Ingantacciyar maganin blister don EBS
Mataki na farko a cikin haɓaka sabuwar hanyar da za a bi da blisters na EBS ta amfani da abubuwan da ke canza DNA na ƙwayoyin fata don inganta ingancin rayuwa ga yara da manya masu fama da wannan yanayin.
Farfesa John Connelly yana aiki a Jami'ar Queen Mary, London, UK akan wannan aikin don nazarin warkaswa na EBS a cikin dakin gwaje-gwaje. Za a gwada wani kwamiti na yuwuwar jiyya akan ƙwayoyin fata da aka girma a cikin jita-jita a cikin dakin gwaje-gwaje don gano waɗanda za su iya canza tsarin DNA kuma za a iya ci gaba zuwa ƙarin gwaji. Kara karantawa game da aikin daga masu haɗin gwiwarmu da kuma shafin mai binciken mu.
Game da kudaden mu
| Jagoran Bincike | Farfesa John Connelly |
| Institution | Cibiyar Blizard, Jami'ar Maryamu Maryamu na London, Birtaniya |
| Nau'in EB | EBS |
| Hanyar haƙuri | A'a |
| Adadin kuɗi | £199,752 (haɗin gwiwa tare da Action Medical Research for Children) |
| Tsawon aikin | 3 shekaru |
| Fara kwanan wata | 1 Satumba 2023 |
| DEBRA ID na ciki | GR000021 |
Bayanan aikin
Masu bincike sun gano cewa canje-canjen kwayoyin halitta na EBS suna canza samar da sunadaran da ke yin tsakiya a kowace tantanin halitta. Nucleus wani akwati ne na chromosomes na tantanin halitta kuma ya lalace a cikin waɗannan kwayoyin halitta - yana kama da siffar da ba daidai ba a karkashin na'urar hangen nesa. Wannan da alama yana sa sel su zama kamar suna lalacewa koyaushe. Ba su iya ba da amsa yadda ya kamata ta hanyar yin sunadaran da ake buƙata lokacin da fata ta sami rauni ko kumburi. A saman raunin inji/tsari na fatar EB, wannan yuwuwar rage ikon gyara raunuka za a iya niyya don inganta alamun.
A cikin shekarar farko na wannan aikin, masu bincike sun haɓaka ƙwayoyin fata daga mutanen da ke da EBS da kuma canza ƙwayoyin fata waɗanda suka riga sun girma sosai a cikin dakin gwaje-gwaje don sa su zama kamar sel daga mutanen da ke da EBS. Sun yi amfani da waɗannan sel don yin ƙirar warkar da rauni ta ganin tsawon lokacin da ake ɗaukar su don rufe ɓarna a cikin sel masu girma. Nazarin farko sun gano bambance-bambance a cikin sel EBS idan aka kwatanta da sel na al'ada kuma mataki na gaba na aikin zai ga idan jiyya na iya juyar da waɗannan bambance-bambancen kuma inganta aikin waɗannan ƙwayoyin cuta a cikin samfurin warkar da rauni.
Masu bincike sun gabatar da aikin su a matsayin Poster a watan Afrilu 2024.
Jagoran bincike:
Farfesa John Connelly jagora ne a fannin fasahar fata da kuma sanin injinan salula. dakin gwaje-gwajensa yana amfani da kewayon samfuran in vitro don rarraba hanyoyin da ƙwayoyin fata ke ganewa da amsa alamun injina da kuma rawar waɗannan sigina a cikin lafiyar fata da cututtuka.
Masu bincike:
Farfesa David Kelall kwararre ne kan cututtukan fata na kwayoyin halittar dan adam. dakin gwaje-gwajensa yana amfani da hanyoyin nazarin halittu da kwayoyin halitta don bincikar cututtukan fata na ɗan adam.
Farfesa Julien Gautrot kwararre ne a fannin nazarin halittu, kuma dakin bincikensa yana samar da sabbin kayan aiki don isar da kwayoyin halitta da kwayoyin halitta. Bugu da ƙari, yana da ƙwarewa a fasaha na gaba-on-chip, kuma ƙungiyarsa ta ƙera sababbin tsarin don ƙirar fata da aikin injiniya.
Haɗin kai:
Farfesa Adrian Heagerty, Jami'ar Birmingham.
"Wadannan karatun za su kasance mataki na farko na haɓaka sabon tsarin kula da EBS kuma za su kafa tushe don fassarar waɗannan hanyoyin kwantar da hankali zuwa fa'idar haƙuri."
– Farfesa John Connelly
Sunan baiwa: Yin niyya ka'idodin tsarin halittar halittu a cikin epidermolysis bullosa simplex
Epidermolysis bullosa simplex (EBS) cuta ce da ba kasafai ba ce ta kwayoyin halittar fata da ke haifar da maye gurbin keratin a cikin epidermis, kuma daga haihuwa yana haifar da fata mai rauni mai saurin kamuwa da kumburi mai radadi. A halin yanzu babu magani ga EBS, kuma sabbin hanyoyin kwantar da hankali don gyara tsananin cutar suna da yuwuwar samar da manyan fa'idodi da inganta rayuwar yara da iyalai masu fama da wannan cuta. Nazarin kwanan nan na dakin gwaje-gwajenmu sun gano sauye-sauye daban-daban kuma a cikin tsakiya na sel tare da maye gurbin keratin, wanda ya kai mu ga hasashe cewa tsarin nukiliya da ƙungiyar DNA suna ba da gudummawa ga alamun da tsanani na EBS. Bugu da ƙari, muna ba da shawarar cewa amfani da mahadi masu wanzuwa waɗanda aka sani da 'masu hanawa na epigenetic', waɗanda ke tsara marufi na DNA a cikin tsakiya, suna da yuwuwar gyara tsarin nukiliya a cikin keratinocytes na EBS da haɓaka gyaran blister. Don haka wannan aikin yana da nufin siffanta canjin matakin ƙwayoyin cuta a cikin ƙungiyar nukiliya ta haifar da maye gurbi na EBS da kuma aiwatar da gwajin farko na zaɓaɓɓen kwamiti na masu hana epigenetic don ganin ko za su iya inganta warkar da raunuka da ƙuduri a cikin dakin gwaje-gwaje. Waɗannan karatun za su zama mataki na farko na haɓaka sabon tsarin kula da EBS kuma zai sa aikin fassara waɗannan hanyoyin kwantar da hankali zuwa fa'idar haƙuri. Matakai na gaba da ke biye da wannan binciken shine zabar magunguna mafi inganci kuma a kai su gaba zuwa ƙarin gwaji da gwaji na asibiti.
Epidermolysis bullosa simplex (EBS) cuta ce ta fata da ba kasafai take fitowa ba ta hanyar maye gurbi a cikin keratins na epidermis. Yayin da gabaɗayan tasirin injina na waɗannan maye gurbi na keratin akan raunin fata da kumburin fata sun kafu sosai, ba a san tasirin tasirin siginar siginar siginar ƙwayoyin ƙwayoyin cuta na cikin salula da martanin kumburi ba. Wannan aikin don haka yana nufin rarraba tasirin EBS-saukar maye gurbi akan keratinocyte danniya martani da kumburi.
Har zuwa yau, mun ƙirƙiri sababbin layin salula na keratinocyte waɗanda ke bayyana keratin 14 (K14) tare da sauye-sauye daban-daban da aka sani don haifar da EBS, kuma mun lura da canje-canje masu ban mamaki a cikin tsakiya na waɗannan kwayoyin halitta, wanda ke nuna ƙananan ƙwayoyin cuta da maras kyau tare da canza yanayin sunadaran ambulan na nukiliya. Mun kuma gano cewa waɗannan sel sun ƙara yawan magana na asali na sunadaran amsawar damuwa kuma sun kasa daidaita waɗannan sunadaran don mayar da martani ga matsalolin waje, irin su ultraviolet radiation. Ƙarin bayanin bayanan kwayoyin halitta ya buɗe hanyoyin haɗin kai zuwa rashin haɓakar haɓakar haɓakar haɓakar haɓakar haɓakar haɓakar haɓakar haɓakar haɓakar haɓakar cytokine a cikin keratinocytes na EBS. Tare, waɗannan binciken suna nuni ga yuwuwar hanyar sigina wanda nakasar nukiliya a cikin ƙwayoyin EBS ke haifar da ƙayyadaddun bayanan sunadaran amsa damuwa da ƙarancin siginar kumburi. Wadannan binciken sun kara nuna cewa, ban da kasancewa mai rauni na injiniya, epidermis na marasa lafiya na EBS na iya samun rashin ƙarfi don amsa damuwa da gyaran nama. Don haka, niyya na wannan hanyar na iya zama wata dabarar da za ta iya inganta warkar da raunuka a cikin marasa lafiya na EBS, amma ana buƙatar ƙarin bincike don tabbatar da waɗannan hanyoyin.
A cikin bincikenmu na baya, mun lura cewa keratinocytes tare da maye gurbi masu haifar da EBS sun nuna canjin yanayin lamina na nukiliya, waɗanda ke da mahimmancin tsarin tsarin nukiliya da ƙungiyar kwayoyin halitta. Wadannan binciken sun kai mu ga hasashe cewa EBS keratinocytes sun canza tsarin gine-ginen nukiliya wanda ke tasiri ga bayyanar cututtuka da cututtukan cututtuka. Babban manufar aikin da aka gabatar shine don tantance sakamakon EBS mai haifar da maye gurbi na keratin akan gine-ginen nukiliya da ka'idojin kwayoyin halitta. Bugu da ƙari, mun yi niyyar bincika ko daidaita yanayin magana tare da masu hana epigenetic.
Shirin aikin ya ƙunshi manyan manufofi/manufofi guda uku:
1. Kafa samfurin HSE na 3D na EBS tare da sarrafa damuwa na inji.
2. Yi la'akari da panel na masu hana epigenetic don inganta gyaran raunuka a cikin 3D model na EBS.
3. Bincika tsarin epigenetic da tsarin tsarin tsarin aikin don zaɓin masu hanawa.
An ƙara sabon maƙasudi na huɗu a cikin aikin bayan binciken da aka yi kwanan nan cewa nakasar nukiliya da rashin ƙarfi sun shiga cikin kunna hanyar cGAS-STING, wanda ke jin DNA na cytosolic kuma yana haifar da bayyanar cututtukan ƙwayoyin cuta, kamar nau'in interferon I:
4. Bincika sauye-sauye masu kumburi da damuwa a cikin EBS keratinocytes.
(Daga rahoton ci gaba na Yuli 2025.)
Babban manufar wannan aikin shine fahimtar yadda epidermolysis bullosa simplex (EBS) ke rinjayar maganganun kwayoyin halitta a cikin keratinocytes da kuma gano ko wani nau'i na magungunan da aka sani da 'epigenetic inhibitors' zai iya taimakawa wajen gyara maganganun kwayoyin halitta da kuma taimakawa wajen inganta warkarwa a cikin EBS. Ƙayyadaddun manufofin aikin shine a fara bayyana yadda ake canza tsarin kwayoyin halitta a cikin sel na EBS da kuma ƙayyade rawar abubuwan epigenetic, wanda ke nufin yadda aka tattara DNA a cikin tsakiya. Sa'an nan kuma mu yi shirin bincikar yadda jiyya tare da panel na daban-daban masu hana epigenetic ke shafar warkar da raunuka da kuma tsarin nama na 3D ta amfani da ƙirar fata na injiniya a cikin dakin gwaje-gwaje.
A cikin shekarar farko na aikin, mun mai da hankali kan kafa mahimman kayan aikin da inganta ka'idojin gwaji don gudanar da waɗannan karatun. Wannan aikin ya haɗa da injiniyan sabbin layin keratinocyte tare da maye gurbin keratin daban-daban guda biyu, waɗanda aka sani don haifar da EBS, da kuma abubuwan da suka dace da tsarin halittarsu. Yanzu mun tabbatar da cewa waɗannan sel suna bayyana matakan kamanni na mutant da keratins na yau da kullun da kuma gabatarwar keratin na mutant yana haifar da samuwar keratin aggregates, kamar yadda ake gani a cikin fata masu haƙuri da ƙwayoyin al'ada. Mun kuma sami sabbin layukan tantanin halitta waɗanda marasa lafiya suka samu tare da madaidaitan maye gurbi da inganta yanayin al'adun su, kuma mun kafa ƙididdiga don nazarin ƙulli rauni da ƙirar al'adun 3D ta amfani da duk waɗannan ƙwayoyin.
Kwanan nan mun fara kwatanta tasirin keratin maye gurbi a cikin layin da aka yi amfani da su akan abubuwan epigenetic a cikin keratinocytes. Nazarin farko ya nuna cewa maye gurbi na EBS yana haifar da manyan canje-canje a cikin tsari da tsari na tsakiya a cikin keratinocytes. Wadannan binciken sun ba da gudummawa mai kyau ga manufar farko na aikin, suna nuna yanayin yanayin EBS keratinocytes. Tare da ingantattun yanayin al'adu da ƙididdigar da aka ambata a sama, yanzu an sanya mu da kyau don bincika tasirin waɗannan sauye-sauye na epigenetic akan aikin tantanin halitta da nama da kuma ko za a iya gyara su ta hanyar masu hana epigenetic don inganta raunin rauni a mataki na gaba na aikin. (Daga rahoton ci gaba na 2024.)