- Genetics, Aging, and Longevity in Model Organisms
- Reproductive Biology and Fertility
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Circadian rhythm and melatonin
- RNA Research and Splicing
- Spaceflight effects on biology
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Nuclear Structure and Function
- Photosynthetic Processes and Mechanisms
- Sexual Differentiation and Disorders
- Animal Genetics and Reproduction
- Cell death mechanisms and regulation
- Parasite Biology and Host Interactions
- Nematode management and characterization studies
- Developmental Biology and Gene Regulation
- Muscle Physiology and Disorders
- Reproductive Health and Technologies
- Planarian Biology and Electrostimulation
- Sperm and Testicular Function
- Genomics and Chromatin Dynamics
- Insect Resistance and Genetics
- Demographic Trends and Gender Preferences
- SARS-CoV-2 and COVID-19 Research
Fred Hutch Cancer Center
2007-2023
University of Washington
2006-2021
Seattle University
1996-2017
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
1993-2016
Cancer Research Center
1996-2016
Howard Hughes Medical Institute
2002-2013
Amherst College
2002
University of Wisconsin–Madison
1998
MRC Laboratory of Molecular Biology
1986-1987
Medical Research Council
1987
Early embryonic cells in Caenorhabditis elegans embryos interact through a signaling pathway closely related to the Notch Drosophila and vertebrates.Components of this include ligand, receptor, presenilin proteins, novel protein, APH-2, that is Nicastrin protein humans. Here we identify aph-1 gene as new component elegans. predicted encode novel, highly conserved multipass membrane protein. We show genes share similar function they are both required for proper cell-surface localization...
During morphogenesis of the Caenorhabditis elegans embryo, hypodermal (or epidermal) cells migrate to enclose embryo in an epithelium and, subsequently, change shape coordinately elongate body (Priess, J.R., and D.I. Hirsh. 1986. Dev. Biol. 117:156– 173; Williams-Masson, E.M., A.N. Malik, J. Hardin. 1997. Development [Camb.]. 124:2889–2901). We have isolated mutants defective that identify three genes required for both cell migration during enclosure elongation. Analyses hmp-1, hmp-2, hmr-1...
ABSTRACT The generation of asymmetry in the one-cell embryo Caenorhabditis elegans is necessary to establish anterior-posterior axis and ensure proper identity early blastomeres. Maternal-effect lethal mutations with a partitioning defective phenotype (par) have identified several genes involved this process. We new gene, par-6, which acts conjunction other par properly localize cytoplasmic components embryo. phenotypes par-6 embryos include equal-sized blastomeres, improper localization P...
The intestinal cells of Caenorhabditis elegans embryos contain prominent, birefringent gut granules that we show are lysosome-related organelles. Gut labeled by lysosomal markers, and their formation is disrupted in depleted AP-3 subunits, VPS-16, VPS-41. We define a class granule loss (glo) mutants defective biogenesis. the glo-1 gene encodes predicted Rab GTPase localizes to intestine glo-4 possible GLO-1 guanine nucleotide exchange factor. These other glo genes homologous implicated...
ABSTRACT Germ cells arise during early C. elegans embryogenesis from an invariant sequence of asymmetric divisions that separate germ cell precursors somatic precursors. We show maternal-effect lethal mutations in the gene pos-1 cause to inappropriately adopt fates. During embryogenesis, mRNA and POS-1 protein are present predominantly is a novel with two copies CCCH finger motif previously described germline proteins PIE-1 MEX-1 elegans, mammalian TIS11/Nup475/TTP protein. However, several...
The endoderm in the nematode Caenorhabditis elegans is clonally derived from E founder cell. We identified a single genomic region (the endoderm-determining region, or EDR) that required for production of entire C. endoderm. In embryos lacking EDR, cell gives rise to ectoderm and mesoderm instead appears adopt fate its cousin, C end-1, gene restores EDR deficiency homozygotes. end-1 transcripts are first detectable specifically cell, consistent with direct role development. END-1 protein an...
ABSTRACT P granules are cytoplasmic structures of unknown function that associated with germ nuclei in the C. elegans gonad, and localized exclusively to cells, or cell precursors, throughout life cycle. All known protein components contain putative RNA- binding motifs, suggesting RNA is involved either structure granules. However, no specific mRNAs have been identified within gonad. We show here normally a low level RNA, describe conditions increase this level. present evidence several,...
Oocytes in the C. elegans gonad enlarge rapidly. During stage of enlargement, they are transcriptionally quiescent, and it is not understood how acquire large quantities materials such as mRNA protein. Enlarging oocytes connected via cytoplasmic bridges to a large, younger population active germ cells at various stages mitosis meiosis. We show here that there general streaming cytoplasm towards into enlarging oocytes, originating primarily from pachytene-stage cells. Because previous studies...
PAR proteins distribute asymmetrically across the anterior-posterior axis of 1-cell-stage C. elegans embryo, and function to establish subsequent asymmetries. By end 4-cell stage, anteriorly localized proteins, such as PAR-3 PAR-6, redistribute outer, apical surfaces cells, whereas posteriorly PAR-1 PAR-2, inner, basolateral surfaces. Because are provided maternally, distinguishing apicobasal from earlier functions requires a method that selectively prevents activity after 1-cell stage. In...
Germline-specific granules of unknown function are found in a wide variety organisms, including C. elegans, where they called P granules. cytoplasmic bodies oocytes and early embryos. Throughout most the elegans life cycle, however, associated with clusters nuclear pore complexes (NPCs) on germ cell nuclei. We show that perinuclear differ from many respects, structure, stability response to metabolic changes. Our results suggest nuclear-associated provide compartment newly exported mRNAs...
The molecular mechanisms that maintain totipotency of the germline are not well understood. Here, we show two conserved translational regulators, MEX-3 and GLD-1, essential for maintaining in Caenorhabditis elegans germline. In mex-3 gld-1 mutants, germ cells transdifferentiate into various somatic cell types such as muscles or neurons. Our findings implicate RNA regulation maintenance totipotency, suggest multiple at different stages development, establish a genetically tractable model...