A5002021498- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- Protein Structure and Dynamics
- Protist diversity and phylogeny
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Genetic and Kidney Cyst Diseases
- Enzyme Structure and Function
- Microbial Metabolic Engineering and Bioproduction
- Fetal and Pediatric Neurological Disorders
- Planarian Biology and Electrostimulation
- RNA Research and Splicing
- Photoreceptor and optogenetics research
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Plant and Biological Electrophysiology Studies
- Biomedical Text Mining and Ontologies
- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Cerebrospinal fluid and hydrocephalus
- Magnetic and Electromagnetic Effects
- Protein Degradation and Inhibitors
- Computational Drug Discovery Methods
Cornell University
2019-2024
Institute of Genetics and Cancer
2015-2021
University of Edinburgh
2015-2020
Western General Hospital
2015-2019
Discovery Institute
2005-2013
Howard Hughes Medical Institute
1997
University of California, Berkeley
1996-1997
University of Washington
1997
Lawrence Berkeley National Laboratory
1997
Yale University
1985
Do young and old protein molecules have the same probability to be degraded? We addressed this question using metabolic pulse-chase labeling quantitative mass spectrometry obtain degradation profiles for thousands of proteins. find that >10% proteins are degraded non-exponentially. Specifically, less stable in first few hours their life stabilize with age. Degradation conserved similar two cell types. Many non-exponentially (NED) subunits complexes produced super-stoichiometric amounts...
Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation mammalian protein is critical understanding biological processes, as well disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds human cancer cell lines assign measures functional similarity. From these measures, systematically built...
Aneuploidy, a condition characterized by chromosome gains and losses, causes reduced fitness numerous cellular stresses, including increased protein aggregation. Here, we identify complex stoichiometry imbalances as major cause of aggregation in aneuploid cells. Subunits complexes encoded on excess chromosomes aggregate cells, which is suppressed when expression other subunits coordinately altered. We further show that are either degraded or nearly effective degradation at lowering levels...
The assembly of heteromeric protein complexes is an inherently stochastic process in which multiple genes are expressed separately into proteins, must then somehow find each other within the cell. Here, we considered one ways by prokaryotic organisms have attempted to maximize efficiency complex assembly: organization subunit-encoding operons. Using structure-based predictions, show that operon gene order has been optimized match subunits assemble. Exceptions this almost entirely highly...
There is considerable interest in understanding the effect of transposable elements (TEs) on embryonic development. Studies humans and mice are limited by difficulty working with mammalian embryos relative scarcity active TEs these organisms. The zebrafish an outstanding model for study vertebrate development, over half its genome consists diverse TEs. However, remain poorly characterized. Here we describe demography genomic distribution their expression throughout embryogenesis using bulk...
Cys2-His2 zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by rapid expansion contraction numerous subfamilies across animal phylogeny. The forces mechanisms underlying remain poorly understood, but there growing evidence that, tetrapods, targeting repression lineage-specific transposable elements (TEs) plays a critical role Krüppel-associated box (KZNF) subfamily. Currently, it unknown whether this...
The dorsal–ventral axis in frog embryos is specified during the first cell cycle, when cortex rotates relative to cytoplasmic core along parallel microtubules associated with core. Cytoplasmic transfer experiments suggest that dorsal determinants are transported 90° from vegetal pole equator, even though only 30°. Here we show that, rotation, small endogenous organelles rapidly propelled subcortical toward future side and fluorescent carboxylated beads injected into at least 60° equator. We...
Intraflagellar transport (IFT) is a highly conserved mechanism for motor-driven of cargo within cilia, but how this selectively transported to cilia unclear. WDR35/IFT121 component the IFT-A complex best known its role in ciliary retrograde transport. In absence WDR35, small mutant form fail enrich diverse classes membrane proteins. Wdr35 mouse mutants, non-core components are degraded and core accumulate at base. We reveal deep sequence homology WDR35 other subunits α ß′ COPI coatomer...
Abstract Transposable elements (TEs) make up the bulk of eukaryotic genomes and examples abound TE-derived sequences repurposed for organismal function. The process by which TEs become coopted remains obscure because most cases involve ancient, transpositionally inactive elements. Reports active serving beneficial functions are scarce often contentious due to difficulties in manipulating repetitive sequences. Here we show that recently zebrafish encode products critical embryonic...
ABSTRACT The dorsoventral body axis in amphibian embryos is established by a rotation of the outer cortex relative to inner cytoplasmic core. This cortical depends on microtubules and correlated with parallel array just inside vegetal cortex. Since moves cytoplasm most its are oriented their plus ends facing direction movement, it has been suggested that end-directed motor molecules attached drive moving along array. Using an inverted confocal microscope examine living eggs, however, we...
Abstract Cys2-His2 Zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by rapid expansion contraction numerous subfamilies across animal phylogeny. The forces mechanisms underlying remain poorly understood, but there growing evidence that targeting repression lineage-specific transposable elements (TEs) plays a major role diversification Kruppel-associated box (KZNF) subfamily, which predominates tetrapod...
Abstract There is considerable interest in understanding the effect of transposable elements (TEs) on embryonic development. Studies humans and mice are limited by difficulty working with mammalian embryos, relative scarcity active TEs these organisms. Zebrafish an outstanding model for study vertebrate development over half its genome consists diverse TEs. However, zebrafish remain poorly characterized. Here we describe demography genomic distribution their expression throughout...