A5067509815- Mosquito-borne diseases and control
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- Viral Infections and Vectors
- Insect symbiosis and bacterial influences
- Lipid Membrane Structure and Behavior
- Melanoma and MAPK Pathways
- RNA Research and Splicing
- Malaria Research and Control
- Protein Kinase Regulation and GTPase Signaling
- HIV Research and Treatment
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Receptor Mechanisms and Signaling
- Bacteriophages and microbial interactions
- Machine Learning in Bioinformatics
- Influenza Virus Research Studies
- Antimicrobial Peptides and Activities
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- ATP Synthase and ATPases Research
- Atmospheric chemistry and aerosols
- Galectins and Cancer Biology
Agency for Science, Technology and Research
2016-2025
Bioinformatics Institute
2015-2024
Novartis (Switzerland)
2023
A*STAR Graduate Academy
2022
University of Tartu
2021
Genome Institute of Singapore
2021
Duke-NUS Medical School
2021
Foundation for Biomedical Research
2021
Universität Innsbruck
2012-2019
Korea Institute for Advanced Study
2019
Abstract. Cloud glaciation is critically important for the global radiation budget (albedo) and initiation of precipitation. But freezing pure water droplets requires cooling to temperatures as low 235 K. Freezing at higher presence an ice nucleator, which serves a template arranging molecules in ice-like manner. It often assumed that these nucleators have be insoluble particles. We point out also free macromolecules are dissolved can efficiently induce nucleation: size such nucleating...
Microscopic viscosity (microviscosity) is a key determinant of diffusion in the cell and defines rate biological processes occurring at nanoscale, including enzyme-driven metabolism protein folding. Here we establish rotor-based organelle imaging (ROVI) methodology that enables real-time quantitative mapping microviscosity. This approach uses environment-sensitive dyes termed molecular rotors, covalently linked to genetically encoded probes provide compartment-specific microviscosity...
In this study we investigate π-stacking interactions of a variety aromatic heterocycles with benzene using dispersion corrected density functional theory. We calculate extensive potential energy surfaces for parallel-displaced interaction geometries. find that contributes significantly to the and is complemented by varying degree electrostatic interactions. identify geometric preferences minimum energies set 13 5- 6-membered frequently encountered in small drug-like molecules. demonstrate...
Abstract Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure interaction mapping on four DENV ZIKV strains inside virions in infected cells. Comparative analysis SHAPE reactivities across serotypes nominates potentially functional regions highly structured, conserved, contain low synonymous mutation rates. Interaction by SPLASH identifies many...
SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) mutant (Δ382) in cells using Illumina Nanopore platforms. We identify twelve potentially functional structural elements within genome, observe that subgenomic RNAs can form different structures, WT Δ382 virus genomes fold differently. Proximity ligation sequencing hundreds genome between host RNAs. binds strongly mitochondrial small nucleolar extensively...
Bacterial microcompartments (BMCs) are nanoscale proteinaceous organelles that encapsulate enzymes from the cytoplasm using an icosahedral protein shell resembles viral capsids. Of particular interest carboxysomes (CBs), which sequester CO2-fixing ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) to enhance carbon assimilation. The carboxysome serves as a semi-permeable barrier for passage of metabolites in and out CO2 fixation. How directs influx efflux molecules effective manner...
Abstract RNA structure is critical for multiple steps in gene regulation. However, how the structures of transcripts differ both within and between individual cells unknown. Here we develop a SHAPE-inspired method called single-cell probing that enables simultaneous determination transcript secondary abundance at resolution. We apply to human embryonic stem differentiating neurons. Remarkably, more homogeneous compared with neurons, greatest homogeneity found coding regions. More extensive...
Zika virus (ZIKV) infections have been linked with neurological complications and congenital syndrome. Given the high level of homology between ZIKV related flavivirus dengue (DENV), we investigated cross-reactivity using a panel DENV human mAbs. A majority mAbs showed binding to virions, several exhibiting neutralizing capacities against in vitro. Three best ZIKV-neutralizing were found recognize diverse epitopes on envelope (E) glycoprotein: highly conserved fusion-loop peptide,...
To analyse the proportions of protein identity between Zika virus and dengue, Japanese encephalitis, yellow fever, West Nile chikungunya viruses as well polymorphism different strains.We used published sequences for obtained other from National Center Biotechnology Information (NCBI) database or NCBI variation resource. We BLASTP to find regions viruses. quantified each viruses, within-Zika all amino acid k-mers across proteome, with k ranging 6 100. assessed accessibility fragments by...
Cyanobacteria are intricately organized, incorporating an array of internal thylakoid membranes, the site photosynthesis, into cells no larger than other bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in substantial production hydrocarbons environment. All sequenced cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting important, undefined physiological role for these compounds. Here, we demonstrate that hydrocarbon-deficient mutants Synechococcus sp....
Ribonucleic acid (RNA) plays a variety of crucial roles in fundamental biological processes. Recently, RNA has become an interesting drug target, emphasizing the need to improve our understanding its structures and functions. Over years, sequencing technologies have produced enormous amount unlabeled data, which hides important knowledge potential. Motivated by successes protein language models, we introduce RiboNucleic Acid Language Model (RiNALMo) help unveil hidden code RNA. RiNALMo is...
Significance The work summarized in this paper is based on the simple but unexpected observation that addition of lipopolysaccharide (LPS) or bacteria to human wound fluids leads precipitation protein aggregates, a phenomenon not observed plasma. Using broad mix technologies ranging from biophysical, biochemical, and microbiological methods fluorescence electron microscopy, silico modeling studies materials, we demonstrate here previously undisclosed role C-terminal thrombin fragments about...
Dengue virus (DENV) infection affects millions of people and is becoming a major global disease for which there no specific available treatment. pep14-23 recently designed peptide, based on conserved segment DENV capsid (C) protein. It inhibits the interaction C with host intracellular lipid droplets (LDs), crucial viral replication. Combining bioinformatics biophysics, here, we analyzed structure ability to bind different phospholipids, relating that information full-length C. We show...
Zika virus (ZIKV) is an ongoing global public health emergency with 70 countries and territories reporting evidence of ZIKV transmission since 2015. On 27 August 2016, Singapore reported its first case local identified cluster. Here, we report the genome sequences strains from two cases find through phylogenetic analysis that these form earlier branch distinct recent large outbreak in Americas.
Circular RNAs are an increasingly important class of RNA molecules that can be engineered as vaccines and therapeutics. Here, we screened eight different group I introns for their ability to circularize delineated features function. First, identified the Scytalidium dimidiatum intron causing minimal innate immune activation inside cells, underscoring its potential serve effective vaccine without triggering unwanted reactogenicity. Additionally, mechanistic structure analysis was used...
A purely information theory-guided approach to quantitatively characterize protease specificity is established. We calculate an entropy value for each subpocket based on sequences of cleaved substrates extracted from the MEROPS database. compare our results with known profiles individual proteases and groups (e.g. serine proteases, metallo proteases) reflect them quantitatively. Summation subpocket-wise cleavage contributions yields a measure overall substrate specificity. This total allows...
Activated G protein-coupled receptors (GPCRs) and receptor tyrosine kinases relay extracellular signals through spatial temporal controlled kinase GTPase entities. These enzymes are coordinated by multifunctional scaffolding proteins for precise intracellular signal processing. The cAMP-dependent protein A (PKA) is the prime example compartmentalized transmission downstream of distinct GPCRs. A-kinase anchoring tether PKA to specific sites ensure precision directionality phosphorylation...
Oncogenic BRAF mutations initiate tumor formation by unleashing the autoinhibited kinase conformation and promoting RAS-decoupled proliferative RAF-MEK-ERK signaling. We have engineered luciferase-based biosensors to systematically track full-length conformations interactions affected tumorigenic GTP loading of RAS. Binding structurally diverse αC-helix-OUT inhibitors (BRAFi) showed differences in specificity efficacy shifting patient mutation-containing reporters from definitive opened more...
Glycans play a vital role in large number of cellular processes. Their complex and flexible nature hampers structure–function studies using experimental techniques. Molecular dynamics (MD) simulations can help understanding dynamic aspects glycans if the force field parameters used reproduce key experimentally observed properties. Here, we present optimized coarse-grained (CG) Martini for N-glycans, calibrated against derived binding affinities lectins. The CG bonded were obtained from...
Thrombin-derived C-terminal peptides (TCPs), including a major 11-kDa fragment (TCP96), are produced through cleavage by human neutrophil elastase and aggregate lipopolysaccharide (LPS) the Gram-negative bacterium Escherichia coli. However, physiological roles of TCP96 in controlling bacterial infections reducing LPS-induced inflammation unclear. Here, using various biophysical methods, silico molecular modeling, microbiological cellular assays, animal models, we examined structural features...