Mechanotransduction C. elegans

NIH Pandemic-Era Grants

Pandemic Era Grants

2019

↗ Live URL (may be dead)

Document text

Principal Investigator: JOSHUA M KAPLAN
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2019
Award: $588,908
Funding agency: National Institute of Neurological Disorders and Stroke

   
DESCRIPTION (provided by applicant): The goal of this project is to identify cellular defects that are caused by mutations in genes linked to Autism spectrum disorders (ASD), using the C. elegans neuromuscular junction as a model. In particular, we will test two prominent models for pathophysiological mechanisms in ASD. First, we test the idea that ASD linked genes play a direct role in regulating activity induced gene expression. Second, we will determine if ASD linked genes alter the synaptic targeting of GABAA receptors, thereby altering inhibitory synaptic strength. A critical feature of the genetics of ASD is that mutations conferring risk are nearly always heterozygous in affected individuals, implying that the majority of ASD linked genes are dose sensitive. Thus, we will ask if activity-induced gene expression and synaptic targeting of GABAA receptors are sensitive to copy number variations in ASD linked genes. In addition to testing their potential importance in the pathophysiology of ASD, our Aims address basic mechanisms controlling nervous system development and function.

Terms: <Address><Adhesion Molecule><Affect><Autism><Autistic Disorder><Binding><Biochemical><Biophysics><C elegans><C. elegans><C.elegans><Caenorhabditis elegans><Calcium Channel><Calcium Channel Antagonist Receptor><Calcium Channel Blocker Receptors><Calcium Ion Channels><Cell Adhesion Molecule Gene><Cell Adhesion Molecules><Cell Communication and Signaling><Cell Signaling><Cell model><Cell-Extracellular Matrix><Cellular model><Cerebroatrophic Hyperammonemia><Cognitive><Copy Number Polymorphism><Data><Defect><Development><Developmental Delay><Developmental Delay Disorders><Diffuse><Dose><Down Syndrome><Down's Syndrome><Downs Syndrome><Dysfunction><ECM><Early Infantile Autism><Exhibits><Extracellular Matrix><Functional disorder><Funding><Gene Expression><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic defect><Goals><Immobilization><Individual><Infantile Autism><Inhibitory Synapse><Intracellular Communication and Signaling><Kanner's Syndrome><Knock-out><Knockout><LIN><Langdon Down syndrome><Link><Lobular Intraepithelial Neoplasia><Lobular Neoplasia><MEF-2><Mammalia><Mammals><Mediating><Mental disorders><Mental health disorders><Mice><Mice Mammals><Modeling><Molecular><Molecular Interaction><Mongolism><Murine><Mus><Mutation><Myoneural Junction><Neural Transmission><Neurodevelopmental Disorder><Neurological Development Disorder><Neuromuscular Junction><Patients><Pattern><Peptide Domain><Physiopathology><Play><Protein Domains><Proteins><Psychiatric Disease><Psychiatric Disorder><Receptor Protein><Recurrence><Recurrent><Rett Disorder><Rett Syndrome><Risk><Role><Scaffolding Protein><Schizophrenia><Schizophrenic Disorders><Signal Transduction><Signal Transduction Systems><Signaling><Specific Child Development Disorders><Synapses><Synaptic><Synaptic Transmission><Tertiary Protein Structure><Testing><Trisomy 21><VDCC><Voltage-Dependent Calcium Channels><autism spectrum disorder><autistic spectrum disorder><biochemical model><biological signal transduction><biophysical foundation><biophysical principles><biophysical sciences><cell adhesion protein><cholinergic><chromosome 21 trisomy syndrome><congenital acromicria syndrome><copy number variant><copy number variation><dementia praecox><developmental><experiment><experimental research><experimental study><ezrin><genome mutation><insight><mechanosensing><mechanotransduction><mef2 protein><membrane-organizing extension spike protein><mental illness><moesin><morbus Down><muscle-specific enhancer factor-2><myocyte enhancer factor 2><myocyte-specific enhancer-binding factor 2><nervous system development><neuroligin 1><neurotransmitter release><orthopedic freezing><pathophysiology><phosphoprotein p81><pseudohypertrophic progressive muscular dystrophy><psychiatric illness><psychological disorder><public health relevance><radixin><radixin protein><receptor><scaffold><scaffolding><schizophrenic><social role><synapse><synapse inhibition><synaptic inhibition><trisomy 21 syndrome>