Hla mus rau cov ntsiab lus
10 min nyeem

McKnight Awards $1.2 lab rau Kev Tshawb Fawb Txog Kev Nyuaj Siab

Kaum Ob Hlis 13, 2021

McKnight Endowment Fund rau Neuroscience tau xaiv plaub txoj haujlwm kom tau txais 2022 Neurobiology of Brain Disorders Awards. Cov khoom plig yuav tag nrho $1.2 lab nyob rau peb lub xyoos rau kev tshawb fawb txog biology ntawm cov kab mob hlwb, nrog rau txhua qhov haujlwm tau txais $300,000 ntawm 2022 thiab 2025.

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.

Ming Guo, MD, Ph.D., tus thawj coj ntawm pawg thawj coj saib xyuas kev noj qab haus huv ntawm Neurobiology of the Brain Disorders, said Ming Guo, MD, Ph.D. & Pharmacology ntawm UCLA David Geffen Lub Tsev Kawm Ntawv Tshuaj Kho Mob thiab Tus Thawj Coj ntawm Kev Laus Chaw ntawm UCLA. "Cov neeg tau txais txiaj ntsig xyoo no tab tom tshawb fawb txog cov kab mob thiab cov xwm txheej uas cuam tshuam rau ntau lab tus neeg mob. Lawv txoj haujlwm tsom mus rau cov teeb meem ua pa thiab lub hlwb circuit, kev siv tshuaj yeeb, kev sib cuam tshuam hauv plab-hlwb hauv qab anorexia, thiab hedonic noj tus cwj pwm thiab rog. Los ntawm kev nkag siab txog cov kab mob neurobiology, peb qhib qhov rooj rau txoj hauv kev tshiab los tiv thaiv thiab kho cov kab mob hlwb no. "

Cov khoom plig tau txais kev tshoov siab los ntawm kev nyiam ntawm William L. McKnight, uas tau tsim 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:

  • Lisa Beutler, MD, Ph.D., Assistant Professor of Medicine in Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, IL
    Dissecting the gut-brain dynamics underlying anorexia: Dr. Beutler nrhiav cov ntaub ntawv ntawm lub plab-hlwb neural circuits cuam tshuam rau hauv inflammatory-mediated anorexia, txheeb xyuas qhov ua rau muaj kev cuam tshuam ntawm cov circuits, thiab nrhiav pom neural substrates uas tuaj yeem pab kov yeej tus mob.
  • Jeremy Day, Ph.D., Associate Professor, Department of Neurobiology, Heersink Tsev Kawm Ntawv ntawm Tshuaj, University of Alabama - Birmingham; thiab Ian Maze, Ph.D., Xib fwb – Departments of Neuroscience and Pharmacological Sciences, Director – Center for Neural Epigenome Engineering, Icahn School of Medicine ntawm Mount Sinai, New York City
    Leveraging single-cell epigenomics rau lub hom phiaj manipulation ntawm tshuaj-activated ensembles: Drs. Hnub thiab Maze tab tom tshawb nrhiav cov epigenetic underpinnings ntawm kev quav tshuaj, txheeb xyuas cov neural ensembles uas tau hijacked los ntawm kev siv yeeb tshuaj, yog li pov tseg cov tib neeg rov qab.
  • Stephan Lammel, Ph.D., Associate Professor of Neurobiology, University of California - Berkeley
    Neurotensin mediated kev cai ntawm hedonic noj tus cwj pwm thiab rog: Dr. Lammel txoj haujlwm tsom mus rau cov txheej txheem neural thiab cheeb tsam hauv lub hlwb koom nrog kev noj zaub mov ntau dhau ntawm cov zaub mov muaj calorie ntau thiab nws cov kev cai.
  • Lindsay Schwarz, Ph.D., Assistant Professor in Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN
    Txheeb xyuas lub hlwb circuits uas txuas ua pa thiab kev paub txog lub xeev: Dr. Schwarz lub hom phiaj txhawm rau txheeb xyuas qhov ua tsis taus pa ntawm cov neurons tau xaiv los ntawm lub cev thiab kev txawj ntse thiab qhia cov cheeb tsam hauv hlwb uas lawv txuas nrog.

Nrog 106 tsab ntawv xav tau txais xyoo no, cov khoom plig muaj kev sib tw heev. Pawg neeg ntawm cov kws tshawb fawb muaj txiaj ntsig 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; Robert Edwards, MD, University of California, San Francisco; Andre' Fenton, Ph.D., New York University; Tom Lloyd, MD, Ph.D., Johns Hopkins Medical School; thiab Harry Orr, Ph.D., University of MN.

2023 khoom plig hloov tshiab: Lub sijhawm xa thiab xaiv rau Neurobiology of Brain Disorders Awards tau hloov pauv. Lub sijhawm kawg rau Cov Ntawv Qhia Txog Lub Hom Phiaj rau 2023 khoom plig yuav tshaj tawm nyob rau nruab nrab-2022.

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.

Cov Nyiaj The Endowment Fund ua peb hom khoom plig txhua xyoo. Ntxiv nrog rau Neurobiology ntawm Lub Hlwb Tsis Muaj Zog Cov Khoom Noj, lawv yog McKnight Technological Innovations hauv Neuroscience Awards, muab cov nyiaj noob los tsim cov kev tsim txuj ci los txhawb kev tshawb fawb lub hlwb; thiab McKnight Scholar Awards, txhawb nqa cov kws paub txog khoom plig ntawm cov theem pib ntawm lawv cov haujlwm kev tshawb nrhiav.

Bios

Lisa Beutler, MD, Ph.D., Assistant Professor of Medicine in Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, IL

Dissecting lub plab-hlwb dynamics hauv qab anorexia

Kev pub mis yog qhov tseem ceeb ntawm tus tsiaj ciaj sia, yog li nws tsis yog qhov xav tsis thoob tias lub plab thiab lub hlwb nyob hauv kev sib txuas lus tas li los tswj cov khoom noj kom tsim nyog thiab lub cev ruaj khov. Txawm li cas los xij, nyob rau hauv lub xub ntiag ntawm o, qhov system no yuav tawg. Ib qho ntawm cov cim tseem ceeb ntawm kev mob anorexia (tsis yog yuav tsum tsis meej pem nrog anorexia nervosa) yog qhov tsis qab los noj mov, uas tuaj yeem ua rau mob tsis txaus noj. Cov kev kho tam sim no - suav nrog IV-xa khoom noj khoom haus thiab plab hnyuv plab - tuaj yeem txo lub neej zoo thiab muaj txiaj ntsig tseem ceeb.

Dr. Beutler lub hom phiaj siv kev soj ntsuam neural siab heev thiab kev tswj xyuas cov txheej txheem los txiav cov txheej txheem hauv qab uas cuam tshuam nrog kev mob anorexia. Beutler's pab neeg yuav siv calcium imaging los qhia txog cov teebmeem ntawm ib tus neeg cytokines (cov cim qhia tawm thaum muaj mob) muaj rau cov pab pawg tshwj xeeb ntawm kev noj cov neurons. Nws pab pawg kuj tseem yuav siv cov cuab yeej cuab tam caj ces los sim hla qhov tsis tsim nyog 'tsis txhob noj' cov cim uas tshwm sim los ntawm qhov mob hnyav. Thaum kawg, nws yuav kawm seb cov qauv tshwj xeeb ntawm cov kab mob inflammatory hloov cov lus teb neural rau kev noj zaub mov zoo li cas.

Beutler txoj kev tshawb fawb yuav yog thawj zaug los kawm txog cov txheej txheem tshwj xeeb ntawm qib kev nthuav dav hauv cov kab mob muaj sia. Los ntawm kev txheeb xyuas lub hom phiaj ntawm lub paj hlwb ntawm cytokine tso tawm, thiab txiav txim siab yuav ua li cas qhov no modulates qab los noj mov, Beutler vam tias yuav txheeb xyuas cov hom phiaj kho mob rau kev noj zaub mov tsis txaus cuam tshuam nrog cov kab mob inflammatory. Tsis tas li ntawd, nws lub chaw kuaj mob lub hom phiaj los tsim ib txoj hauv kev ntawm lub plab-hlwb-kev tiv thaiv kab mob uas yuav muaj kev cuam tshuam loj tsis yog rau kev kho mob-kho anorexia, tab sis dav rau yav tom ntej noj thiab kev tshawb fawb metabolism.

Jeremy Day, Ph.D., Associate Professor, Department of Neurobiology, Heersink Tsev Kawm Ntawv ntawm Tshuaj, University of Alabama - Birmingham; thiab Ian Maze, Ph.D., Xib fwb – Departments of Neuroscience and Pharmacological Sciences, Director – Center for Neural Epigenome Engineering, Icahn School of Medicine ntawm Mount Sinai, New York City

Leveraging ib leeg-cell epigenomics rau tsom manipulation ntawm tshuaj-activated ensembles

Kev quav yeeb tshuaj yog ib qho teeb meem loj rau tib neeg thiab tib neeg tib neeg. Thaum muaj kev tshawb fawb tseem ceeb rau kev nkag siab thiab kho kev quav tshuaj, 60% ntawm cov neeg kho yuav raug kev mob rov qab. Qhov tseeb, qhov kev ntshaw rau cov tshuaj yuav nce ntxiv nyob rau lub sijhawm, incubating nyob rau hauv cov neeg uas tau quav yeeb tshuaj txawm tias tsis muaj tshuaj ntxiv. Dr. Hnub thiab Dr. Maze tsom rau kev tshawb fawb txog kev quav yeeb quav tshuaj ntawm qib tshiab - drilling mus rau epigenetic teebmeem ntawm kev siv yeeb tshuaj ntawm cov hlwb tshwj xeeb ntawm ib theem ntawm tes, thiab yuav ua li cas cov no tuaj yeem ua rau muaj kev rov qab los.

Cov kev tshawb fawb ua ntej tau pom tias kev raug tshuaj los ntawm lub sijhawm hloov pauv cov noob qhia li cas. Hauv cov ntsiab lus, cov tshuaj muaj peev xwm hijack genetic tswj cov ntsiab lus hu ua "enhancers," uas thaum qhib ua rau qee cov noob tau nthuav tawm hauv hlwb hlwb uas txhawb cov neeg nrhiav cov tshuaj no. Hnub thiab Maze tau tsim ib txoj haujlwm los txheeb xyuas cov kev txhim kho no hauv cov xovtooj ntawm tes tshwj xeeb uas tau ua haujlwm (lossis tsis nyob ntsiag to) los ntawm cov yeeb yaj kiab - nkag siab zoo thiab tshawb fawb cov tshuaj tiv thaiv - thiab tom qab ntawd tsim thiab ntxig cov kab mob kis mus rau hauv cov hlwb uas tsuas yog ua haujlwm hauv lub xub ntiag ntawm uas unsilenced enhancer. Siv lub tswv yim no, tus kab mob vector yuav nthuav qhia nws cov khoom thauj nkaus xwb hauv cov khoom siv ntawm tes uas cuam tshuam los ntawm cov yeeb yaj kiab thiab tso cai rau cov kws tshawb nrhiav optogenetically lossis chemogenetically qhib lossis deactivate cov hlwb cuam tshuam.

Nrog rau qhov no, Hnub thiab Maze yuav cuam tshuam cov pawg los tshawb xyuas lawv cov teebmeem ntawm kev nrhiav tshuaj yeeb hauv tus qauv nas ntawm kev tswj hwm tus kheej ntawm tus kheej. Lawv txoj haujlwm tsim los ntawm kev nce qib tsis ntev los no hauv kev muaj peev xwm los tsom rau ib tus neeg lub hlwb thiab cov pab pawg me ntawm cov hlwb, tsis yog tag nrho cov pejxeem ntawm cov hlwb lossis cov cell hom raws li tau ua kom pom tseeb ntawm kev tshawb fawb yav dhau los. Tam sim no nws muaj peev xwm tsom mus rau lub luag haujlwm tshwj xeeb ntawm cov hlwb ua si, kev cia siab yog tias cov kev kho mob zoo dua tuaj yeem tsim kho uas hais txog cov caj ces ntawm kev quav tshuaj thiab rov qab los, thiab tsis muaj kev cuam tshuam tsis zoo ntawm kev tswj cov neeg loj dua, tsis tshua muaj hom phiaj ntawm cov hlwb hlwb.

Stephan Lammel, Ph.D., Associate Professor of Neurobiology, University of California - Berkeley

Neurotensin kho cov kev cai ntawm hedonic noj tus cwj pwm thiab rog

Lub hlwb yog obsessed nrog nrhiav thiab noj zaub mov. Thaum pom cov zaub mov muaj calorie ntau - tsis tshua muaj hauv cov tsiaj qus - tsiaj txhu yuav noj nws sai sai. Rau tib neeg uas tau npaj nkag mus rau cov zaub mov muaj calorie ntau, qhov kev xav qee zaum ua rau muaj kev noj ntau dhau, rog, thiab muaj teeb meem kev noj qab haus huv. Tab sis kev tshawb fawb kuj tau pom tias qee zaum, kev tsav tsheb rau cov khoom noj uas muaj calorie ntau tuaj yeem txo qis thaum cov zaub mov zoo li no ib txwm muaj. Dr. Lammel nrhiav kev txheeb xyuas cov txheej txheem neural thiab cov cheeb tsam hauv lub hlwb uas cuam tshuam nrog kev noj zaub mov zoo li no thiab nws txoj cai.

Cov kev tshawb fawb xyoo dhau los tau txuas kev noj zaub mov rau lub hypothalamus, ib qho qub thiab tob ntawm lub hlwb. Txawm li cas los xij, cov pov thawj tseem qhia txog lub luag haujlwm rau qhov khoom plig thiab qhov chaw txaus siab ntawm lub hlwb. Lammel txoj kev tshawb fawb ua ntej pom tias kev sib txuas los ntawm lub lateral nucleus accumbens (NAcLat) mus rau ventral tegmental cheeb tsam (VTA) yog lub hauv paus rau kev noj zaub mov hedonistic - ua kom cov kev sib txuas ntawm optogenetically coj mus rau kev noj zaub mov muaj calorie ntau ntau, tab sis tsis yog zaub mov noj. Lwm qhov kev tshawb fawb tau txheeb xyuas cov amino acid neurotensin (NTS) ua tus neeg ua si hauv kev tswj hwm kev noj zaub mov, ntxiv rau lwm lub luag haujlwm.

Lammel txoj kev tshawb fawb nrhiav los qhia txog lub circuitry thiab lub luag hauj lwm ntawm ntau qhov chaw ntawm lub hlwb uas coj tsiaj mus noj hedonistically raws li zoo raws li lub luag hauj lwm ntawm NTS, uas yog qhia nyob rau hauv lub NAcLat. Cov ntsiab lus tau nthuav tawm nrog kev noj zaub mov zoo lossis kev noj zaub mov muaj calorie ntau ntau, thiab kev ua ub no ntawm NAcLat-to-VTA txoj hauv kev tau sau tseg thiab ua raws li kev coj noj coj ua. Nws kuj tseem yuav taug qab cov kev hloov pauv raws sijhawm nrog rau lub sijhawm ntev rau cov zaub mov hedonistic. Kev tshawb fawb ntxiv yuav saib cov kev hloov pauv hauv NTS muaj nyob hauv cov hlwb, thiab seb nws qhov muaj nyob hauv ntau npaum li cas cuam tshuam rau kev ua haujlwm ntawm tes. Los ntawm kev nkag siab txog txoj hauv kev thiab cov tshuab molecular uas cuam tshuam nrog kev noj zaub mov thiab kev rog rog, txoj haujlwm no yuav ua rau muaj kev mob siab rau yav tom ntej pab tswj kev rog.

Lindsay Schwarz, Ph.D., Assistant Professor in Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN

Txheeb xyuas lub hlwb circuits uas txuas ua pa thiab kev paub txog lub xeev

Ua pa tsis siv neeg hauv cov tsiaj, tab sis tsis zoo li lwm yam tseem ceeb hauv kev ua haujlwm - lub plawv dhia, kev zom zaub mov, thiab lwm yam - tsiaj muaj peev xwm tswj tau ua pa. Kev ua pa kuj tseem khi rau kev xav thiab lub siab lub ntsws nyob rau hauv ob txoj kev: kev xav ua rau muaj kev hloov pauv hauv kev ua pa, tab sis nco ntsoov hloov ua pa kuj tau pom tias muaj kev cuam tshuam rau lub siab. Hauv nws txoj kev tshawb fawb, Dr. Schwarz lub hom phiaj txhawm rau txheeb xyuas qhov ua tsis taus pa ntawm cov neurons tau xaiv los ntawm lub cev thiab kev txawj ntse thiab qhia cov cheeb tsam hauv hlwb uas lawv txuas nrog. Qhov kev tshawb fawb no tuaj yeem ua pov thawj pab tau rau hauv kev kawm ntau yam kab mob hauv lub paj hlwb uas ua rau ua pa cuam tshuam, xws li cov me nyuam mos tuag tam sim ntawd (SIDS), central pw tsaug zog apnea, thiab kev ntxhov siab.

Schwarz lub hom phiaj los ua kom zoo dua ntawm kev nce qib hauv neural tagging los kawm cov neurons uas, nyob tob rau hauv lub hlwb qia, ib txwm ua nyuaj rau kev cais thiab sau cia hauv vivo. Tab sis nrog kev ua si tagging, Schwarz tuaj yeem txheeb xyuas cov neurons tau qhib thaum lub sijhawm innate vs. nquag ua pa. Nyob rau yav tas los, cov neeg kawm tau ua rau muaj kev ntxhov siab uas ua rau lawv khov thiab hloov lawv ua pa. Cov kws tshawb nrhiav tuaj yeem tshuaj xyuas cov cim npe neurons txhawm rau txheeb xyuas qhov twg ua haujlwm hauv cov ntsiab lus, thiab hais txog seb cov no sib tshooj nrog cov neurons nquag thaum lub sijhawm ua pa.

Lub hom phiaj thib ob yog txhawm rau txheeb xyuas tus lej molecular ntawm kev ua pa ntsig txog neurons uas tau ua haujlwm thaum lub caij txias kom nkag siab meej dua tias cov hlwb twg yog ib feem ntawm lub tshuab ua pa. Thaum kawg, tau txheeb xyuas cov neurons, Schwarz yuav siv cov kab mob vector uas tsim los ntawm lwm tus kws tshawb fawb los txiav txim siab seb qhov twg ntawm lub hlwb cov hlwb txuas mus rau. Kev txheeb xyuas qhov sib txuas ntawm lub hlwb thiab ua pa, sib tshooj ntawm kev nco qab thiab tsis nco qab ua pa circuits, thiab kev sib txuas ntawm kev ua pa thiab qee yam kab mob tuaj yeem ua rau lub hauv paus rau kev kho kom zoo dua qub nrog rau kev nkag siab tag nrho ntawm peb txoj haujlwm tseem ceeb tshaj plaws yog siv li cas.

Ntsiab lus: Neurobiology ntawm Lub Hlwb Tsis Muaj Zog Cov Khoom Plig, McKnight Endowment Fund rau Neuroscience

Kaum Ob Hlis 2021

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