Kubaphandi abafunda nge-neurodegeneration, oku kunqongophala “kwexesha lokufa” elichanekileyo leeneurons kwenza kube nzima ukucacisa ukuba zeziphi izinto ezikhokelela ekufeni kweeseli kunye nokuhlola amachiza anokusindisa iiseli ezalupheleyo ekufeni.
Ngoku, abaphandi bamaZiko eGladstone baphuhlise itekhnoloji entsha ebavumela ukuba balandele amawaka eeseli ngexesha kwaye bamisele umzuzu ochanekileyo wokufa kwayo nayiphi na iseli kwiqela. Iqela libonise, kwiphepha elipapashwe kwijenali yezoNxibelelwano lweNdalo, ukuba le ndlela isebenza kwii-rodent kunye neeseli zomntu kunye nakwi-zebrafish ephilayo, kwaye ingasetyenziselwa ukulandela iiseli kwithuba leeveki ukuya kwiinyanga.
"Ukufumana ixesha elichanekileyo lokufa kubaluleke kakhulu ekuvuleni imbangela kunye nefuthe kwizifo ze-neurodeergenerative," kusho uSteve Finkbeiner, MD, PhD, umlawuli weZiko leeNkqubo kunye neTherapeutics eGladstone kunye nombhali ophezulu wazo zombini izifundo ezitsha. "Isivumela ukuba sifumanise ukuba zeziphi izinto ezibangela ngokuthe ngqo ukufa kweeseli, ezinokuthi zenzeke, kwaye ezinokuthi zijongane neendlela ezilibazisa ukufa."
Kwiphepha elingumhlobo elipapashwe kwiphephancwadi iScience Advances , abaphandi badibanisa iteknoloji yesivamvo seseli kunye nendlela yokufunda ngomatshini, befundisa ikhompyutha indlela yokwahlula iiseli eziphilayo nezifileyo kangangezihlandlo ezili-100 ngokukhawuleza nangokuchaneka ngakumbi kunomntu.
"Kwathatha iinyanga zabafundi beekholeji ukuhlalutya olu hlobo lwedatha ngesandla, kwaye inkqubo yethu entsha iphantse yakhawuleza-ihamba ngokukhawuleza kunokuba sinokufumana imifanekiso emitsha kwi-microscope," utsho uJeremy Linsley, PhD, inkokeli yenkqubo yesayensi kwiFinkbeiner's. elebhu kunye nombhali wokuqala wawo omabini amaphepha amatsha.
Ukufundisa iSensor endala amaqhinga amatsha
Xa iiseli zisifa—enoba yintoni na unobangela okanye isixhobo—ekugqibeleni ziyaqhekeka yaye inwebu yazo iyawohloka. Kodwa le nkqubo yokuwohloka kwemilinganiselo ithatha ixesha, nto leyo eyenza kube nzima ngezazinzulu ukwahlula phakathi kweeseli ekudala zayeka ukusebenza, ezo zigulayo nezifayo, nezo zisempilweni.
Abaphandi bahlala besebenzisa iithegi ze-fluorescent okanye idayi ukulandela iiseli ezigulayo nge-microscope ngokuhamba kwexesha kwaye bazame ukufumanisa ukuba bakuphi kule nkqubo yokuthotywa. Iidayi ezininzi ezibonisayo, amabala, kunye neelebhile ziye zaphuhliswa ukwahlula iiseli esele zifile kwezo zisaphila, kodwa zihlala zisebenza ixesha elifutshane ngaphambi kokuba ziphele kwaye zinokuba yingozi kwiiseli xa zisetyenziswa.
ULinsley uthi: “Besifuna isalathisi esihlala ubomi bonke beseli—kungekhona nje iiyure ezimbalwa— size sichaze ngokucacileyo emva kokuba iseli ifile.
U-Linsley, uFinkbeiner, kunye noogxa babo badibanisa i-calcium sensors, eyenzelwe ukulandelela amanqanaba e-calcium ngaphakathi kweseli. Njengoko iseli isifa yaye inwebu yayo ivuza, esinye isiphumo sesokuba i<em>calcium igxalathelana ukuya kwi<em>cytosol enamanzi eseli, edla ngokuba nomlinganiselo ophantsi we<em>calcium.
Ke, u-Linsley wenza iisenso ze-calcium ukuba zihlale kwi-cytosol, apho zaziya ku-fluoresce kuphela xa amanqanaba e-calcium enyuka ukuya kwinqanaba elibonisa ukufa kweeseli. Izinzwa ezintsha, ezaziwa njengesalathisi sokufa esifakwe kwimfuza (i-GEDI, ebizwa njenge-Jedi kwi-Star Wars), inokufakwa kulo naluphi na uhlobo lweseli kunye nomqondiso wokuba iseli iyaphila okanye ifile kubomi bonke beseli.
Ukuvavanya ukusetyenziswa kweenzwa ezihlaziyiweyo, iqela labeka amaqela amakhulu e-neurons-ngalinye liqukethe i-GEDI-phantsi kwe-microscope. Emva kokubona iiseli ezingaphezulu kwesigidi, kwezinye iimeko ezithambekele kwi-neurodegeneration kwaye kwezinye zichaneke kwiikhompawundi ezinetyhefu, abaphandi bafumanisa ukuba i-GEDI sensor yayichaneke kakhulu kunezinye izalathi zokufa kweeseli: kwakungekho nalinye ityala apho inzwa yasebenza kwaye iseli yahlala iphila. Ngaphezu koko, ngaphezu koko kuchaneka, i-GEDI nayo ibonakala ibona ukufa kweeseli kwinqanaba langaphambili kuneendlela zangaphambili-kufuphi "kwindawo yokungabuyi" yokufa kweeseli.
“Oku kukuvumela ukuba wahlule iiseli eziphilayo nezifileyo ngendlela engazange yenzeke ngaphambili,” utsho uLinsley.
Ukufunyanwa koKufa okungaphaya komntu
U-Linsley ukhankanye i-GEDI kumntakwabo-Drew Linsley, PhD, unjingalwazi oncedisayo kwiYunivesithi yaseBrown ogxile ekusebenziseni ubukrelekrele bokwenziwa kwidatha enkulu yebhayoloji. Umntakwabo ucebise ukuba abaphandi basebenzise inzwa, kunye nendlela yokufunda umatshini, ukufundisa inkqubo yekhompyuter ukuqaphela iiseli zengqondo eziphilileyo nezifileyo ezisekelwe kuphela kwimo yeseli.
Iqela lidibanise iziphumo ezivela kwi-sensor entsha kunye nedatha ye-fluorescence esemgangathweni kwii-neuron ezifanayo, kwaye bafundisa imodeli yekhompyuter, ebizwa ngokuba yi-BO-CNN, ukuqaphela iipateni ze-fluorescence ezihambelana nokuba zikhangeleka njani iiseli ezifayo. Imodeli, abazalwana bakaLinsley babonisa, ipesenti ye-96 ichanekile kwaye ingcono kunokuba abantu ababukeleyo bangayenza, kwaye yayingaphezu kwe-100 ngokukhawuleza kuneendlela zangaphambili zokwahlula iiseli eziphilayo nezifileyo.
Kwezinye iintlobo zeeseli, kunzima kakhulu ukuba umntu aqonde ukuba iseli iyaphila okanye ifile—kodwa imodeli yethu yekhompyuter, ngokufunda kwiGEDI, ikwazile ukuzohlula ngokusekwe kumacandelo emifanekiso ebesingayazi ngaphambili. zaziluncedo ekwahluleni iiseli eziphilayo nezifileyo,” utsho uJeremy Linsley.
Bobabini i-GEDI kunye ne-BO-CNN ngoku baya kuvumela abaphandi ukuba baqhube izifundo ezintsha, eziphezulu zokufumana ukuba nini kwaye phi iiseli zengqondo zifa-isiphelo esibaluleke kakhulu kwezinye zezifo ezibaluleke kakhulu. Basenokuvavanya amachiza ngokukwazi kwabo ukulibazisa okanye ukunqanda ukufa kweeseli kwizifo ze-neurodeergenerative. Okanye, kwimeko yomhlaza, banokukhangela amayeza akhawulezisa ukufa kweeseli ezigulayo.
UFinkbeiner uthi: “Obu bugcisa butshintsha indlela esikwazi ngayo ukuqonda ukuba kuphi, nini, kwaye kutheni ukufa kwenzeka kwiiseli. "Okokuqala ngqa, sinokusebenzisa isantya kunye nesikali esibonelelwe yinkqubela phambili yerobhothi encediswa ngemakroskopu ukubona ngokuchanekileyo ngakumbi ukufa kweeseli, kwaye sikwenze oko kwangaphambi kwexesha lokufa. Siyathemba ukuba oku kunokukhokelela kunyango oluthe ngqo kwizifo ezininzi ze-neurodeergenerative ezingekanyangeki ukuza kuthi ga ngoku. ”
INTO ONOKUYITHATHA KWELI NQAKU:
- The team showed, in a paper published in the journal Nature Communications, that the approach works in rodent and human cells as well as within live zebrafish, and can be used to follow the cells over a period of weeks to months.
- Kwiphepha elingumhlobo elipapashwe kwiphephancwadi iScience Advances , abaphandi badibanisa iteknoloji yesivamvo seseli kunye nendlela yokufunda ngomatshini, befundisa ikhompyutha indlela yokwahlula iiseli eziphilayo nezifileyo kangangezihlandlo ezili-100 ngokukhawuleza nangokuchaneka ngakumbi kunomntu.
- Now, researchers at Gladstone Institutes have developed a new technology that lets them track thousands of cells at a time and determine the precise moment of death for any cell in the group.
