Grant: CIHR Fellowship
Centre hospitalier de l'Université de Montréal (CHUM)
$108,750.00
Investigating the Role of TDP-43 in Polyglutamine Toxicity
FY 2012-13
Summary
Mutations in TDP-43 (TAR DNA-binding Protein) and FUS (Fused in Sarcoma) have been identified in patients with Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia, while TDP-43 and FUS protein accumulations are observed in a growing number of neurodegenerative including Huntington's Disease (HD). My preliminary data shows that reducing TDP-43 and FUS activity rescues toxicity in worm and mammalian polyglutamine (polyQ) models. Based on my genetic analyses with worms the mechanism may rest with (1) Increased proteotoxic stress within the Endoplasmic Reticulum (ER) and/or (2) Inappropriate regulation of TDP-43/FUS target RNAs. I request support to investigate the molecular basis of TDP-43, FUS and huntingtin toxicity in primary neuronal culture from CAG140 knock-in mice.
Department
Program
CIHR Fellowship
Location
Quebec, Canada
Recipient Type
Not-for-profit organization or charity
Type
Grant
Source
CIHR Funding Decisions Database
As published
Id
269483
Name
Julien Carl
Region
Québec
Country
Canada
Orgtype
Institution Paid; Research Institution
Partnername
Huntington Society of Canada
Instname2
Neurosciences, Mental Health and Addiction
Theme2
Biomedical
Prcname2
Fellowships - Post-PhD
Projecttitle
Investigating the Role of TDP-43 in Polyglutamine Toxicity
Programtype2
Fellowship Programs
Orgnameinp2
Centre hospitalier de l'Université de Montréal (CHUM)
Cihramount2
$108,750
Cihrequipment2
$0
Programname2
CIHR Fellowship
Keyworddelim
Amyotrophic Lateral Sclerosis; Drug Screening; Exome Sequencing; Functional Studies; Gene Identification; Genetic Testing; Hereditary Spastic Paraplegia; Huntington'S Disease; Mutation Detection; Standardisation Of Diagnosis
Abstract
Mutations in TDP-43 (TAR DNA-binding Protein) and FUS (Fused in Sarcoma) have been identified in patients with Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia, while TDP-43 and FUS protein accumulations are observed in a growing number of neurodegenerative including Huntington's Disease (HD). My preliminary data shows that reducing TDP-43 and FUS activity rescues toxicity in worm and mammalian polyglutamine (polyQ) models. Based on my genetic analyses with worms the mechanism may rest with (1) Increased proteotoxic stress within the Endoplasmic Reticulum (ER) and/or (2) Inappropriate regulation of TDP-43/FUS target RNAs. I request support to investigate the molecular basis of TDP-43, FUS and huntingtin toxicity in primary neuronal culture from CAG140 knock-in mice.
Competitiondate
201210
Approvedterm2
2 yrs 5 mths
Pinamesdelim
Julien, Carl
Approvedterm
2 ans 5 mois
Cihrcontribution2
~ $108,750~ $0~
