A5014701962- RNA Research and Splicing
- RNA modifications and cancer
- Biochemical and Molecular Research
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Fungal and yeast genetics research
- Developmental Biology and Gene Regulation
- Signaling Pathways in Disease
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Enzyme Structure and Function
- Asthma and respiratory diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Toxin Mechanisms and Immunotoxins
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- IL-33, ST2, and ILC Pathways
- Planarian Biology and Electrostimulation
- Quinazolinone synthesis and applications
- Marine Ecology and Invasive Species
- Amyotrophic Lateral Sclerosis Research
- 14-3-3 protein interactions
- Nuclear Structure and Function
- Connective tissue disorders research
- Exercise and Physiological Responses
University of California, San Diego
2006-2024
Howard Hughes Medical Institute
2006-2020
Marine Biological Laboratory
2019-2020
Universities of Giessen and Marburg Lung Center
2015
German Center for Lung Research
2015
Computational Physics (United States)
2009
Department of Embryology
2002-2006
Carnegie Institution for Science
2002-2006
Carnegie Observatories
2003-2006
University of California, San Francisco
2000
Abstract Metazoan physiology depends on intricate patterns of gene expression that remain poorly known. Using transposon mutagenesis in Drosophila, we constructed a library 7404 protein trap and enhancer lines, the Carnegie collection, to facilitate mapping at single-cell resolution. By sequencing genomic insertion sites, determining splicing downstream enhanced green fluorescent (EGFP) exon, analyzing ovary salivary gland, found 600–900 different genes are trapped our collection. A core set...
Asymmetric localization of proteins plays a key role in many cellular processes, including cell polarity and fate determination. Using DNA microarray analysis, we identified plasma membrane protein-encoding mRNA (IST2) that is transported to the bud tip by an actomyosin-based process. created higher concentration IST2 protein compared with mother cell, this asymmetry was maintained septin-mediated diffusion barrier at mother-bud neck. These results indicate yeast creates distinct...
The discovery of large supramolecular complexes such as the purinosome suggests that subcellular organization is central to enzyme regulation. A screen yeast GFP strain collection identify proteins assemble into visible structures identified four novel filament systems comprised glutamate synthase, guanosine diphosphate-mannose pyrophosphorylase, cytidine triphosphate (CTP) or subunits eIF2/2B translation factor complex. Recruitment CTP synthase filaments and foci can be modulated by...
The Balbiani body or mitochondrial cloud is a large distinctive organelle aggregate found in developing oocytes of many species, but its presence the mouse has been controversial. Using confocal and electron microscopy, we report that does arise neonatal germline cysts primordial follicles disperses as begin to grow. contains core Golgi elements surrounded by mitochondria associated endoplasmic reticulum. Because their stage specificity perinuclear rather than spherical distribution, these...
In Drosophila oocytes, precise localization of the posterior determinant, Oskar, is required for patterning. This precision accomplished by a localization-dependent translational control mechanism that ensures translation only correctly localized oskar transcripts. Although progress has been made in identifying factors and repressors oskar, none known components complex both processes. Here, we report identification Cup as novel component RNP complex. cup mRNA necessary to recruit plus...
Localization of bicoid (bcd) mRNA to the anterior and oskar (osk) posterior Drosophila oocyte is critical for embryonic patterning. Previous genetic studies implicated exuperantia (exu) in bcd localization, but its role this process not understood. We have biochemically isolated Exu show that it part a large RNase-sensitive complex contains at least seven other proteins. One these proteins was identified as cold shock domain RNA-binding protein Ypsilon Schachtel (Yps), which we binds...
Germ cells serve as intriguing examples of differentiated that retain the capacity to generate all cell types an organism. Here we used functional genomic approaches in planarians identify genes required for proper germ development. We conducted microarray analyses and situ hybridization discover validate cell-enriched transcripts, then RNAi screen discrete stages The majority identified encode conserved RNA-binding proteins, several which have not been implicated previously also show a...
The ability of enzymes to assemble into visible supramolecular complexes is a widespread phenomenon. Such have been hypothesized play number roles; however, little known about how the regulation enzyme activity coupled assembly/disassembly these cellular structures. CTP synthase an ideal model system for addressing this question because its regulated via multiple mechanisms and filament-forming evolutionarily conserved. Our structure-function studies in Saccharomyces cerevisiae reveal that...
Despite the proliferation of proteins that can form filaments or phase-separated condensates, it remains unclear how this behavior is distributed over biological networks. We have found 60 440 yeast metabolic enzymes robustly structures, including 10 assemble within mitochondria. Additionally, ability to enriched at branch points on several pathways. The assembly first point in de novo purine biosynthesis coordinated, hierarchical, and based their position pathway, while second are recruited...
It has become more evident that long-term cigarette smoking (LTCS) an important extrapulmonary toxicity. The aim of the study was to investigate time-dependent effects smoke exposure on exercise capacity, markers systemic inflammation, and skeletal muscle structure. c57bl/6j-mice were either exposed mainstream for 6 h/day, 5 days/wk [smoke-exposed (SE) group] or assigned control, unexposed group (Con group). SE mice 8, 16, 24, 32 wk Con used as age-matched controls. Exercise capacity...
Nogo receptor (NgR)-mediated control of axon growth relies on the central nervous system-specific type I transmembrane protein Lingo-1. Interactions between Lingo-1 and NgR, along with a complementary co-receptor, result in neurite axonal collapse. In addition, inhibitory role is particularly important regulation oligodendrocyte differentiation myelination, suggesting that pharmacological modulation function could be novel approach for nerve repair remyelination therapies. Here we report...
Drosophila Kinesin-73 (Khc-73), which plays a role in mitotic spindle polarity neuroblasts, is metazoan-specific member of the Kinesin-3 family motors, includes mammalian KIF1A and Caenorhabditis elegans Unc-104. The mechanism motors has been controversial because some studies have reported that they transport cargo as monomers whereas other suggested dimer mechanism. Here, we performed single-molecule motility cell biological Khc-73. We find constructs containing motor conserved short...
Subcellular localization of mRNAs within the Drosophila oocyte is an essential step in body patterning. Yps, a Y-box protein, component ovarian ribonucleoprotein complex that also contains Exu, protein plays role mRNA localization. proteins are known translational regulators, suggesting this might regulate translation as well Here we examine yps gene these events. We show interacts genetically with orb, positive regulator oskar and translation. The nature genetic interaction indicates acts...
Structure-based approaches for drug design generally do not incorporate solvent effects and dynamic information to predict inhibitor-binding affinity because of practical limitations. The matrix metalloproteinases (MMPs) have previously been demonstrated exhibit significant mobility in their active sites. This characteristic significantly complicates the process based on static structures, which was clearly observed a class hydroxamic acids containing butynyl moiety. Compound 1 expected be...
Stress granules (SGs) are evolutionarily conserved condensates of ribonucleoproteins that assemble in response to metabolic stresses. Because aberrant SG formation is associated with amyotrophic lateral sclerosis (ALS), understanding the connection between activity and composition can provide therapeutic insights into neurodegeneration. Here, we identify 17 enzymes recruited yeast SGs physiological growth stress. Furthermore, product one these enzymes, AdoMet, a regulator assembly...
Vg1, a member of the transforming growth factor-beta family involved in mesoderm induction, is translated subsequent to localization its mRNA vegetal pole Xenopus oocytes. Whereas Vg1 known be directed by 3' untranslated region (UTR), basis translational regulation unknown. We show here that UTR causes repression two different reporter mRNAs A 350-nucleotide UTR, which distinct from element, necessary and sufficient for mediating specifically binds 38-kDa polypeptide. The activity found...
Abstract Recent work has found that many metabolic enzymes have the ability to polymerize in response changes or environmental stress. This is well conserved for few enzyme paralogs been studied yeast. Here we describe first set of paralogs, Asn1p and Asn2p, differential assembly behavior. Asn2p both co-assemble into filaments nutrient limitation. However, form strictly dependent on presence Asn1p. Using mutations block activity but effects polymerization, polymers are unlikely acquired a...
The self-assembly of metabolic enzymes into filaments or foci highlights an intriguing mechanism for the regulation activity. Recently, we identified conserved polymerization phosphoribosyl pyrophosphate synthetase (PRPS), which catalyzes first step in purine nucleotide synthesis, yeast and cultured mammalian cells. While previous work has revealed that loss PRPS activity regulates retinal development zebrafish, extent to filament formation affects tissue remains unknown.By generating novel...