The McKnight Endowment Fund for Neuroscience has selected four projects to receive the 2024 Neurobiology of Brain Disorders Awards. The awards will total $1.2 million for research on the biology of brain diseases, with each project receiving $100,000 per year in each of the next three years for a total of $300,000 funded per project.
Abaalmarinta Neurobiology ee Maskaxda Maskaxda (NBD) waxay taageertaa cilmi baaris cusub oo ay sameeyeen saynisyahano Mareykan ah oo baranaya cudurada neerfaha iyo maskaxda. Abaalmarinnadu waxay dhiirrigelinayaan iskaashiga u dhexeeya aasaasiga iyo daaweynta neerfaha si loo turjumo daahfurnaanta sheybaarka ee ku saabsan maskaxda iyo nidaamka neerfaha baaritaanka iyo daaweynta si loo wanaajiyo caafimaadka aadanaha.
Meel dheeraad ah oo xiisaha leh ayaa ah ka qayb qaadashada deegaanka ee cilladaha maskaxda. Cadaadiska deegaanka ee nolosha hore waa arrin awood badan oo meesha ka saarta xanuunnada neerfaha iyo maskaxda ee dambe. Daraasaduhu waxay muujinayaan bulshooyinka midabka leh inay halis sare ugu jiraan walaacyadan, kuwaas oo u dhexeeya deegaanka (sida cimilada, nafaqada, soo-gaadhista kiimikooyinka, wasakhowga) ilaa bulshada (sida qoyska, waxbarashada, guriyeynta, saboolnimada). Marka laga eego dhinaca bukaan-socodka, fahamka sida arrimaha deegaanku uga qaybqaataan cudurka maskaxda ayaa lagama maarmaan u ah horumarinta daawaynta waxtarka leh.
“From expanding our understanding of how brain diseases develop to exploring novel new therapies for brain disorders, the researchers chosen for this year’s award are breaking important ground in neurological research on neurological diseases,” said Ming Guo, M.D., Ph.D., chair of the awards committee, Laurie & Steven C. Gordon Chair of Neurosciences, and Professor in Neurology & Pharmacology at UCLA David Geffen School of Medicine. “They are studying the underpinnings of devastating and life-altering conditions, including malignant brain tumors, Parkinson’s Disease and Alzheimer’s Disease, advancing ideas that could lead to new insights into how the brain works and potentially identify cures for currently incurable neurological disorders in the future.”
The awards are inspired by the interests of William L. McKnight, who founded the McKnight Foundation in 1953 and wanted to support research on brain disease. His daughter, Virginia McKnight Binger, and The McKnight Foundation board established the McKnight neuroscience program in his honor in 1977.
Multiple awards are given each year. This year’s four awards are:
Aparna Bhaduri, Ph.D. and co-principal investigator Kunal Patel, M.D.
(Bhaduri) Assistant Professor, Biological Chemistry
(Patel) Neurosurgery, University of California – Los Angeles
Characterizing the Context: The Role of the Microenvironment in Shaping Human Glioblastoma
Aryn Gittis, Ph.D.
Professor, Waaxda Sayniska Nafleyda, Jaamacadda Carnegie Mellon, Pittsburgh, PA
Baadhitaanka Wareegyada iyo Farsamooyinka Taageera Soo kabashada Dhaqdhaqaaqa Muddada Dheer ee Dopamine-ka Jiirarka Dhammaaday
Thanh Hoang, Ph.D.
Kaaliyaha Professor, Waaxda Indhaha, Waaxda Unugyada & Bayoolaji Koriinka, Michigan Neuroscience Institute, Jaamacadda Michigan, Ann Arbor, MI
In vivo Dib u habaynta Astrocytes ee Neurons si loogu daweeyo Cudurka Parkinson
Jason Shepherd, Ph.D.
Professor, Spencer Fox Eccles School of Medicine, Jaamacadda Utah, Salt Lake City, UT
Fayraska-sida Gudbinta Intercellular ee Tau ee Cudurka Alzheimers
With 134 letters of intent received this year, the awards are highly competitive. A committee of distinguished scientists reviews the letters and invites a select few researchers to submit full proposals. In addition to Dr. Guo, the committee includes Susanne Ahmari, M.D., Ph.D., University of Pittsburgh School of Medicine; Gloria Choi, Ph.D., Massachusetts Institute of Technology; André Fenton, Ph.D., New York University; Joseph G. Gleeson, M.D., University of California San Diego; Tom Lloyd, M.D., Ph.D., Baylor College of Medicine; and Michael Shadlen, M.D., Ph.D., Columbia University.
The application for Letters of Intent for the 2025 awards opens July 30, 2024.
Ku saabsan Sanduuqa Maaliyadda ee McKnight Fund for Neuroscience
Sanduuqa McKnight Fund ee Neuroscience waa urur madax-bannaan oo ay maalgeliso oo kaliya Mashruuca McKnight ee Minneapolis, Minnesota, oo uu hogaaminayey guddi khubaro ah oo ku takhasusay dareemayaasha ka yimaada waddanka. Machadka McKnight Foundation wuxuu taageersanaa cilmi-baarista neurosiyaanka tan iyo 1977-kii. Foundation wuxuu aasaasay Sanduuqa Dhexe ee Bixinta 1986 si uu u fuliyo mid ka mid ah ujeedooyinka aasaasiga ah ee aasaasaha aasaasaha ah William L. McKnight (1887-1978), mid ka mid ah hoggaamiyayaashii hore ee shirkadda 3M.
In addition to the Neurobiology of Brain Disorders Awards, the endowment fund also provides annual award funding through the McKnight Scholar Awards, supporting neuroscientists in the early stages of their research careers.
Abaalmarinta Neurobiology ee Abaalmarinta Maskaxda
Aparna Bhaduri, Ph.D., Kaaliyaha borofisar, Kiimikada noolaha, iyo baaraha la-shaqeeyaha Kunal Patel, MD, Neurosurgery, University of California – Los Angeles
Astaamaha Macnaha guud: Doorka deegaanka yar yar ee qaabaynta Glioblastoma aadanaha:
Saadaasha dadka laga helay glioblastoma, oo ah nooc ka mid ah kansarka maskaxda ee aasaasiga ah, ayaa wax yar isbeddelay muddo tobanaan sano ah. Hal caqabad ayaa ahayd in habka glioblastoma uu ku horumaro kuna faafo si liidata loo fahmay. Moodooyinka jiirka ayaa kaliya u sheegi kara cilmi-baarayaasha wax badan, iyo daraasadaha burooyinka laga saaray maskaxda ma muujiyaan sida ay u koreen.
Shaybaarka Dr. Bhaduri waxa uu daraaseeyaa sida ay maskaxdu u horumarto iyo sida noocyada unugyada qaarkood dib loogu hawlgeliyo marka laga hadlayo kansarka maskaxda, iyaga oo la jaanqaadaya marxaladaha korriinka maskaxda balse ay isku duba ridaan buro. La shaqaynta Dr. Patel, dhakhtarka neerfaha ee ku takhasusay qalliinnada glioblastoma, shaybaarka Bhaduri wuxuu isticmaali doonaa habab cusub si uu u abuuro nidaamyo la isticmaalayo organoids oo laga soo saaray khadadka unugyada stem kuwaas oo si dhow ula jaan qaadaya deegaanka maskaxda bini'aadamka ka dibna la geliyo, koraan oo baranaya muunadaha buro ee Patel waxay ka soo ururiyaan bukaannada qalliinka. . Patel waxa uu sameeyay habab uu ku sawiro burooyinka taas oo u ogolaanaysa in uu ka saaro qaar ka mid ah unugyada durugsan ee isku xidha arrimaha maskaxda ee ku xeeran, oo xiiso gaar ah u leh cilmi-baadhista.
Kooxda Bhaduri waxay sahamin doontaa xiriirka nasabka ee noocyada unugyada glioblastoma - sida ay isu beddelaan marka ay buradu koraan, iyo doorarka unugyo kala duwan, hadday ku jiraan xudunta, durugsan ama qayb kasta oo ka mid ah burada - iyo sidoo kale waxay eegi doonaan sida unugyada buradu u falgalaan. oo leh unugyo caadi ah oo ku xeeran. Fahamka xidhiidhka ka dhexeeya horumarka iyo glioblastoma, iyo sida burodu ula falgasho deegaankeeda, waxa laga yaabaa inay muujiso siyaabo lagu carqaladeeyo.
Aryn Gittis, Ph.D., Professor, Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA
Baadhitaanka Wareegyada iyo Farsamooyinka Taageera Soo kabashada Dhaqdhaqaaqa Muddada Dheer ee Dopamine-ka Jiirarka Dhammaaday
Fahamka sida wareegyada neerfaha u xakameeyaan dhaqdhaqaaqa bini'aadamka, iyo sida dib loogu tababaro wareegyadaas ka dib dhaawaca ama dhaawaca, waa udub dhexaadka diiradda shaybaarka Dr. Gittis. Cilmi baaristeeda cusub waxay sahamisaa siyaabaha loo geliyo caagagga maskaxda si ay gacan uga geysato hagaajinta saameynta dhimista dopamine - sifada muhiimka ah ee Cudurka Parkinson - iyo hagaajinta dhaqdhaqaaqa dhaqdhaqaaqa muddo dheer iyadoo la isticmaalayo dareen koronto.
Kicinta maskaxda qoto dheer, kaas oo fiilooyinka maskaxda lagu dhex beeray ay bixiyaan kharash koronto oo joogto ah, oo aan khaas ahayn, ayaa la ansixiyay oo loo adeegsaday in lagu nafiso calaamadaha cudurka Parkinson in muddo ah. Si kastaba ha ahaatee, waxay ka hadlaysaa oo kaliya calaamadaha, kuwaas oo isla markiiba soo baxa marka kharashka la damiyo. Shaybaarka Gittis wuxuu higsanayaa in uu helo dhab ahaan waxa waddooyinka neerfaha looga baahan yahay soo kabashada lugaha, sida garaaca korantada loo "habayn karo" si ay u saameeyaan dadkan hoose, iyo sida kuwan hoose ee loo kicin karo si ay dhab ahaantii isu hagaajiyaan, iyaga oo bixinaya nafis waara oo ka yimaada calaamadaha, xitaa iyada oo aan kicin joogto ah.
Shaqada horudhaca ah waxay muujinaysaa ballanqaad: La shaqaynta qaabka jiirka ee dopamine-ka yaraaday, Gittis iyo kooxdeedu waxay aqoonsadeen tiro-hoosaadyo gaar ah oo neerfayaasha maskaxda ah ee lagama maarmaanka u ah nafiska calaamadaha. Si xiiso leh, marka lagu kiciyo garaaca garaaca korantada si taxadar leh loo hagaajiyay (halkii socodka joogtada ah) unugyada dhaqdhaqaaqa ayaa loo beddelaa si ay u keento saacado dhaqdhaqaaq la hagaajiyay iyada oo aan lahayn kicin dheeraad ah. Cilmi-baadhisteedu waxay rabta inay go'aamiso in isbeddelladan dhaqdhaqaaqa la samayn karo si joogto ah si loo bilaabo bogsashada iyo dib-u-habaynta wareegyada neerfaha.
Thanh Hoang, Ph.D., Kaaliyaha Professor, Waaxda Indhaha, Waaxda Unugyada & Bayoolaji Koriinka, Michigan Neuroscience Institute, Jaamacadda Michigan, Ann Arbor, MI
In vivo Dib u habaynta Astrocytes ee Neurons si loogu daweeyo Cudurka Parkinson
Neurons ee habka dhexe ee neerfayaasha (CNS) ayaa muhiim u ah isku-dubbaridka hawlaha jidhka, haddana aad bay ugu nugul yihiin dhaawacyo. Marka ay waxyeello gaarto, saameyntu waxay noqon kartaa mid aan la soo celin karin maadaama neurons aysan si dabiici ah u dayactirin ama aysan is beddelin. Cudurka Parkinson, neerfayaasha dopaminergic waxay lumiyeen shaqadoodii, waxayna baabi'iyeen dopamine ee maskaxda. Daawaynta hadda waxay diiradda saaraan yaraynta calaamadaha sida hagaajinta xakamaynta dhaqdhaqaaqa. Dr. Hoang waxa uu qaadayaa hab ka duwan cilmi-baadhistiisa: Helitaanka habab dib loogu habeeyo unugyada glial-ka ee maskaxda oo loo beddelo neurons cusub, dib u soo celinta shaqada maskaxda.
Shaybaarka Hoang's ayaa xaqiijiyay fikradda iyadoo la adeegsanayo neerfayaasha isha. Isticmaalka qaabka jiirka, Hoang waxa uu aqoonsaday hiddo-wadaha ku jira unugyada glial-ka ee retinal kuwaas oo u shaqeeya sidii wax-joojiyayaal, iyaga oo ka hortagaya in unugyada ay isu beddelaan neurons. Luminta shaqada isku mar ah ee afartaas hiddo-wade ayaa horseeday beddelaad dhammaystiran oo unugyada glial-ka ah ee neerfaha retinal. Cilmi-baaristiisu waxay ujeeddadeedu tahay in la go'aamiyo haddii isla mabda'a lagu dabaqi karo astrocytes, nooca ugu badan ee unugga glial ee CNS, kaas oo si dhow ula mid ah glia-ka isha ee cilmi-baaristii hore ee shaybaarkiisa.
Cilmi-baaristiisa cusub, Hoang wuxuu hiigsanayaa inuu gaaro dhinaca codsiga daweynta. Waxa uu ka shaqaynayaa in uu dhamaystiro habka in vivo si uu u xakameeyo xakamaynta ku jira astrocytes iyada oo loo marayo fayraska adeno-xiriirka leh (AAV). Cilmi baaristiisu waxay marka hore aqoonsan doontaa noocyada neerfayaasha ee ka soo baxa habka - noocyo badan ayaa u muuqda inay ka soo baxaan - ka dibna raadi si loo go'aamiyo waxyaabaha loo baahan yahay si kor loogu qaado horumarinta iyo korriinka dopaminergic neurons gaar ahaan. Shaqadani waxa ay ballan qaadaysaa in ay horumariso cilmiga dib-u-habaynta unugga, iyada oo saamayn ku leh xanuunno badan oo neerfaha ah marka lagu daro Cudurka Parkinson.
Jason Shepherd, Ph.D., Professor, Spencer Fox Eccles School of Medicine, Jaamacadda Utah, Salt Lake City, UT
Fayraska-sida Gudbinta Intercellular ee Tau ee Cudurka Alzheimers
Sannado badan oo cilmi-baaris ah ayaa si weyn u ballaariyay fahamka cudurka Alzheimers, oo lagu calaamadeeyay hoos u dhaca garashada, laakiin wax badan ayaa ka dhiman in laga barto sababaha iyo sida pathology-ku ugu faafo maskaxda. Dr. Shepherd iyo shaybaadhkiisu waxa ay diiradda saarayaan doorka tau, borotiinka ku jira unugyada maskaxda kaas oo noqon kara mid qaldama oo da'da qallafsan. Waxa jira xidhiidh adag oo u dhexeeya qadarka tau ee la qalday iyo hoos u dhaca garashada ee cudurka Alzheimers. Si loo ilaaliyo unugyada, tau qalloocan waxay u baahan tahay in la eryo ka hor intaysan dhismin ilaa heerar sun ah oo aanay sababin dhimashada unugyada. Si kastaba ha ahaatee, tau-ga khaldan ee laga sii daayo unugyada waxay ku faafi kartaa tau pathology unugyo kale iyo maskaxda oo dhan.
Sida saxda ah sida tau looga sii daayo unugyadu ma cadda, laakiin tani waxay u dhici kartaa sidii borotiin "qaawan" ama lagu baakadeeyey xuubabka ka baxsan unugyada unugyada (EVs). Kooxda Shepherd ayaa sahaminaysa suurtagalnimadan labaad ka dib markii la helay shaybaar cusub: Arc, hidde-side neuronal oo muhiim u ah balaastikada synaptika iyo xoojinta xusuusta, ayaa laga yaabaa inay ka soo baxday curiye qadiim ah oo retrovirus u eg oo sii xajistay awoodda samaynta EVs iyadoo la samaynayo fayraska- sida capsids in alaabta baakad oo u dir unugyada u dhow. Arc waxay xidhaa Tau, sidaa darteed Arc EVs waxa kale oo laga yaabaa inay faafiyaan Tau ee la qalday, taas oo gacan ka geysata horumarka Cudurka Alzheimers.
Cilmi-baadhistiisa cusub, Shepherd iyo kooxdiisu waxay higsanayaan inay fahmaan hababka molecular ee sii-deynta tau ee EVs, doorka Arc ee tau pathology, iyo sida hababka ku-tiirsanaanta Arc ay gacan uga geystaan faafitaanka tau. Fahamka hababkaan ayaa ugu dambeyntii horseedi kara daaweyno yareynaya faafitaanka tau ee qalloocan, beddela habka pathology ee Cudurka Alzheimers.
