A5081867384- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Birth, Development, and Health
- Adipose Tissue and Metabolism
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Hereditary Neurological Disorders
- Nuclear Structure and Function
- Circadian rhythm and melatonin
- Neuroendocrine regulation and behavior
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA regulation and disease
- Cellular Mechanics and Interactions
- Biotechnology and Related Fields
- FOXO transcription factor regulation
- Genetic Neurodegenerative Diseases
- Pluripotent Stem Cells Research
- Genomics and Rare Diseases
- Amyotrophic Lateral Sclerosis Research
- Lipid metabolism and biosynthesis
- Cholinesterase and Neurodegenerative Diseases
- Prion Diseases and Protein Misfolding
- Advanced Biosensing Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
Washington State University
2006-2015
Harvard University Press
2012
Deseret Laboratories (United States)
2012
Harvard University
2010
Delta-9 desaturases, also known as stearoyl-CoA are lipogenic enzymes responsible for the generation of vital components membranes and energy storage molecules. We have identified a novel nuclear hormone receptor, NHR-80, that regulates delta-9 desaturase gene expression in Caenorhabditis elegans. Here we describe fatty acid compositions, lifespans, studies strains carrying mutations nhr-80 three genes encoding fat-5, fat-6, fat-7. The single mutants display only subtle changes composition...
Monounsaturated fatty acids are essential components of membrane and storage lipids. Their synthesis depends on the conversion saturated to unsaturated by Delta9 desaturases. Caenorhabditis elegans has three desaturases encoded genes fat-5, fat-6, fat-7. We generated nematodes that display a range altered acid compositions constructing double-mutant strains combine mutations in All combinations have reduced survival at low temperatures. The fat-5;fat-6 double mutants relatively subtle...
Transcription factors are key components of regulatory networks that control development, as well the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans permits global identification binding sites for transcription using chromatin immunoprecipitation and deep sequencing. describe validate this strategy, apply it factor PHA-4, which plays critical roles organ development other cellular processes. identified thousands PHA-4 during...
Ether lipids are widespread in nature, and they structurally functionally important components of membranes. The roundworm, Caenorhabditis elegans, synthesizes numerous lipid species containing alkyl alkenyl ether bonds. We isolated C. elegans strains carrying loss-of-function mutations three genes encoding the proteins required for initial steps biosynthetic pathway, FARD-1/FAR1, ACL-7/GNPAT, ADS-1/AGPS. Analysis mutant show that lack lipids, but possess ability to alter their composition...
<title>Abstract</title> Advances in genomic medicine have accelerated the identification of mutations disease- associated genes, but pathogenicity many remains unknown, hindering their use diagnostics and clinical decision-making. Predictive AI models been generated to combat this issue, current tools display low accuracy when tested against functionally validated datasets. We show that integrating detailed conformational data extracted from molecular dynamics simulations (MDS) into advanced...
Striated muscle laminopathies caused by missense mutations in the nuclear lamin gene LMNA are characterized cardiac dysfunction and often skeletal defects. Attempts to predict which variants pathogenic understand their physiological effects lag behind variant discovery. We created Caenorhabditis elegans models for striated introducing human of unknown significance at conserved residues within lmn-1 gene. Severe reduced fertility and/or motility C. elegans. Nuclear morphology defects were...
Clinical variants of TARDBP are associated with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and other degenerative diseases. The predicted C. elegans ortholog is encoded by tdp-1 , but functional orthology has not been demonstrated in vivo. We undertook CRISPR/Cas9-based genome editing the locus to create a complete loss function allele; all exons introns were deleted, creating tdp-1(tgx58) which resulted neurodegeneration after oxidative stress. Next, we CRISPR-based...
ABSTRACT Hereditary spastic paraplegia (HSP) is a group of degenerative neurological disorders. We identified variant in human kinesin light chain 4 (KLC4) that suspected to be associated with autosomal-dominant HSP. How this and other variants relate pathologies unknown. created humanized Caenorhabditis elegans model which klc-2 was replaced by KLC4 (referred as hKLC4) assessed the extent hKLC4 retained function worm. observed slight decrease motility but no nuclear migration defects worms,...
Polycyclic aromatic hydrocarbons (PAHs), in particular benzo [a]pyrene (BaP), have been identified as carcinogenic components of tobacco smoke. In mammals, the toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1), a pathway which absent Caenorhabditis elegans. contrast, worms prominently CYP-35 enzyme family seems be induced after BaP exposure. C. elegans, exposure reduces accumulation lysosomal neutral lipids dose dependent manner and deletion cyp-35A2 results...
Whole genome sequencing is rapidly being adopted in the clinic and resulting data deposition into ClinVar database quickly expanding. Especially impacted are Variants of Uncertain Significance (VUS), which growing exponentially, while remaining categories Pathogenic, Likely Benign, Benign show a small (linear) yearly increase. The result unactionable VUS forecast to take over by end decade. clinician may see variant their patient, but after cross reference ClinVar, they often do not obtain...
Hereditary spastic paraplegia (HSP) is a group of degenerative neurological disorders. We identified variant in human kinesin light chain
Abstract Purpose Functional evidence is a pillar of variant interpretation according to ACMG guidelines. can be obtained in variety models and assay systems, including patient-derived tissues iPSCs, vitro cellular assays, vivo assays. Here we evaluate the reliability practicality small animal model, C . elegans , through series experiments evaluating function syntaxin binding protein, STXBP1, well-known causative gene for Early infantile epileptic encephalopathy 1 (EIEE1). Methods Using...
To study important genes involved in Frontotemporal Dementia ( MAPT , GRN and C9orf72 ), we created deletion alleles the three orthologous ptl-1 pgrn-1 alfa-1 ). Simultaneously, replaced C. elegans gene with predicted human gene, often called whole-gene humanization, which allows direct assessment of conserved function, as well opportunity to examine consequences clinical disease-associated patient variations. Each was manipulated using a different selection strategy, including novel...
Neuronal FMRFamide signaling transmits social cues to modulate maternal provisioning of translational machinery.
Atropine has been used as an established anticonvulsant treatment for nerve agent intoxication. reduces electroshock recovery time among aldicarb-exposed wild-type C. elegans .
Abstract Striated muscle laminopathies caused by missense mutations in the nuclear lamin gene LMNA are characterized cardiac dysfunction and often skeletal defects. Attempts to predict which variants pathogenic understand their physiological effects lags behind variant discovery. We created Caenorhabditis elegans models for striated introducing human of unknown significance at conserved residues within lmn-1 gene. Severe reduced fertility and/or motility C. . Nuclear morphology defects were...
Our group studies organ formation using a simple organ, the C. elegans foregut (or pharynx), that nonetheless faces same hurdles confront organs in more complicated animals. main focus is transcriptional processes establish from pool of developmentally‐plastic precursors. I will discuss two aspects organogenesis: Pluripotency and cell‐fate acquisition . Early embryonic cells are born pluripotent, but over time their developmental choices become restricted. We study mediate transition...
Unsaturated fatty acids are a key component of triacylglycerides as well necessary constituents membrane phospholipids. The synthesis unsaturated in C. elegans depends on the activity family stearoyl-CoA desaturases (SCDs), encoded by fat-5, fat-6, and fat-7 genes. To determine role these we have characterized mutants that knockout three SCD Single show only subtle acid composition changes no obvious effects growth or reproduction, while triple mutant is lethal, demonstrating essential for...
ABSTRACT Mothers contribute cytoplasmic components to their progeny in a process called maternal provisioning. Provisioning is influenced by the parental environment, but molecular pathways that transmit environmental cues from mother are not well understood. Here we show C. elegans , social modulate provisioning regulate gene silencing offspring. Intergenerational signal transmission depends on pheromone-sensing neuron and neuronal FMRF (Phe-Met-Arg-Phe)-like peptides. Parental signaling...