kuphunzitsa makompyuta momwe angasiyanitsire maselo amoyo ndi akufa maulendo 100 mofulumira komanso molondola kuposa munthu.

"Zinawatengera miyezi ophunzira aku koleji kusanthula deta yamtunduwu ndi dzanja, ndipo dongosolo lathu latsopano limakhala nthawi yomweyo - limayenda mwachangu kuposa momwe tingathere zithunzi zatsopano pamamicroscope," akutero Jeremy Linsley, PhD, mtsogoleri wa pulogalamu yasayansi ku Finkbeiner's. lab ndi wolemba woyamba wa mapepala onse atsopano.

Kuphunzitsa Zanzeru Zatsopano Za Sensor Yakale

Maselo akamwalira—kaya ndi chifukwa chotani kapena kagwiridwe kanji—m’kupita kwa nthaŵi amagaŵanika ndipo nembanemba yake imawonongeka. Koma kunyonyotsoka kumeneku kumatenga nthaŵi, kumapangitsa kukhala kovuta kwa asayansi kusiyanitsa pakati pa maselo amene anasiya kugwira ntchito kwa nthaŵi yaitali, amene akudwala ndi kufa, ndi amene ali athanzi.

Ofufuza nthawi zambiri amagwiritsa ntchito ma tag a fulorosenti kapena utoto kuti atsatire maselo odwala ndi maikulosikopu pakapita nthawi ndikuyesera kudziwa komwe ali mkati mwa njira yoipayi. Mitundu yambiri yowonetsera, madontho, ndi zolemba zapangidwa kuti zisiyanitse maselo akufa kale ndi omwe adakali ndi moyo, koma nthawi zambiri amagwira ntchito kwa nthawi yochepa asanazime ndipo amatha kukhala poizoni ku maselo akagwiritsidwa ntchito.

Linsley anati: “Tinkafunadi chizindikiro chimene chimakhala kwa moyo wonse wa selo, osati kwa maola ochepa chabe, kenako n’kupereka chizindikiro chomveka bwino pakangopita mphindi yeniyeni imene selo yafa.

Linsley, Finkbeiner, ndi anzawo adasankha masensa a calcium, omwe adapangidwa kuti azitsata kuchuluka kwa kashiamu mkati mwa cell. Selo likafa ndipo nembanemba zake zimachucha, chotsatira chake n’chakuti kashiamu imathamangira mu selo yotchedwa cytosol yamadzi, imene nthawi zambiri imakhala ndi kashiamu wochepa kwambiri.

Chifukwa chake, Linsley adapanga ma sensa a calcium kuti azikhala mu cytosol, pomwe amatha kuphulika pokhapokha ngati ma calcium awonjezeka kufika pamlingo wowonetsa kufa kwa cell. Masensa atsopano, omwe amadziwika kuti genetically encoded death indicator (GEDI, amatchulidwa ngati Jedi mu Star Wars), akhoza kuikidwa mumtundu uliwonse wa selo ndikuwonetsa kuti selo liri lamoyo kapena lakufa pa moyo wonse wa selo.

Pofuna kuyesa kugwiritsa ntchito masensa opangidwanso, gululo linayika magulu akuluakulu a neurons-aliyense ali ndi GEDI-pansi pa microscope. Pambuyo poyang'ana maselo opitirira miliyoni, nthawi zina amatha kudwala matenda a neurodegeneration ndi ena omwe amapezeka ndi mankhwala oopsa, ofufuzawo adapeza kuti sensa ya GEDI inali yolondola kwambiri kuposa zizindikiro zina za imfa ya maselo: panalibe vuto limodzi limene sensa inalipo. adayatsidwa ndipo selo linakhalabe ndi moyo. Komanso, kuwonjezera pa kulondola kumeneko, GEDI inawonekanso kuti imazindikira kufa kwa maselo pa nthawi yoyamba kusiyana ndi njira zam'mbuyomu-pafupi ndi "popanda kubwerera" kwa selo kufa.

“Izi zimakulolani kuti mulekanitse maselo amoyo ndi akufa m’njira imene simunathekepo,” akutero Linsley.

Kuzindikira Imfa Yapamwamba

Linsley adatchulapo za GEDI kwa mchimwene wake - Drew Linsley, PhD, wothandizira pulofesa ku Brown University yemwe amagwiritsa ntchito luntha lochita kupanga pazambiri zazikulu zamoyo. Mchimwene wake adanena kuti ochita kafukufukuwo agwiritse ntchito kachipangizo, pamodzi ndi njira yophunzirira makina, kuphunzitsa makompyuta kuti azindikire maselo amoyo ndi akufa a ubongo pogwiritsa ntchito mawonekedwe a selo.

Gululo lidaphatikiza zotsatira kuchokera ku sensa yatsopano yokhala ndi data yofananira ya fluorescence pamanyuroni omwewo, ndipo adaphunzitsa makina apakompyuta, otchedwa BO-CNN, kuti azindikire mawonekedwe amtundu wa fluorescence okhudzana ndi momwe maselo akufa amawonekera. Chitsanzocho, abale a Linsley anasonyeza, chinali 96 peresenti yolondola ndi yabwino kuposa zomwe owona aumunthu angakhoze kuchita, ndipo anali mofulumira kuposa 100 kuposa njira zakale zosiyanitsira maselo amoyo ndi akufa.

“Kwa mitundu ina ya maselo, n’kovuta kwambiri kuti munthu azindikire ngati selo lili lamoyo kapena lafa—koma chitsanzo chathu cha kompyuta, pophunzira kuchokera ku GEDI, chinatha kusiyanitsa malinga ndi mbali za zithunzi zimene sitinali kuzidziŵa poyamba. zinali zothandiza kusiyanitsa maselo amoyo ndi akufa,” akutero Jeremy Linsley.

Onse a GEDI ndi BO-CNN tsopano adzalola ochita kafukufuku kuti azichita maphunziro atsopano, apamwamba kwambiri kuti apeze nthawi ndi kumene maselo a ubongo amafera-mapeto ofunikira kwambiri pa matenda ena ofunika kwambiri. Amathanso kuyang'ana mankhwala kuti athe kuchedwetsa kapena kupewa kufa kwa maselo m'matenda a neurodegenerative. Kapena, ngati ali ndi khansa, amatha kufufuza mankhwala omwe amathandizira kufa kwa maselo omwe ali ndi matenda.

Finkbeiner anati: “Matekinoloje amenewa ndi osintha masewera kuti tithe kumvetsa kumene, liti, ndiponso chifukwa chake imfa imachitikira m’maselo. "Kwa nthawi yoyamba, titha kugwiritsa ntchito liwiro ndi sikelo yoperekedwa ndi kupita patsogolo kwa ma microscopy mothandizidwa ndi maloboti kuti tizindikire molondola kufa kwa maselo, ndikuchita izi nthawi isanakwane imfa. Tikukhulupirira kuti izi zitha kubweretsa njira zochiritsira zenizeni zamatenda ambiri a neurodegenerative omwe sanachiritsidwe mpaka pano. ”