A5019252510- Fungal and yeast genetics research
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Gut microbiota and health
- RNA modifications and cancer
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- RNA and protein synthesis mechanisms
- Dermatology and Skin Diseases
- Bacterial Identification and Susceptibility Testing
- Food Allergy and Anaphylaxis Research
- Mycobacterium research and diagnosis
- Allergic Rhinitis and Sensitization
- Genomics and Phylogenetic Studies
- Asthma and respiratory diseases
- Hippo pathway signaling and YAP/TAZ
- Cancer-related molecular mechanisms research
- Barrier Structure and Function Studies
- Probiotics and Fermented Foods
- Photosynthetic Processes and Mechanisms
- Plant Genetic and Mutation Studies
- Plant and Fungal Interactions Research
- Microtubule and mitosis dynamics
- Plant Disease Resistance and Genetics
- Cellular Mechanics and Interactions
Genome Institute of Singapore
2021-2024
Agency for Science, Technology and Research
2022-2024
National University of Singapore
2023
The Francis Crick Institute
2016-2022
Nanyang Technological University
2022
University College London
2015
Intercellular junctions are crucial for mechanotransduction, but whether tight contribute to the regulation of cell–cell tension and adherens is unknown. Here, we demonstrate that junction protein ZO-1 regulates acting on VE-cadherin–based junctions, cell migration, barrier formation primary endothelial cells, as well angiogenesis in vitro vivo. depletion led disruption, redistribution active myosin II from stress fibers, reduced VE-cadherin loss junctional mechanotransducers such vinculin...
Abstract Human blood is conventionally considered sterile but recent studies suggest the presence of a microbiome in healthy individuals. Here we characterized DNA signatures microbes 9,770 individuals using sequencing data from multiple cohorts. After filtering for contaminants, identified 117 microbial species blood, some which had replication. They were primarily commensals associated with gut ( n = 40), mouth 32) and genitourinary tract 18), distinct pathogens detected hospital cultures....
Differentiation programs such as meiosis depend on extensive gene regulation to mediate cellular morphogenesis. Meiosis requires transient removal of the outer kinetochore, complex that connects microtubules chromosomes. How meiotic expression program temporally restricts kinetochore function is unknown. We discovered in budding yeast, inactivation occurs by reducing abundance a limiting subunit, Ndc80. Furthermore, we uncovered an integrated mechanism acts at transcriptional and...
Abstract Despite extensive efforts to address it, the vastness of uncharacterized ‘dark matter’ microbial genetic diversity can impact short-read sequencing based metagenomic studies. Population-specific biases in genomic reference databases further compound this problem. Leveraging advances hybrid assembly (using short and long reads) Hi-C technologies a cross-sectional survey, we deeply characterized 109 gut microbiomes from three ethnicities Singapore comprehensively reconstruct 4497...
The skin microbiome is an extensive community of bacteria, fungi, mites, viruses and archaea colonizing the skin. Fluctuations in composition have been observed atopic dermatitis (AD) food allergy (FA), particularly early life, established disease, associated with therapeutics. However, AD a multifactorial disease characterized by barrier aberrations modulated genetics, immunology, environmental influences, thus not sole feature this disease. Future research should focus on mechanistic...
Cell differentiation programs require dynamic regulation of gene expression. During meiotic prophase in Saccharomyces cerevisiae, expression the kinetochore complex subunit Ndc80 is downregulated by a 5’ extended long undecoded NDC80 transcript isoform. Here we demonstrate transcriptional interference mechanism that responsible for inhibiting coding mRNA Transcription from distal promoter directs Set1-dependent histone H3K4 dimethylation and Set2-dependent H3K36 trimethylation to establish...
Abstract Background The start and end sites of messenger RNAs (TSSs TESs) are highly regulated, often in a cell-type-specific manner. Yet the contribution transcript diversity regulating gene expression remains largely elusive. We perform an integrative analysis multiple synchronized cell-fate transitions quantitative genomic techniques Saccharomyces cerevisiae to identify regulatory functions associated with transcribing alternative isoforms. Results Cell-fate feature widespread elevated...
Highlights•Expression of divergent noncoding RNAs is repressed by Rap1•Rap1 prevents initiation transcription near its binding sites•Rap1 provides directionality toward productive transcriptionSummaryMany active eukaryotic gene promoters exhibit transcription, but the mechanisms restricting expression these transcripts are not well understood. Here, we demonstrate how a sequence-specific factor represses at highly expressed genes in yeast. We find that depletion Rap1 induces large fraction...
Abstract Yeast cells enter and undergo gametogenesis relatively asynchronously, making it technically challenging to perform stage-specific genomic biochemical analyses. Cell-to-cell variation in the expression of master regulator entry into sporulation, IME1, has been implicated be underlying cause asynchronous sporulation. Here, we find that timing IME1 is critical importance for inducing sporulation synchronously. When force from an inducible promoter incubated medium 2 hr, vast majority...
Long undecoded transcript isoforms (LUTIs) represent a class of non-canonical mRNAs that downregulate gene expression through the combined act transcriptional and translational repression. While single studies revealed important aspects LUTI-based repression, how these features affect regulation on global scale is unknown. Using leader direct RNA sequencing, here, we identify 74 LUTI candidates are specifically induced in meiotic prophase. Translational repression appears to be ubiquitous...
Transcription through noncoding regions of the genome is pervasive. How these transcription events regulate gene expression remains poorly understood. Here, we report that, in S. cerevisiae, levels a region, IRT2, located upstream promoter inducer meiosis, IME1, opposing chromatin and states. At low levels, act IRT2 promotes histone exchange, delivering acetylated H3 lysine 56 to locally. The subsequent open state directs factor recruitment induces downstream repress IME1 meiotic entry....
Abstract Human blood is conventionally considered sterile. Recent studies have challenged this, suggesting the presence of a microbiome in healthy humans. We present largest investigation to date microbes blood, based on shotgun sequencing libraries from 9,770 subjects. Leveraging availability data multiple cohorts, we stringently filtered for laboratory contaminants identify 117 microbial species detected sampled individuals, some which had signatures DNA replication. These primarily...
The skin microbiome plays an important role in immune homeostasis and health, yet our understanding of vivo microbial gene activity is hindered by the lack a robust, non-invasive protocol for metatranscriptomics across sites. Circumventing challenges low biomass, host contamination, RNA stability, we developed clinically tractable workflow that provides high technical reproducibility profiles (Pearson r>0.95), uniform coverage bodies, strong enrichment mRNAs (2.5-40x;). Applying this to...
LUTIs (Long Undecoded Transcript Isoforms) are 5′-extended and poorly translated mRNAs that can downregulate transcription from promoters more proximal to a gene's coding sequence (CDS). In this protocol, polyA RNA is extracted budding yeast cells undergoing highly synchronized meiosis. Using combination of long-read direct sequencing transcript leader (TL-seq), meiosis-specific systematically identified. Following identification, TL-seq used quantify the abundance both LUTI canonical...
Abstract Human blood is conventionally considered sterile. Recent studies have challenged this, suggesting the presence of a microbiome in healthy humans. We present largest investigation to date microbes blood, based on shotgun sequencing libraries from 9,770 subjects. Leveraging availability data multiple cohorts, we stringently filtered for laboratory contaminants identify 117 microbial species detected sampled individuals, some which had signatures DNA replication. These primarily...
SUMMARY L ong U ndecoded T ranscript Isoforms (LUTIs) represent a class of non-canonical mRNAs that downregulate gene expression through the combined act transcriptional and translational repression. While single studies revealed some important aspects LUTI-based repression, how these features impact regulation at global scale is unknown. By using transcript leader direct RNA sequencing, here we identify 74 LUTI candidates are expressed specifically during meiotic prophase. Translational...
ABSTRACT Many long noncoding RNAs (lncRNAs) act in cis through transcription-coupled chromatin alterations that drive changes local gene expression. How some -acting lncRNAs promote and others repress expression remains poorly understood. Here we report S. cerevisiae transcription levels of the lncRNA IRT2 , located upstream promoter inducer meiosis gene, regulate opposing states. Low displays enhancer RNA-like features. At these levels, promotes histone exchange delivering acetylated H3...
Abstract Despite extensive efforts to address it, the vastness of uncharacterized ‘dark matter’ microbial genetic diversity can impact short-read sequencing based metagenomic studies. Population-specific biases in genomic reference databases further compound this problem. Leveraging advances long-read and Hi-C technologies, we deeply characterized 109 gut microbiomes from three ethnicities Singapore comprehensively reconstruct 4,497 medium high-quality metagenome assembled genomes, 1,708...
An amendment to this paper has been published and can be accessed via the original article.
The skin microbiome is an extensive community of bacteria, fungi, mites, and viruses colonizing the skin. Fluctuations in composition have been observed atopic dermatitis (AD) food allergy (FA), particularly early life, established disease, associated with therapeutics. However, AD a multifactorial disease characterized by barrier aberrations modulated genetics, immunology, environmental influences, thus not sole feature this disease. Future research should focus on mechanistic understanding...