A5013229927- Genetics, Aging, and Longevity in Model Organisms
- Evolution and Genetic Dynamics
- CRISPR and Genetic Engineering
- Genetic Mapping and Diversity in Plants and Animals
- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- Parasite Biology and Host Interactions
- Parasites and Host Interactions
- Mitochondrial Function and Pathology
- Insect and Arachnid Ecology and Behavior
- Bioinformatics and Genomic Networks
- Metabolism and Genetic Disorders
- Microbial Metabolic Engineering and Bioproduction
- Fungal and yeast genetics research
- Cancer therapeutics and mechanisms
- Plant Micronutrient Interactions and Effects
- Helminth infection and control
- Genetic and phenotypic traits in livestock
- Insect Utilization and Effects
- Trace Elements in Health
- Microtubule and mitosis dynamics
- Animal Ecology and Behavior Studies
- DNA Repair Mechanisms
- Cancer Treatment and Pharmacology
- Nematode management and characterization studies
University of California, Los Angeles
2020-2024
Howard Hughes Medical Institute
2020-2024
Northwestern University
2016-2023
Molecular Sciences Institute
2013-2016
Studies in model organisms have yielded considerable insights into the etiology of disease and our understanding evolutionary processes. Caenorhabditis elegans is among most powerful used to understand biology. However, C. not as extensively other investigate how natural variation shapes traits, especially through use genome-wide association (GWA) analyses. Here, we introduce a new platform, Natural Diversity Resource (CeNDR) enable statistical genetics genomics studies connect results human...
Telomeres are involved in the maintenance of chromosomes and prevention genome instability. Despite this central importance, significant variation telomere length has been observed a variety organisms. The genetic determinants telomere-length their effects on organismal fitness largely unexplored. Here, we describe natural across Caenorhabditis elegans species. We identify large-effect variant that contributes to differences length. alters conserved oligonucleotide/oligosaccharide-binding...
Hawaiian isolates of the nematode species Caenorhabditis elegans have long been known to harbor genetic diversity greater than rest worldwide population, but this observation was supported by only a small number wild strains. To better characterize niche and C. other species, we sampled different substrates niches across islands. We identified hundreds new strains from oiwi. are found in cooler climates at high elevations not associated with any specific substrate, as compared species....
Benzimidazoles (BZ) are essential components of the limited chemotherapeutic arsenal available to control global burden parasitic nematodes. The emerging threat BZ resistance among multiple nematode species necessitates development novel strategies identify genetic and molecular mechanisms underlying this resistance. All detection helminth is focused on genotyping three variant sites in orthologs β-tubulin gene found confer free-living Caenorhabditis elegans. Because limitations laboratory...
Transposons are mobile DNA elements that generate both adaptive and deleterious phenotypic variation thereby driving genome evolution. For these reasons, genomes have mechanisms to regulate transposable element (TE) activity. Approximately 12-16% of the Caenorhabditis elegans is composed TEs, which majority likely inactive. However, most studies TE activity been conducted in laboratory strain N2, limits our knowledge effects across natural populations. We analyzed distribution abundance TEs...
Many chemotherapeutic drugs are differentially effective from one patient to the next. Understanding causes of this variability is a critical step towards development personalized treatments and improvements existing medications. Here, we investigate sensitivity group anti-neoplastic that target topoisomerase II using model organism Caenorhabditis elegans. We show wild strains C. elegans vary in their these drugs, use an unbiased genetic approach demonstrate natural variation explained by...
Parasitic nematodes impose a debilitating health and economic burden across much of the world. Nematode resistance to anthelmintic drugs threatens parasite control efforts in both human veterinary medicine. Despite this threat, genetic landscape potential mechanisms these critical remains largely unexplored. Here, we exploit natural variation model Caenorhabditis elegans briggsae discover quantitative trait loci (QTL) that sensitivity benzimidazoles widely used animal High-throughput...
We find that variation in the dbt-1 gene underlies natural differences Caenorhabditis elegans responses to toxin arsenic. This encodes E2 subunit of branched-chain α-keto acid dehydrogenase (BCKDH) complex, a core component amino (BCAA) metabolism. causally linked non-synonymous variant conserved lipoyl domain DBT-1 differential arsenic responses. Using targeted metabolomics and chemical supplementation, we demonstrate are caused by iso-branched chain fatty acids. Additionally, show levels...
Quantitative genetics in Caenorhabditis elegans seeks to identify naturally segregating genetic variants that underlie complex traits. Genome-wide association studies scan the genome for individual are significantly correlated with phenotypic variation a population, or quantitative trait loci. popular choice analyses because loci discovered segregate natural populations. Despite numerous successful mapping experiments, empirical performance of genome-wide study has not, date, been formally...
Phoresy is a widespread form of commensalism that facilitates dispersal one species through an association with more mobile second species. Dauer larvae the nematode Caenorhabditis elegans exhibit phoretic behavior called nictation, which could enable interactions animals such as isopods or snails. Here, we show natural C. isolates differ in nictation. We use quantitative behavioral assays and linkage mapping to identify genetic locus (nict-1) mediates interaction terrestrial isopods. The...
In budding yeast, targeting of active genes to the nuclear pore complex (NPC) and interchromosomal clustering is mediated by transcription factor (TF) binding sites in gene promoters. For example, for TFs Put3, Ste12, Gcn4 are necessary sufficient promote positioning at periphery clustering. However, all three cases, regulated. Under uninducing conditions, local recruitment Rpd3(L) histone deacetylase transcriptional repressors blocks Put3 DNA binding. This a general function yeast...
Abstract Bleomycin is a powerful chemotherapeutic drug used to treat variety of cancers. However, individual patients vary in their responses bleomycin. The identification genetic differences that underlie this response variation could improve treatment outcomes by tailoring bleomycin dosages each patient. We the model organism Caenorhabditis elegans identify determinants bleomycin-response performing linkage mapping on recombinants derived from cross between laboratory strain (N2) and wild...
Genetic regulation of gene expression underlies variation in disease risk and other complex traits. The effect quantitative trait loci (eQTLs) varies across cell types; however, the complexity mammalian tissues makes studying cell-type eQTLs highly challenging. We developed a novel approach model nematode Caenorhabditis elegans that uses single-cell RNA sequencing to map at cellular resolution single one-pot experiment. mapped types an extremely large population genetically distinct C....
Recent work has provided strong empirical support for the classic polygenic model trait variation. Population-based findings suggest that most regions of genome harbor variation affecting traits. Here, we use approach experimental genetics to show that, indeed, genomic carry variants with detectable effects on growth and reproduction in Caenorhabditis elegans populations sensitized by nickel stress. Nine 15 adjacent intervals X chromosome, each encompassing ∼0.001 genome, have significant...
Abstract The diversity in sperm shape and size represents a powerful paradigm to understand how selection drives the evolutionary diversification of cell morphology. Experimental work on biology male-hermaphrodite nematode Caenorhabditis elegans has elucidated diverse factors important for fertilization success, including competitive superiority larger sperm. Yet despite extensive research, molecular mechanisms regulating C. genetic basis underlying natural variation remain unknown. To...
Zinc is an essential trace element that acts as a co-factor for many enzymes and transcription factors required cellular growth development. Altering intracellular zinc levels can produce dramatic effects ranging from cell proliferation to death. To avoid such fates, cells have evolved mechanisms handle both excess deficiency of zinc. homeostasis largely maintained via transporters, permeable channels, other zinc-binding proteins. Variation in these proteins might affect their ability...
Abstract The distribution of fitness effects (DFE) for new mutations is one the most theoretically important but difficult to estimate properties in population genetics. A crucial challenge inferring DFE from natural genetic variation sensitivity site frequency spectrum factors like size change, substructure, genome structure, and nonrandom mating. Although inference methods aim control changes, influence mating remains incompletely understood, despite being a common feature many species. We...
The nematode Caenorhabditis elegans is among the most widely studied organisms, but relatively little known about its natural ecology. Genetic diversity low across much of globe high in Hawaiian Islands and Pacific Rim. To characterize niche genetic C. on to explore how might be influenced by local adaptation, we repeatedly sampled nematodes over a three-year period, measured various environmental parameters at each sampling site, whole-genome sequenced isolates that identified. We found...
Toxin-antidote elements (TAs) are selfish DNA sequences that bias their transmission to the next generation. TAs typically consist of two linked genes: a toxin and an antidote. The kills progeny do not inherit TA, while antidote counteracts in TA. We previously discovered
Mutations in human metabolic genes can lead to rare diseases known as inborn errors of metabolism. For instance, patients with loss-of-function mutations either subunit propionyl-CoA carboxylase suffer from propionic acidemia because they cannot catabolize propionate, leading its harmful accumulation. Both the penetrance and expressivity disorders be modulated by genetic background. However, modifiers these are difficult identify lack statistical power for genetics. Here, we use a model...
Abstract Across diverse taxa, selfing species have evolved independently from outcrossing thousands of times. The transition to significantly decreases the effective population size, recombination rate, and heterozygosity within a species. These changes lead reduction in genetic diversity, therefore adaptive potential, by intensifying effects random drift linked selection. Within nematode genus Caenorhabditis , has at least three times all species, including model organism elegans show...