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PhD: inganta gyaran fata a cikin JEB

Wannan aikin zai horar da wani sabon masanin kimiyya wanda ya kware a binciken EB yayin da suke samun digiri na uku ta hanyar nazarin hanyoyin rage alamun EB a matakin salula.

Hoton Dr Rognoni.

Dr Rognoni yana aiki a Cibiyar Blizard (QMUL) kuma zai kula da ɗalibin PhD don aiwatar da wannan aikin akan ƙwayoyin fata na JEB. Abubuwan da suka riga sun wanzu don dakatar da lalacewar takamaiman furotin, wanda ake kira integrin αvβ6 (alpha V beta shida), wanda ya bayyana yana ba da gudummawa ga kumburi, tabo da jinkirin warkar da rauni a cikin fata na EB. Kwayoyin fata tare da canjin kwayoyin halitta wanda ke haifar da JEB za su girma a cikin yadudduka a matsayin samfurin fata na JEB, don haka ana iya gwada waɗannan abubuwa don ganin ko sun rage kumburi da inganta gyaran fata. Sakamakon zai iya zama dacewa ga sauran nau'ikan EB kuma, saboda integrin αvβ6 yana cikin kowane nau'in EB.

 

Game da kudaden mu

 

Jagoran Bincike Dr Emanuel Rognoni
Institution Jami'ar Sarauniya Mary ta London, Kwalejin Magunguna da Dentistry, Cibiyar Blizard
Nau'in EB JEB
Hanyar haƙuri A'a
Adadin kuɗi £139,962
Tsawon aikin Daliban PhD ba na asibiti ba - shekaru 4
Fara kwanan wata 1 May 2024
DEBRA ID na ciki GR000049

 

Bayanan aikin

Domin 2025.

Jagoran bincike:

Dr Emanuel Rognoni babban malami ne a Cibiyar Blizard. A lokacin da PhD ya mayar da hankali kan EB subtype Kindler Syndrome inda ya bayyana wani sabon aiki na integrin daure protein Kindlin-1 don epithelial stem cell homeostasis ta inganta αvβ6 integrin-mediated canza girma factor-β (TGFβ) kunnawa da epithelial Wnt sigina. A lokacin postdoc ɗinsa ya ƙara ƙwarewa a cikin binciken fata, yana bincikar yadda ƙungiyoyin fibroblast dermal daban-daban ke tsarawa da tasiri juna yayin haɓakawa da warkar da rauni a cikin Lab ɗin Farfesa Fiona Watt (KCL). Yin amfani da fasahohin jeri-fadi na genome, sabbin dandamali na al'adun 2D / 3D da samfuran transgenic / cuta, ƙungiyarsa a QMUL yanzu tana buɗe hanyoyin ƙwayoyin ƙwayoyin cuta da abubuwan da ke tattare da fibroblast iri-iri a cikin lafiyar fata, sabuntawa da cuta.

Masu bincike:

Dokta Matthew Caley babban malami ne a cikin Halittar Halittu a Cibiyar Blizard tare da gogewa fiye da shekaru goma a cikin binciken fata, ilimin halitta na matrix da kuma samar da samfuran fata a cikin vitro. Yana aiki a cikin al'ummomin binciken fata na Biritaniya da Turai, memba na kungiyar British Society for Investigative Dermatology (BSID) da kuma wanda ya kafa cibiyar sadarwa ta Skin Microbiome in Healthy Aging (SMiHA). Ƙungiyarsa tana amfani da nau'ikan fata don fahimtar ilimin kwayoyin halitta na tsufa na fata, cututtukan fata da ba kasafai ba da kuma ciwon daji na fata. Ya mayar da hankali na musamman kan laminin 332 da kuma yadda wannan furotin ya wuce kawai gina jiki.

Farfesa John Marshall Farfesa ne na Tumor Biology wanda bincikensa ya mayar da hankali kan aikin masu karɓar mannewar cell, integrins, a cikin mamayewar ƙwayoyin tumo tare da wallafe-wallafe sama da 130. Shi babban ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararren ƙwararru ne na ƙwanƙwasa ƙwanƙwasa αvβ6 wanda ke haɓakawa sosai yayin gyaran nama a cikin raunuka na yau da kullun da ciwon daji. Bincikensa ya ƙunshi haɗin gwiwar masana'antu da yawa da gwaji na asibiti.

"Manufarmu ita ce inganta fatar marasa lafiya na JEB, inganta warkar da raunuka don haka rage haɗarin cututtuka da za su iya haifar da sepsis da mutuwa da wuri."

- Dr Rognoni

Sunan baiwa: Inganta farfadowar fata a cikin JEB ta hanyar niyya ga integrin αvβ6.

Junctional epidermolysis bullosa (JEB) cuta ce ta fata da ba kasafai ba ke haifar da kumburi mai yaduwa da raunin rauni. Wannan yana faruwa ne ta hanyar asarar mahimman sunadaran da ke ɗaure murfin fata zuwa sauran jiki. Mafi tsanani nau'i, JEB mai tsanani, yana faruwa ne ta hanyar asarar aikin laminin-332 wani mahimmin sashi na tsarin ƙulla fata. Marasa lafiya tare da JEB suna fama da gazawar ci gaba, rashin warkar da rauni, matsanancin ciwon fata da haɗarin guba na jini (sepsis). Yaran da aka gano suna da JEB mai tsanani kusan duk suna mutuwa kafin cikarsu ta biyu kuma ya zuwa yanzu babu wasu ingantattun magunguna don dakatarwa ko warkar da wannan cuta mai kisa. Mun gano cewa hanyar siginar haɓakar haɓakar beta (TGFβ) tana da ƙarfi a cikin fata na JEB. Mun yi imanin wannan ya faru ne saboda yawancin matakan integrin αvβ6, babban mai kula da siginar TGFβ a cikin fata, wanda kuma aka lura a cikin raunuka na kullum, fibrosis da halayen rigakafi na fata. Za mu bincika ayyukan αvβ6 a cikin fata na JEB ta amfani da samfuran al'adun mu na in vitro cell (Aim-1 & 2) kuma muyi amfani da samfurin cutar mu na JEB don fahimtar rawar αvβ6 a cikin fata na yau da kullun da warkar da rauni (Aim-3). A ƙarshe, za mu toshe αvβ6 integrin a cikin samfurin mu na JEB kuma muyi nazarin yadda yake hana yawan aiki na TGFβ kuma da fatan inganta gyaran fata na JEB (Aim-4). Binciken mu na farko na asibiti zai ƙayyade idan zaɓin αvβ6 integrin zai iya ba da dama na warkewa a cikin JEB da yuwuwar sauran nau'ikan EB tare da siginar αvβ6 da TGFβ da aka soke.

JEB ba a iya warkewa a halin yanzu kuma jiyya na yanzu suna mayar da hankali kan sarrafa blisters, sarrafa cututtuka da hana rikitarwa. Tushen cutar shine asarar furotin mai suna laminin-332 daga fata. Bayananmu sun gano cewa takamaiman mai karɓa na mannewa tantanin halitta, mai suna αvβ6 integrin, yana haɓaka sosai a cikin fata na JEB, wanda kuma ana lura dashi a cikin raunuka na yau da kullun, fibrosis da ciwace-ciwacen daji. αvβ6 integrin ba wai kawai yana taimakawa ƙwayoyin fata don mannewa da ƙaura ba amma kuma yana sarrafa ayyukan abubuwan haɓaka mai ƙarfi, gami da TGFβ. Yawan aiki na TGFβ yana haifar da lahani na warkar da rauni da kumburin fata. Yin amfani da samfuran mu na musamman na JEB, za mu ƙayyade rawar αvβ6 integrin a cikin fata na JEB. Za mu bincika idan toshe aikin αvβ6 integrin yana da yuwuwar inganta warkar da rauni a cikin JEB. Yin niyya αvβ6 integrin bazai zama magani mai warkewa ba, duk da haka, tsarinmu yana da yuwuwar kula da siginar haɓakar cututtukan cututtuka kamar TGFβ da goyan bayan warkar da fatar fata, inganta ingancin rayuwa da rayuwar marasa lafiya na JEB. Saboda αvβ6 integrin da TGFβ kuma an soke su a cikin nau'ikan nau'ikan EB da yawa, bincikenmu zai tallafawa ci gaban warkewa don wasu cututtukan fata.

Domin 2025.