- Invertebrate Immune Response Mechanisms
- Insect symbiosis and bacterial influences
- Neurobiology and Insect Physiology Research
- Antimicrobial Peptides and Activities
- Developmental Biology and Gene Regulation
- Chromosomal and Genetic Variations
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- DNA and Nucleic Acid Chemistry
- Immune Response and Inflammation
- Wnt/β-catenin signaling in development and cancer
- Genomics and Chromatin Dynamics
- Chemical Synthesis and Analysis
- Cellular Mechanics and Interactions
- DNA Repair Mechanisms
- Animal Genetics and Reproduction
- Microtubule and mitosis dynamics
- Amino Acid Enzymes and Metabolism
- Signaling Pathways in Disease
- Photopolymerization techniques and applications
- Enzyme Structure and Function
- Sperm and Testicular Function
- Cellular transport and secretion
- Aquaculture disease management and microbiota
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
University of California, San Diego
2003-2021
University of Chicago
2019
National Institutes of Health
2018
National Institute of Mental Health
2017
Brandeis University
2016
The University of Texas Southwestern Medical Center
1991-2002
University of California, Berkeley
1985-2002
Southwestern Medical Center
1993-1998
Sapienza University of Rome
1997
McMaster University
1993-1994
Sexual orientation and courtship behavior in Drosophila are regulated by fruitless (fru), the first gene a branch of sex-determination hierarchy functioning specifically central nervous system (CNS). The phenotypes new fru mutants encompass nearly all aspects male sexual behavior. Alternative splicing transcripts produces sex-specific proteins belonging to BTB-ZF family transcriptional regulators. products produced only about 500 105 neurons that comprise CNS. properties expressing these...
ABSTRACT We show that the Drosophila gene diaphanous is required for cytokinesis. Males homozygous dia1 mutation are sterile due to a defect in cytokinesis germline. Females trans-heterozygous and deficiency lay eggs with defective eggshells; failure of observed follicle cell layer. Null alleles lethal. Death occurs at onset pupation absence imaginal discs. Mitotic figures larval neuroblasts were found be polyploid, apparently The predicted 123×103Mr protein contains two domains shared by...
The internal state of an organism influences its perception attractive or aversive stimuli and thus promotes adaptive behaviors that increase likelihood survival. mechanisms underlying these perceptual shifts are critical to our understanding how neural circuits support animal cognition behavior. Starved flies exhibit enhanced sensitivity odors reduced odors. Here, we show a functional remodeling the olfactory map is mediated by two parallel neuromodulatory systems act in opposing directions...
Abstract We describe 83 recessive autosomal male-sterile mutations, generated by single P element mutagenesis in Drosophila melanogaster. Each mutation has been localized to a lettered subdivision of the polytene map. Reversion analyses, as well complementation tests using available chromosomal deficiencies, indicate that insertions are responsible for mutant phenotypes. These mutations represent 63 groups, 58 which required spermatogenesis. Phenotypes spermatogenesis mutants were analyzed...
Stimulation of the type 1 IL-1R (IL-1R1) and IL-18R by their cognate ligands induces recruitment IL-1R-associated kinase (IRAK). Activation IRAK leads in turn to nuclear translocation NF-kappaB, which directs expression innate adaptive immune response genes. To study function cytokine signaling, we generated cells mice lacking protein. IRAK-deficient fibroblasts show diminished activation NF-kappaB when stimulated with IL-1. Immune effector without exhibit a defective IFN-gamma costimulation...
ABSTRACT We have identified a localized RNA component of Xenopus germ plasm. This RNA, Xdazl (Xenopus DAZ-like), encodes protein homologous to human DAZ (Deleted in Azoospermia), vertebrate DAZL and Drosophila Boule proteins. Human males deficient few or no sperm boule mutant flies exhibit complete azoospermia male sterility. was detected the mitochondrial cloud vegetal cortex oocytes. In early embryos, exclusively Consistent with other organisms, also expressed spermatogonia spermatocytes...
The mechanism of site-specific genetic recombination mediated by Tn3 resolvase has been investigated a topological approach. Extrapolation detailed model synapsis and strand exchange predicts the formation an additional DNA product with specific knotted structure. Two-dimensional gel electrophoresis reacted in vitro revealed product, about 0.1 percent total, appropriate mobility. A technique for determining topology electron microscopy was improved such that less than nanogram required....
The molecular circuitry underlying innate immunity is constructed of multiple, evolutionarily conserved signaling modules with distinct regulatory targets. MAP kinases and the IKK-NF-κB molecules play important roles in initiation immune effector responses. We have found that Drosophila NF-κB protein Relish plays a crucial role limiting duration JNK activation output response to Gram-negative infections. linked proteasomal degradation TAK1, upstream kinase required for activation....
In Drosophila melanogaster, recognition of an invading pathogen activates the Toll or Imd signaling pathway, triggering robust upregulation innate immune effectors. Although mechanisms and are now well understood, functions immune-induced transcriptome proteome remain much less characterized. Through bioinformatic analysis effector gene sequences, we have defined a family twelve genes – Bomanins (Boms) that specifically induced by encode small, secreted peptides unknown biochemical activity....
ABSTRACT The Drosophila Formin Homology (FH) protein Diaphanous has an essential role during cytokinesis. To gain insight into the function of cytokinesis and explore its in other processes, we generated embryos deficient for analyzed three cell-cycle-regulated actin-mediated events embryogenesis: formation metaphase furrow, cellularization pole cells. In dia embryos, all processes are defective. Actin filaments do not organize properly to furrows actin ring is absent from base presumptive...
Signaling from the transmembrane receptor Toll to Rel-related transcription factors regulates dorsoventral patterning of Drosophila embryo, as well larval and adult immunity. To identify additional pathway components, we have used double-stranded RNA interference investigate counterparts genes that regulate mammalian Rel family member NF-κB. Experiments in cultured cells reveal fly orthologue adaptor protein MyD88 is essential for signal transduction a second protein, Tube. By using...
Body shape determination represents a critical aspect of morphogenesis. In the course investigating body regulation in Drosophila, we have identified dominant mutation, TweedleD(1) (TwdlD(1)), that alters overall dimensions at larval and pupal stages. Characterization affected locus led to discovery gene family has 27 members Drosophila is found only among insects. Analysis expression RNA protein levels revealed gene-specific temporal spatial patterns ectodermally derived tissues. addition,...
The Bomanins (Boms) are a family of dozen secreted peptides that mediate the innate immune response governed by <i>Drosophila</i> Toll receptor. We recently showed deleting cluster 10 <i>Bom</i> genes blocks Toll-mediated defenses against range fungi and gram-positive bacteria. Here, we characterize activity individual Bom members. provide evidence Boms overlap in function single gene encoding mature peptide just 16 amino acids can act largely or entirely independent...
Fungal infections, widespread throughout the world, affect a broad range of life forms, including agriculturally relevant plants, humans, and insects. In defending against fungal fruit fly Drosophila melanogaster employs Toll pathway to induce large number immune peptides. Some have been investigated, such as antimicrobial peptides (AMPs) Bomanins (Boms); many, however, remain uncharacterized. Here, we examine role in innate immunity two related peptides, Daisho1 Daisho2 (formerly IM4 IM14,...
The fruit fly Drosophila melanogaster combats microbial infection by producing a battery of effector peptides that are secreted into the haemolymph. Technical difficulties prevented investigation these short genes until recent advent CRISPR/CAS era. As consequence, many putative immune effectors remain to be formally described, and exactly how each contribute survival is not well characterized. Here we describe novel antifungal peptide gene name Baramicin A . We show BaraA encodes precursor...
Abstract Cecropins are small helical secreted peptides with antimicrobial activity that widely distributed among insects. Genes encoding strongly induced upon infection, pointing to their role in host defense. In Drosophila, four cecropin genes clustered the genome (CecA1, CecA2, CecB, and CecC) expressed infection downstream of Toll Imd pathways. this study, we generated a short deletion ΔCecA-C removing whole locus. Using deficiency alone or combination other peptide (AMP) mutations,...