A5045594074- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Neurogenetic and Muscular Disorders Research
- Cytomegalovirus and herpesvirus research
- Toxoplasma gondii Research Studies
- Chromatin Remodeling and Cancer
- Immune Cell Function and Interaction
- Advanced biosensing and bioanalysis techniques
- Botanical Research and Chemistry
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Bacteriophages and microbial interactions
- Biochemical and Structural Characterization
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Apelin-related biomedical research
- Genomics and Chromatin Dynamics
- Cancer Immunotherapy and Biomarkers
- Nuclear Receptors and Signaling
- Bacterial Genetics and Biotechnology
- Immunotherapy and Immune Responses
- Streptococcal Infections and Treatments
National University of Singapore
2020-2021
National University Cancer Institute, Singapore
2020-2021
Fred Hutch Cancer Center
2017-2020
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2019
Cancer Research Center
2019
University of Washington
2019
Harvard University
2013-2018
Whitehead Institute for Biomedical Research
2009
Maxim Integrated (United Kingdom)
2009
It has been assumed that most, if not all, signals regulating early development have identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence overproduction of Toddler reduce the movement mesendodermal cells gastrulation. Local ubiquitous production promote cell movement, suggesting is neither an attractant nor repellent but acts globally as...
Large-scale genomics and computational approaches have identified thousands of putative long non-coding RNAs (lncRNAs). It has been controversial, however, as to what fraction these is truly non-coding. Here, we combine ribosome profiling with a machine-learning approach validate lncRNAs during zebrafish development in high throughput manner. We find that dozens proposed are protein-coding contaminants many profiles resemble the 5' leaders coding RNAs. Analysis data from embryonic stem cells...
Abstract Upstream open reading frames (uORFs) are ubiquitous repressive genetic elements in vertebrate mRNAs. While much is known about the regulation of individual genes by their uORFs, range uORF-mediated translational repression genomes largely unexplored. Moreover, it unclear whether effects uORFs conserved across species. To address these questions, we analyse transcript sequences and ribosome profiling data from human, mouse zebrafish. We find that depleted near coding (CDSes) have...
The unique reactivity of two sortase enzymes, SrtAstaph from Staphylococcus aureus and SrtAstrep Streptococcus pyogenes, is exploited for site-specific labeling a single polypeptide with different labels at its N C termini. used to label the protein's terminus an LPXTG site fluorescently labeled dialanine nucleophile. Selective N-terminal proteins containing glycine residues achieved using LPXT derivatives. generality demonstrated by near-quantitative multiple protein substrates excellent...
Abstract Background All types of facioscapulohumeral muscular dystrophy (FSHD) are caused by the aberrant activation somatically silent DUX4 gene, expression which initiates a cascade cellular events ultimately leading to FSHD pathophysiology. Typically, progressive skeletal muscle weakness becomes noticeable in second or third decade life, yet there many individuals who genetically but develop symptoms much later life remain relatively asymptomatic throughout their lives. Conversely, may...
Short H2A (sH2A) histone variants are primarily expressed in the testes of placental mammals. Their incorporation into chromatin is associated with nucleosome destabilization and modulation alternate splicing. Here, we show that sH2As innately possess features similar to recurrent oncohistone mutations instability. Through analyses existing cancer genomics datasets, find aberrant sH2A upregulation a broad array cancers, which manifest splicing patterns consistent global destabilization. We...
General translational cis-elements are present in the mRNAs of all genes and affect recruitment, assembly, progress preinitiation complexes ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking initiating AUG codon, protein coding sequence length, codon usage. The quantitative contributions these features how why they coordinate to control translation rates not well understood. Here, we show that specify...
Translation rate per mRNA molecule correlates positively with abundance. As a result, protein levels do not scale linearly levels, but instead the abundance of raised to power an 'amplification exponent'. Here we show that quantitate translational control, translation must be decomposed into two components. One, TRmD, depends on level and defines amplification exponent. The other, TRmIND, is independent amount impacts correlation coefficient between levels. We in Saccharomyces cerevisiae...
The lytic cycle of the protozoan parasite Toxoplasma gondii, which involves a brief sojourn in extracellular space, is characterized by defined transcriptional profiles. For an obligate intracellular that shielded from cytosolic host immune factors parasitophorous vacuole, entry into space likely to exert enormous stress. Due its role cellular stress response, we hypothesize translational control plays important regulating gene expression during cycle. Unlike profiles, insights genome-wide...
Abstract Translation rate per mRNA molecule correlates positively with abundance. As a result, protein levels do not scale linearly levels, but instead the abundance of raised to power an “amplification exponent”. Here we show that quantitate translational control, translation must be decomposed into two components. One, TR mD , depends on level and defines amplification exponent. The other, mIND is independent amount impacts correlation coefficient between levels. We in S. cerevisiae...
Abstract Background All types of facioscapulohumeral muscular dystrophy (FSHD) are caused by the aberrant myogenic activation somatically silent DUX4 gene, which initiates a cascade cellular events ultimately leading to FSHD pathophysiology. Therefore, is dominant gain-of-function disease that amenable modeling overexpression. However, there large variability in patient population. Typically, progressive skeletal muscle weakness becomes noticeable second or third decade life, yet many...
ABSTRACT BACKGROUND General translational cis -elements are present in the mRNAs of all genes and affect recruitment, assembly, progress preinitiation complexes ribosome under many physiological states. These elements are: mRNA folding, upstream open reading frames, specific nucleotides flanking initiating AUG codon, protein coding sequence length, codon usage. The quantitative contributions these features how why they coordinate together to control translation rates not well understood....
Abstract One of the promises precision medicine is to understand and act on inter-individual genetic differences in drug responses. SNPdrug3D contains complete genomic landscape missense single nucleotide variants (SNV) across human proteome at population-wide level that could affect binding. In Singapore SG10K Health global gnomAD cohorts, comprising variations over 80,000 individuals, we identified ~ 1.17 million mapped residues near bound molecules protein-drug complexes relative 6000...