McKnight Endowment Fund rau Neuroscience tau xaiv plaub txoj haujlwm kom tau txais 2024 Neurobiology of Brain Disorders Awards. Cov khoom plig yuav tag nrho $1.2 lab rau kev tshawb fawb txog biology ntawm cov kab mob hauv hlwb, nrog rau txhua qhov haujlwm tau txais $100,000 ib xyoos hauv txhua peb lub xyoos tom ntej rau tag nrho $300,000 nyiaj pab rau ib qhov project.
Cov Neurobiology ntawm Lub Hlwb Hlwb (NBD) Khoom plig txhawb nqa cov kev tshawb fawb tshiab los ntawm Asmeskas cov kws tshawb fawb uas kawm txog neurological thiab lub hlwb. Cov khoom plig txhawb kom muaj kev sib koom tes ntawm cov hauv nruab nrab thiab cov kws kho mob hlwb txhawm rau txhais cov kev tshawb pom txog lub hlwb thiab lub paj hlwb mus rau kev kuaj mob thiab tshuaj kho kom txhim kho tib neeg kev noj qab haus huv.
Ib qho kev txaus siab ntxiv yog qhov kev koom tes ntawm ib puag ncig rau kev puas hlwb. Thaum ntxov-lub neej kev ntxhov siab ib puag ncig yog ib qho tseem ceeb pov tseg rau yav tom ntej neurological thiab puas siab puas ntsws mob. Cov kev tshawb fawb pom tias cov zej zog ntawm cov xim muaj kev pheej hmoo siab dua rau cov kev ntxhov siab no, uas muaj xws li ib puag ncig (xws li huab cua, khoom noj khoom haus, raug tshuaj lom neeg, muaj kuab paug) mus rau kev sib raug zoo (xws li tsev neeg, kev kawm, vaj tse, kev txom nyem). Los ntawm kev pom kev kho mob, kev nkag siab txog qhov xwm txheej ib puag ncig ua rau muaj kab mob hauv hlwb yog qhov tseem ceeb rau kev txhim kho cov kev kho mob zoo.
"Los ntawm kev nthuav peb txoj kev nkag siab txog yuav ua li cas cov kab mob hauv lub hlwb txhim kho mus rau kev tshawb nrhiav cov kev kho tshiab tshiab rau cov kab mob hlwb, cov kws tshawb fawb tau xaiv rau lub xyoo no tau rhuav tshem qhov tseem ceeb hauv kev tshawb fawb txog kev puas hlwb ntawm cov kab mob neurological," said Ming Guo, MD, Ph.D., lub rooj zaum. ntawm pawg neeg muab khoom plig, Laurie & Steven C. Gordon Thawj Tswj Hwm ntawm Neurosciences, thiab xibfwb hauv Neurology & Pharmacology ntawm UCLA David Geffen Tsev Kawm Ntawv Tshuaj. "Lawv tab tom kawm txog lub hauv paus ntawm kev puas tsuaj loj thiab kev hloov pauv lub neej, suav nrog cov qog nqaij hlav hauv hlwb, Parkinson's Disease thiab Alzheimer's Disease, nce cov tswv yim uas tuaj yeem ua rau muaj kev nkag siab tshiab txog yuav ua li cas lub hlwb ua haujlwm thiab muaj peev xwm txheeb xyuas cov kev kho mob rau cov kab mob hauv lub paj hlwb uas tsis tuaj yeem kho tau yav tom ntej. ”
Cov khoom plig tau txais kev tshoov siab los ntawm kev nyiam ntawm William L. McKnight, uas tau tsim McKnight Foundation hauv 1953 thiab xav txhawb kev tshawb fawb txog kab mob hlwb. Nws tus ntxhais, Virginia McKnight Binger, thiab McKnight Foundation pawg thawj coj tau tsim McKnight neuroscience program hauv nws txoj kev hwm xyoo 1977.
Ntau qhov khoom plig tau muab txhua xyoo. Xyoo no plaub qhov khoom plig yog:
Aparna Bhaduri, Ph.D. thiab co-principal investigator Kunal Patel, MD
(Bhaduri) Assistant xibfwb, Biological Chemistry
(Patel) Neurosurgery, University of California - Los Angeles
Characterizing the Context: Lub luag hauj lwm ntawm Microenvironment hauv Shaping Human Glioblastoma
Aryn Gittis, Ph.D.
xib fwb, Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA
Tshawb xyuas Circuits thiab Mechanisms uas txhawb kev rov qab mus ntev ntawm kev txav hauv Dopamine Depleted nas
Thanh Hoang, Ph.D.
Assistant xibfwb, Department of Ophthalmology, Department of Cell & Developmental Biology, Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
Hauv vivo Reprogramming ntawm Astrocytes rau hauv Neurons rau Kev Kho Mob Parkinson's Disease
Jason Shepherd, Ph.D.
xibfwb, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT
Virus-Like Intercellular Transmission of Tau in Alzheimer's Disease
Nrog 134 tsab ntawv xav tau txais xyoo no, cov khoom plig muaj kev sib tw heev. Pawg neeg ntawm cov kws tshawb fawb txawv teb chaws tshuaj xyuas cov ntawv thiab caw ob peb tus kws tshawb fawb los xa cov lus pom zoo. Ntxiv rau Dr. Guo, pawg thawj coj suav nrog Susanne Ahmari, MD, Ph.D., University of Pittsburgh Tsev Kawm Ntawv Tshuaj; Gloria Choi, Ph.D., Massachusetts Institute of Technology; André Fenton, Ph.D., New York University; Joseph G. Gleeson, MD, University of California San Diego; Tom Lloyd, MD, Ph.D., Baylor College of Medicine; thiab Michael Shadlen, MD, Ph.D., Columbia University.
Daim ntawv thov rau Letters of Intent rau 2025 khoom plig qhib rau Lub Xya Hli 30, 2024.
Hais txog McKnight Endowment Fund rau Neuroscience
McKnight Endowment Fund rau Neuroscience yog ib lub koom haum ywj pheej uas tsuas yog los ntawm McKnight Foundation ntawm Minneapolis, Minnesota, thiab coj los ntawm pawg thawj coj ntawm cov neeg paub txog paj hlwb ntawm ib ncig ntawm lub teb chaws. Lub koom haum McKnight Foundation tau txhawb kev tshawb nrhiav txog kev nyuab siab txij thaum xyoo 1977. Lub Foundation tau tsim Lub Chaw Khiav Hauj Lwm Nyiaj Txiag hauv xyoo 1986 los ua kom tiav ib qho ntawm qhov kev xav ntawm founder William L. McKnight (1887-1978), yog ib tus thawj coj ntawm lub tuam txhab 3M.
Ntxiv nrog rau Neurobiology of Brain Disorders Awards, cov nyiaj txais txiaj ntsig kuj tseem muab cov nyiaj tau txais txiaj ntsig txhua xyoo los ntawm McKnight Scholar Awards, txhawb nqa cov kws tshawb fawb hauv cov theem pib ntawm lawv txoj haujlwm tshawb fawb.
Neurobiology ntawm Lub Hlwb Xiam Hlwb Lub Zog
Aparna Bhaduri, Ph.D., Assistant Professor, Biological Chemistry, thiab co-principal investigator Kunal Patel, MD, Neurosurgery, University of California - Los Angeles
Characterizing cov ntsiab lus: Lub luag hauj lwm ntawm Microenvironment hauv Shaping Human Glioblastoma:
Cov kev mob tshwm sim rau cov neeg tau kuaj pom tias muaj glioblastoma, ib hom mob qog noj ntshav hauv lub hlwb, tau hloov me ntsis hauv kaum xyoo. Ib qho kev sib tw yog tias cov txheej txheem uas glioblastoma tsim thiab kis tau tsis zoo. Cov qauv nas tsuas tuaj yeem qhia cov kws tshawb fawb ntau heev, thiab kev tshawb fawb ntawm cov qog tshem tawm ntawm lub hlwb tsis qhia tias nws loj hlob li cas.
Dr. Bhaduri lub chaw kuaj mob tshawb fawb seb lub hlwb tsim kho li cas thiab qee hom cell reactivated nyob rau hauv cov ntaub ntawv ntawm mob qog noj ntshav hlwb, mimicking theem ntawm lub hlwb kev loj hlob tab sis coopted los ntawm cov qog. Kev koom tes nrog Dr. Patel, tus kws kho mob neurosurgeon tshwj xeeb hauv kev phais glioblastoma, Bhaduri's lab yuav siv cov txheej txheem tshiab los tsim cov tshuab siv organoids tsim los ntawm cov kab cell uas ze ze rau tib neeg lub hlwb ib puag ncig thiab tom qab ntawd cog, loj hlob thiab kawm cov qog nqaij hlav Patel sau los ntawm cov neeg mob phais. . Patel tau tsim txoj hauv kev kom pom cov qog uas tso cai rau nws tshem tawm qee lub hlwb peripheral uas cuam tshuam nrog cov teeb meem ntawm lub hlwb, tshwj xeeb tshaj yog rau kev tshawb fawb.
Bhaduri pab neeg yuav tshawb nrhiav kev sib raug zoo ntawm cov kab mob glioblastoma cell hom - lawv hloov li cas thaum cov qog loj hlob tuaj, thiab ntawm lub luag haujlwm ntawm cov hlwb sib txawv, txawm tias nyob hauv cov tub ntxhais, qhov chaw nruab nrab lossis ib feem ntawm cov qog - thiab tseem saib seb cov qog hlwb cuam tshuam li cas. nrog ib puag ncig cov hlwb. Nkag siab qhov kev sib txuas ntawm txoj kev loj hlob thiab glioblastoma, thiab yuav ua li cas cov qog cuam tshuam nrog nws ib puag ncig, yuav qhia tau txoj hauv kev los cuam tshuam nws.
Aryn Gittis, Ph.D., xibfwb, Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA
Tshawb xyuas Circuits thiab Mechanisms uas txhawb kev rov qab mus ntev ntawm kev txav hauv Dopamine Depleted nas
To taub yuav ua li cas neural circuits tswj kev txav mus los ntawm tib neeg, thiab yuav ua li cas rov qab cov circuits tom qab raug mob lossis puas tsuaj, yog qhov tseem ceeb ntawm Dr. Gittis's lab. Nws txoj kev tshawb fawb tshiab tshawb nrhiav txoj hauv kev los coj mus rau hauv lub hlwb lub cev kom zoo los pab daws cov teebmeem ntawm dopamine depletion - tus yam ntxwv tseem ceeb ntawm Parkinson's Disease- thiab txhim kho kev txav mus los ntev dua ntawm lub sijhawm siv hluav taws xob impulses.
Kev ua kom lub hlwb sib sib zog nqus, uas cov xaim cog rau hauv lub hlwb xa cov nqi hluav taws xob tsis tu ncua, tau txais kev pom zoo thiab siv los pab txo cov tsos mob ntawm Parkinson's Disease rau qee lub sijhawm. Txawm li cas los xij, nws tsuas yog hais txog cov tsos mob, uas rov tshwm sim tam sim ntawd thaum tus nqi raug kaw. Gittis lub chaw kuaj mob txhawm rau nrhiav kom paub meej tias txoj hauv kev neuronal yuav tsum tau ua li cas rau kev rov qab locomotor, yuav ua li cas hluav taws xob pulses tuaj yeem "tso" kom cuam tshuam rau cov neeg nyob hauv cov neeg no, thiab yuav ua li cas cov subpopulations tuaj yeem txhawb nqa los kho lawv tus kheej, muab kev pab ntev dua los ntawm cov tsos mob, txawm tias tsis tas li stimulation.
Kev ua haujlwm ua ntej qhia tau hais tias kev cog lus: Ua haujlwm nrog tus qauv dopamine-depleted nas, Gittis thiab nws pab neeg tau txheeb xyuas cov subpopulations ntawm neurons hauv lub hlwb qia tsim nyog rau kev kho cov tsos mob. Zoo siab heev, thaum txhawb nqa nrog lub mem tes ntawm kev ua tib zoo tu hluav taws xob (tshwj tsis yog qhov ntws tas mus li) lub hlwb kev ua haujlwm tau hloov mus rau hauv txoj hauv kev uas ua rau ntau teev ntawm kev txhim kho kev txav mus los tsis muaj kev txhawb nqa ntxiv. Nws txoj kev tshawb fawb lub hom phiaj los txiav txim siab seb cov kev hloov pauv no puas tuaj yeem ua tau mus tas li kom pib kho thiab rov ua cov kab mob neural.
Thanh Hoang, Ph.D., Assistant xibfwb, Department of Ophthalmology, Department of Cell & Developmental Biology, Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
Hauv vivo Reprogramming ntawm Astrocytes rau hauv Neurons rau Kev Kho Mob Parkinson's Disease
Neurons ntawm lub hauv paus paj hlwb (CNS) yog qhov tseem ceeb rau kev sib koom tes hauv lub cev, tab sis lawv muaj peev xwm ua rau raug mob. Thaum puas lawm, cov teebmeem tuaj yeem hloov tsis tau vim neurons tsis kho lossis hloov lawv tus kheej. Hauv Parkinson's Disease, dopaminergic neurons tau poob lawv txoj haujlwm, depleting dopamine hauv hlwb. Cov kev kho mob tam sim no tsom rau kev txo cov tsos mob xws li kev txhim kho lub cev muaj zog. Dr. Hoang tab tom siv txoj hauv kev sib txawv hauv nws txoj kev tshawb fawb: Nrhiav txoj hauv kev los kho cov hlwb endogenous glial hauv lub hlwb rau hauv cov neurons tshiab, rov ua haujlwm rau lub hlwb.
Hoang's lab tau ua pov thawj lub tswv yim siv cov paj hlwb retinal. Siv tus qauv nas, Hoang txheeb xyuas cov noob hauv cov hlwb retinal glial uas ua raws li cov tshuaj tiv thaiv, tiv thaiv cov hlwb los ntawm kev hloov mus rau cov neurons. Ib txhij poob ntawm kev ua haujlwm rau plaub lub noob tau coj mus rau kev hloov pauv yuav luag tiav ntawm cov hlwb glial mus rau hauv cov hlwb hlwb. Nws txoj kev tshawb fawb lub hom phiaj los txiav txim siab seb tib lub hauv paus ntsiab lus tuaj yeem siv rau astrocytes, ntau hom glial cell hauv CNS, uas zoo ib yam li cov retinal glia los ntawm nws lub chaw kuaj mob yav dhau los.
Hauv nws txoj kev tshawb fawb tshiab, Hoang lub hom phiaj kom ncav cuag kev siv tshuaj kho mob. Nws tab tom ua haujlwm kom ua tiav cov txheej txheem hauv vivo txhawm rau txhawm rau tiv thaiv cov tshuaj tua kab mob hauv astrocytes ntawm adeno-associated virus (AAV) vector. Nws txoj kev tshawb fawb yuav xub txheeb xyuas cov hom neurons uas tshwm sim los ntawm cov txheej txheem - ntau hom tshwm sim - thiab tom qab ntawd nrhiav kev txiav txim siab seb yam twg yuav tsum tau los txhawb txoj kev loj hlob thiab kev loj hlob ntawm dopaminergic neurons tshwj xeeb. Txoj haujlwm no tau cog lus tias yuav txhawb nqa kev tshawb fawb ntawm cell reprogramming, nrog rau kev cuam tshuam rau ntau yam kev puas hlwb ntxiv rau Parkinson's Disease.
Jason Shepherd, Ph.D., xibfwb, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT
Virus-Like Intercellular Transmission of Tau in Alzheimer's Disease
Ntau xyoo ntawm kev tshawb fawb tau nthuav dav peb txoj kev nkag siab ntawm Alzheimer's Disease, cim los ntawm kev paub txog kev poob qis, tab sis ntau qhov tseem yuav tau kawm txog nws cov laj thawj thiab seb cov kab mob kis hauv lub hlwb li cas. Dr. Shepherd thiab nws lub chaw kuaj mob tau tsom mus rau lub luag haujlwm ntawm tau, muaj protein ntau nyob rau hauv cov hlwb hlwb uas tuaj yeem ua rau lub cev tsis zoo thiab muaj hnub nyoog. Muaj kev sib raug zoo ntawm tus nqi ntawm misfolded tau thiab kev paub txog kev poob qis hauv Alzheimer's disease. Txhawm rau tiv thaiv cov cell, misfolded tau yuav tsum tau muab tshem tawm ua ntej nws tsim kom muaj tshuaj lom thiab ua rau cell tuag. Txawm li cas los xij, misfolded tau tso tawm los ntawm cov hlwb tuaj yeem kis tau pathology mus rau lwm lub hlwb thiab thoob plaws lub hlwb.
Qhov tseeb npaum li cas tau raug tso tawm los ntawm cov hlwb tsis paub meej, tab sis qhov no yuav tshwm sim li "liab qab" protein los yog ntim rau hauv daim nyias nyias qhwv extracellular vesicles (EVs). Shepherd pab pawg tab tom tshawb nrhiav qhov muaj peev xwm thib ob no tom qab qhov kev tshawb pom tshiab los ntawm lub chaw sim: tias Arc, cov noob caj noob ces tseem ceeb rau synaptic plasticity thiab kev nco ua ke, tej zaum yuav tau hloov zuj zus los ntawm cov khoom qub qub zoo li retrovirus thiab khaws lub peev xwm tsim EVs los ntawm kev ua tus kab mob- zoo li capsids uas pob khoom thiab xa mus rau cov hlwb nyob ze. Arc khi Tau, yog li Arc EVs kuj tseem tuaj yeem kis tus kab mob tsis zoo, ua rau muaj kev loj hlob ntawm Alzheimer's Disease.
Hauv nws txoj kev tshawb fawb tshiab, Shepherd thiab nws pab neeg tsom kom nkag siab txog cov txheej txheem molecular ntawm tau tso tawm hauv EVs, lub luag haujlwm ntawm Arc hauv tau pathology, thiab yuav ua li cas Arc-dependent mechanisms pab txhawb tau kis tau. Kev nkag siab txog cov txheej txheem no thaum kawg tuaj yeem ua rau cov kev kho mob uas txo qis kev sib kis ntawm cov misfolded tau, hloov txoj hauv kev ntawm Alzheimer's Disease pathology.
