A5073102971- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Molecular Biology Techniques and Applications
- Evolution and Genetic Dynamics
- Circadian rhythm and melatonin
- Reproductive Biology and Fertility
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Evolutionary Algorithms and Applications
- Animal Genetics and Reproduction
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- Muscle Physiology and Disorders
- Advanced Statistical Methods and Models
- Spaceflight effects on biology
- Fungal and yeast genetics research
- Computational Geometry and Mesh Generation
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
- Plant Molecular Biology Research
- Cellular Mechanics and Interactions
- Geological Modeling and Analysis
- Genetics, Bioinformatics, and Biomedical Research
Miami University
2025
University of Wyoming
2015-2024
Wyoming Department of Education
2022
Cornell University
2018
Plant (United States)
2018
University of Colorado Boulder
1998-2002
Howard Hughes Medical Institute
2000-2002
Yale University
1991-1998
Buffalo General Medical Center
1989-1996
Riverside Methodist Hospital
1979
The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints that prevent cell division in cells with damaged or incompletely replicated DNA. Rad9 was phosphorylated response to DNA damage, and interacted the COOH-terminal forkhead homology–associated (FHA) domain Rad53. Inactivation this abolished damage–dependent phosphorylation, G 2 /M cycle phase arrest, increase RNR3 transcription but did not affect replication inhibition–dependent phosphorylation. Thus, integrates...
SPK1/RAD53/MEC2/SAD1 of Saccharomyces cerevisiae encodes an essential protein kinase that is required for activation replication-sensitive and DNA damage-sensitive checkpoint arrest. We have investigated the regulation phosphorylation activity Spk1p during cell cycle by conditions activate pathways. Phosphorylation induced treatment cells with agents damage or interfere synthesis. Although only S- G2-phase cdc mutants arrest hyperphosphorylated Spk1p, damage-induced can occur in G1 M as...
Abstract: Transgenic Caenorhabditis elegans animals have been engineered to express wild‐type and single‐amino acid variants of a long form human β‐amyloid peptide (Aβ 1–42). These high levels (∼300 ng Aβ/mg total protein) apparently full‐length peptide, as determined by quantitative immunoblot. Expression Aβ in these leads rapid production amyloid deposits reactive with Congo red thioflavin S. This model system has used examine the effect Leu 17 Pro, Val, Ala 30 ‐Pro, Met 35 Cys,...
We report here a synthetic-lethal screen in Caenorhabditis elegans that overcomes number of obstacles associated with the analysis functionally redundant genes. Using this approach, we have identified mutations synthetically interact lin-35/Rb, SynMuv gene and sole member Rb/pocket protein family C. elegans. Unlike original screens, our approach is completely nonbiased can theoretically be applied to any situation which mutation fails produce detectable phenotype. From fzr-1, interacts...
During development, biomechanical forces contour the body and provide shape to internal organs. Using genetic molecular approaches in combination with a FRET-based tension sensor, we characterized pulling force exerted by elongating pharynx (foregut) on anterior epidermis during C. elegans embryogenesis. Resistance of this actomyosin-based circumferential constricting is mediated FBN-1, ZP domain protein related vertebrate fibrillins. fbn-1 was required specifically within FBN-1 expressed...
SPK1 was originally discovered in an immunoscreen for tyrosine-protein kinases Saccharomyces cerevisiae. We have used biochemical and genetic techniques to investigate the function of this gene its encoded protein. Hybridization probe ordered genomic library showed that is adjacent PEP4 (chromosome XVI L). Sporulation spk1/+ heterozygotes gave rise spk1 spores grew into microcolonies but could not be further propagated. These colonies were greatly enriched budded cells, especially those with...
Endocytosis, the process by which cells internalize plasma membrane and associated cargo, is regulated extensively posttranslational modifications. Previous studies suggested potential involvement of scores protein kinases in endocytic control, only a few have been validated vivo. Here we show that conserved NIMA-related NEKL-2/NEK8/9 NEKL-3/NEK6/7 (the NEKLs) control clathrin-mediated endocytosis C. elegans. Loss NEKL-2 or NEKL-3 activities leads to penetrant larval molting defects abnormal...
Background: Pancreatic cancer is the most lethal of all human cancers. The disease has no obvious symptoms in its early stages and majority cases, goes undetected until it advanced to point that surgery longer a viable option or metastasized other organs. absence reliable sensitive biomarkers for detection pancreatic contributes poor ability detect before progresses an untreatable stage. Objectives: Here, orthotopic xenograft mouse model was investigated determine if urinary metabolic could...
ABSTRACT We have identified strong loss-of-function mutations in the C. elegans cyclin E gene, cye-1. Mutations cye-1 lead to underproliferation of many postembryonic blast lineages as well defects fertility and gut-cell endoreduplication. In addition, is required maternally, but not zygotically for embryonic development. Our analysis vulval development mutants suggests that a timing mechanism may control onset cell terminal differentiation: once induced, these cells appear differentiate...
The beta gamma subunits of G-proteins are composed closely related 35 and 36 tightly associated with diverse 6-10 kDa subunits. We have developed a reconstitution assay using rhodopsin-catalyzed guanosine 5'-3-O-(thio)triphosphate (GTP S) binding to resolved alpha subunit the retinal G-protein transducin (Gt alpha) quantitate activity proteins. Rhodopsin facilitates exchange GTP S for GDP bound Gt 60-fold higher apparent affinity than alone. At limiting rhodopsin, G-protein-derived...
Human NIMA-related kinases have primarily been studied for their roles in cell cycle progression (NEK1/2/6/7/9), checkpoint–DNA-damage control (NEK1/2/4/5/10/11), and ciliogenesis (NEK1/4/8). We previously showed that Caenorhabditis elegans NEKL-2 (NEK8/9 homolog) NEKL-3 (NEK6/7 regulate apical clathrin-mediated endocytosis (CME) the worm epidermis are essential molting. Here we show also distinct controlling endosome function morphology. Specifically, loss of led to enlarged early endosomes...
Whole-genome sequencing (WGS) is an indispensable tool for identifying causal mutations obtained from genetic screens. To reduce the number of mutation candidates typically uncovered by WGS, Caenorhabditis elegans researchers have developed several strategies. One involves crossing N2-background mutants to polymorphic Hawaiian (HA) strain, which can be used simultaneously identify mutant strain variants and obtain high-density mapping information. This approach, however, not well suited...
Molting is an essential process in the nematode Caenorhabditis elegans during which epidermal apical extracellular matrix, termed cuticle, detached and replaced at each larval stage. The conserved NIMA-related kinases NEKL-2/NEK8/NEK9 NEKL-3/NEK6/NEK7, together with their ankyrin repeat partners, MLT-2/ANKS6, MLT-3/ANKS3, MLT-4/INVS, are for normal molting. In nekl mlt mutants, old cuticle fails to be completely shed, leading entrapment growth arrest. To better understand molecular cellular...
Significance Ubiquitination—the covalent attachment of ubiquitin to substrates—is a posttranslational modification that regulates virtually every aspect cellular function in eukaryotes. The final step substrate ubiquitination requires the coordination two types enzymes: ubiquitin-conjugating enzymes (E2s) and ligases (E3s). Whereas E3s can with different E2s, between has been reported only for same class. Here we show distinct E2/E3 pairs (UBC-18/ARI-1 UBC-3/CUL-1) coordinate ubiquitinate...