McKnight Endowment Fund rau Neuroscience tau xaiv plaub txoj haujlwm kom tau txais 2023 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.
Lub Neurobiology of Brain Disorders (NBD) Awards txhawb kev tshawb fawb tshiab los ntawm Asmeskas cov kws tshawb fawb uas tab tom kawm txog cov txheej txheem lom neeg ntawm kev puas hlwb thiab kev puas siab puas ntsws. Cov khoom plig txhawb kom muaj kev sib koom tes thiab kev qhuab qhia sib koom ua ke uas tuaj yeem ua rau muaj kev kuaj pom txog lub hlwb thiab lub paj hlwb thiab yog li kev kuaj mob thiab kev kho mob los 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.
Ming Guo, MD, Ph.D., tus thawj coj ntawm pawg thawj coj khoom plig thiab xibfwb hauv Neurology & Pharmacology tau hais tias "Lub xyoo no pab pawg ntawm McKnight Neurobiology of Brain Disorders tau txais txiaj ntsig yog qhov tseem ceeb ntawm kev tshawb fawb hauv hlwb thiab tau ua qee qhov kev tshawb pom zoo," said Ming Guo, MD, Ph.D. UCLA David Geffen Tsev Kawm Ntawv Tshuaj Kho Mob. "Kev ua haujlwm uas lawv tab tom ua muaj peev xwm ua rau muaj kev kho mob ALS, qaug dab peg, rog rog, thiab mob qog noj ntshav hauv hlwb - mob hnyav uas cuam tshuam rau ntau lab tus tib neeg thoob ntiaj teb."
Cov khoom plig tau txais kev tshoov siab los ntawm kev nyiam ntawm William L. McKnight, uas tau tsim lub McKnight Foundation hauv xyoo 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. Plaub qhov khoom plig xyoo no yog:
Assistant xibfwb ntawm Neuroscience, Yale University Tsev Kawm Ntawv ntawm Tshuaj, New Haven, CT
Mechanism thiab kev ua haujlwm ntawm rov nthuav dav tus kheej-exonization hauv C9orf72 ALS/FTD
Assistant xibfwb ntawm Neurology, Stanford University School of Medicine, Palo Alto, CA
Neuron-rau-OPC synapses nyob rau hauv adaptive thiab maladaptive myelination
Associate Professor, Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA
Adipocyte-brain mitochondrial signaling thiab nws cuam tshuam rau lub hlwb ua haujlwm
Assistant Professor of Neurology, Brigham thiab Women's Hospital & Harvard Medical School, Boston, MA
Lub neurobiology ntawm glioma: Nkag siab txog malignant neural circuits qhia cov qog loj hlob
Nrog 164 tsab ntawv xav tau txais xyoo no, cov khoom plig muaj kev sib tw heev. Pawg neeg ntawm cov kws tshawb fawb tshwj xeeb 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 Sue Ackerman, Ph.D., University of California, San Diego; Susanne Ahmari, MD, Ph.D., University of Pittsburgh Tsev Kawm Ntawv Tshuaj; Andre' Fenton, Ph.D., New York University; Tom Lloyd, MD, Ph.D., Johns Hopkins Medical School; thiab Harry Orr, Ph.D., University of MN.
Hnub kawg rau Tsab Ntawv Lub Hom Phiaj rau lub 2024 khoom plig yog lub Kaum Ib Hlis 1, 2023.
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 lub rooj tsavxwm ntawm cov neeg paub txog kev nyuab siab nyob thoob plaws lub tebchaws. 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, Endowment Fund kuj tseem muab cov khoom plig 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
Junjie Guo, Ph.D., Assistant Professor of Neuroscience, Yale University School of Medicine, New Haven, CT
Mechanism thiab kev ua haujlwm ntawm rov nthuav dav tus kheej-exonization hauv C9orf72 ALS/FTD
Raws li intricate raws li DNA replication txheej txheem, tej zaum yuam kev tshwm sim. Qee cov kab mob neurological txuas nrog rau ib hom kev ua yuam kev hu ua nucleotide rov nthuav dav (NRE), uas ib ntu DNA luv tau rov ua dua thiab ntau dua hauv ntau pua lossis ntau daim ntawv luam. Qhov twg cov kev rov ua dua no tshwm sim hauv cov teeb meem genome: thaum lub sij hawm tseem ceeb hauv kev qhia cov noob hu ua RNA splicing, tsuas yog qee qhov (exons) ntawm RNA uas tau sau los ntawm DNA tau koom ua ke los ua tus xa xov kawg RNA, qhov seem RNA sequences (introns) nruab nrab ntawm exons yuav tawg.
Txawm li cas los xij, qee zaum, intros nrog NREs tsis tawg, tab sis tswj kom qhia txog kev ua ntau yam ntawm cov proteins uas ua rau muaj teeb meem rau cov paj hlwb. Ib qho piv txwv uas paub zoo yog ib qho intron NRE nyob rau hauv ib lub noob hu ua C9orf72, uas yog cov caj ces feem ntau ntawm amyotrophic lateral sclerosis (ALS, los yog Lou Gehrig tus kab mob) thiab frontotemporal dementia (FTD). Hauv nws txoj kev tshawb fawb, Dr. Guo vam tias yuav nthuav tawm tias qhov intron NRE no cuam tshuam RNA splicing li cas thiab ua rau cov tshuaj lom neeg rov ua dua cov proteins.
Guo thiab nws pab neeg yuav xub sim ntau yam ntawm NRE kev hloov pauv kom pom qhov twg tuaj yeem hloov pauv tus qauv sib txuas kom lub intron tuaj yeem dim ntawm kev puas tsuaj. Lawv lub hom phiaj thib ob yuav sim qhov kev xav tias cov kev hloov pauv hauv cov qauv sib txuas yog qhov tseem ceeb rau C9orf72 NRE RNA kom nce nws cov khoom xa tawm ntawm lub xov tooj ntawm tes mus rau hauv cytoplasm thiab qhia ua kom muaj cov protein ntau ntxiv. Thaum kawg, lawv cov kev tshawb fawb yuav tshawb nrhiav qhov muaj peev xwm sib txawv ntawm txoj hauv kev uas txhua lub xov tooj sib txuas nws cov RNAs tuaj yeem piav qhia vim li cas qee hom paj hlwb xws li lub cev muaj zog neurons muaj kev cuam tshuam ntau dua hauv ALS.
Juliet K. Knowles, MD, PhD, Assistant xibfwb ntawm Neurology, Stanford University School of Medicine, Palo Alto, CA
Neuron-rau-OPC synapses nyob rau hauv adaptive thiab maladaptive myelination
Hauv nws lub luag haujlwm ua tus kws kho mob menyuam yaus tshwj xeeb hauv kev qaug dab peg, Dr. Knowles pom ua ntej yuav ua li cas qhov teeb meem ntawm lub paj hlwb (qhov tseeb yog ib qho kev sau los ntawm ntau yam kab mob sib txawv) tau ntsib thiab nws ua li cas. Raws li ib tug kws kho mob neuroscientist, nws muaj lub cib fim los pab qhia seb yuav ua li cas thiab vim li cas. Knowles thiab nws pab neeg tab tom tsom mus rau lawv cov kev tshawb fawb txog lub luag haujlwm ntawm kev ua haujlwm neuronal hauv myelination hauv cov neeg mob uas muaj mob vwm, ib hom kab mob uas tshwm sim los ntawm kev muaj qaug dab peg thiab tsis muaj qaug dab peg.
Myelination yog cov txheej txheem uas cov axons (projections) ntawm cov neurons tau encased hauv myelin, uas txhim kho qhov ceev ntawm axon teeb liab kis tau tus mob, thiab ua rau neural tes hauj lwm zoo dua. Cov txheej txheem cuam tshuam nrog oligodendrocyte progenitor cells (OPCs) uas tuaj yeem tsim mus rau hauv oligodendrocytes, cov hlwb uas tsim cov myelin. Hauv kev tshawb fawb yav dhau los, Knowles tau tshaj tawm tias cov haujlwm neural ntawm kev qaug dab peg txhawb nqa myelination ntawm qhov qaug dab peg, ua kom muaj txiaj ntsig zoo dua. Qhov no tshwm sim ua rau muaj qhov nce ntawm qhov tsis tuaj yeem qaug dab peg thiab mob hnyav; thaum Knowles thiab nws pab neeg tau thaiv OPCs cov lus teb rau kev ua haujlwm ntawm neural, qaug dab peg-induced myelination tsis tshwm sim, thiab qaug dab peg tsis ua tiav.
Knowles 'kev tshawb fawb tshiab tam sim no yuav tshawb nrhiav qhov no tshwm sim li cas thiab txheeb xyuas cov kev ua tau zoo rau kev kho mob yav tom ntej. Ib lub hom phiaj yuav sau cov neuron rau OPC synapses nyob rau hauv ob qho tib si epileptic thiab noj qab nyob zoo nas qauv. Lub hom phiaj thib ob yuav muab piv rau neuron-rau-OPC synaptic kev ua si thiab synaptic gene qhia hauv cov nas noj qab haus huv lossis mob vwm - tshwj xeeb tsom rau qhov kev txhawb nqa myelination los ntawm kev qaug dab peg txawv ntawm qhov kev txhawb nqa los ntawm kev kawm. Qhov thib peb lub hom phiaj yuav tshawb nrhiav qhov cuam tshuam li cas tom qab synaptic receptors ntawm oligodendrocytes cuam tshuam rau kev mob vwm, tsis yog ntawm qaug dab peg, tab sis cov tsos mob cuam tshuam xws li cuam tshuam kev pw tsaug zog thiab kev paub tsis meej, ob qho tib si muaj ntau rau cov tib neeg cuam tshuam los ntawm kev qaug dab peg.
Akhila Rajan, Ph.D., Associate Professor, Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA
Adipocyte-brain mitochondrial signaling thiab nws cuam tshuam rau lub hlwb ua haujlwm
Kev sib txuas lus ntawm lub cev thiab lub hlwb yog qhov tseem ceeb rau tus tsiaj txoj sia nyob thiab kev noj qab haus huv. Cov teeb liab qhia rau lub hlwb thaum lub cev xav tau lub zog ntau dua, tshaib plab, lossis xav tau pw, txav los yog ua lwm yam haujlwm suav tsis txheeb. Tab sis kev tshawb fawb tsis ntev los no tau qhia tias kev sib txuas lus tuaj yeem suav nrog ntau dua li cov tshuaj hormones - cov ntaub ntawv tseem tuaj yeem xa mus rau hlwb hlwb. Dr. Rajan txoj kev tshawb fawb tsom mus rau qhov tshwm sim ntawm cov roj hlwb (adipocytes) xa cov khoom ntawm mitochondria - cov organelles hauv cov hlwb uas tsim lub zog, ntawm lwm yam - rau lub hlwb, thiab yuav ua li cas cuam tshuam rau lub hlwb.
Cov kev tshawb fawb yav dhau los tau pom tias thaum cov khoom mitochondrial no ncav cuag lub hlwb, nws ua rau tus qauv ya Rajan pab neeg ua haujlwm nrog tshaib plab, tshwj xeeb tshaj yog rau cov khoom noj qab zib siab, txhawb lub voj voog ntawm kev rog thiab xa khoom ntxiv. Muaj kev paub txog kev sib raug zoo ntawm kev rog thiab ntau yam kab mob hauv lub paj hlwb, suav nrog kev pw tsaug zog tsis zoo thiab kev paub tsis meej, thiab qhov kev tshawb fawb tshiab no vam tias yuav ua rau pom kev ntawm cov kev sib txuas no thiab muaj peev xwm txheeb xyuas lub hom phiaj rau kev kho mob yav tom ntej.
Ua hauj lwm nrog tus qauv ya, Rajan thiab nws pab neeg tsom xyuas seb cov khoom no ntawm mitochondria puas tau nkag mus rau cov neurons hauv lub hlwb yam tsis tau degraded; Yuav ua li cas tshwm sim thaum cov khoom ntawm cov roj cell mitochondria integrate nrog neuronal mitochondria, tshwj xeeb li cas nws hloov tus tsiaj tus cwj pwm ntawm kev pw tsaug zog thiab pub mis; thiab dab tsi cuam tshuam cov txheej txheem no rau kev noj qab haus huv neuronal tag nrho. Cov kev tshawb fawb yuav ua kom zoo dua ntawm cov kev hloov pauv caj ces meej heev uas Rajan lub chaw sim ua tau zoo, koom nrog kev sib tham txog kev qhuab qhia los ntawm cov neeg ua haujlwm hauv chav kuaj, thiab siv cov kab kab mob siab tshaj plaws uas cia cov pab pawg sau ntawv pub noj thiab hloov tus cwj pwm ntawm qib tsis muaj rau cov tiam dhau los. ntawm cov kws tshawb fawb.
Humsa Venkatesh, Ph.D., Assistant Professor of Neurology, Brigham thiab Women's Hospital & Harvard Medical School, Boston, MA
Lub neurobiology ntawm glioma: Nkag siab txog malignant neural circuits qhia cov qog loj hlob
Cov qog nqaij hlav, nrog rau cov qog hlwb, ib txwm tau kawm ntawm qib cellular lossis molecular. Cov kws tshawb fawb tab tom teb cov lus nug xws li cov subpopulation ntawm cov hlwb koom nrog, lawv hloov pauv li cas, thiab peb tuaj yeem ua li cas rau cov hlwb tsis zoo kom lawv tsis txhob rov ua dua? Dr. Venkatesh txaus siab saib yuav ua li cas lub paj hlwb tseem koom nrog kev mob qog noj ntshav thiab twb tau pom tias cov neurons tsim synaptic txuas rau cov qog nqaij hlav cancer.
Venkatesh thiab nws lub chaw kuaj mob tab tom kawm ob qho tib si thawj thiab theem nrab cov qog hlwb tab sis muaj pov thawj tias cov kev tshawb pom no siv rau cov qog nqaij hlav hauv lwm qhov ntawm lub cev. Kev pom tias cov qog muaj kev cuam tshuam nrog cov neurons, thiab tsis yog tua cov paj hlwb raws li tau xav, tau qhib ntau qhov ua tau. Cov kev loj hlob malignant no tau txais cov cim qhia los ntawm lub paj hlwb npaj kom dhau cov ntaub ntawv mus rau lwm lub hlwb thiab hloov pauv lawv rov qab qhia cov qog nqaij hlav kom loj hlob. Tam sim no cov kws tshawb fawb tuaj yeem tshawb nrhiav yuav ua li cas siv lub paj hlwb los pab kho lossis tswj tus kab mob malignant no. Hauv kev txhim kho zoo siab, Venkatesh txoj haujlwm yav dhau los hauv qhov chaw no twb tau coj mus rau kev sim tshuaj uas rov tsim cov tshuaj uas twb muaj lawm tsom rau lub paj hlwb thiab siv rau kev kho mob qog noj ntshav.
Qhov kev tshawb fawb tshiab no mus ntxiv rau kev nkag siab txog cov txheej txheem tswj hwm kev ua haujlwm ntawm neural circuit-tsav glioma kev loj hlob. Siv cov thev naus laus zis thev naus laus zis thiab cov kab mob tau los ntawm cov neeg mob, Venkatesh yuav tuaj yeem hloov kho thiab kawm cov kab mob qog nqaij hlav tsis zoo, suav nrog ob leeg neurons thiab qog hlwb, uas cuam tshuam rau kev loj hlob ntawm qog noj ntshav. Kev nkag siab txog qhov kev ua haujlwm ntawm lub luag haujlwm no thiab yuav ua li cas nws tuaj yeem raug tsom yam tsis muaj kev cuam tshuam kev noj qab haus huv neuronal tuaj yeem qhib cov haujlwm tshiab ntawm kev tshawb fawb qog noj ntshav thiab cov sijhawm kho tshiab.
