Biology subjects

Jang, S.

Publications and source records attributed to Jang, S..

45 records · Page 3Linked to original sources

bioRxiv2020

Dynamics of replication origin over-activation

We determined replication patterns in cancer cells in which the controls that normally prevent excess replication were disrupted ("re-replicating cells"). Single-fiber analyses suggested that replication origins were activated at a higher frequency in re-replicating cells. However, nascent strand sequencing demonstrated that re-replicating cells utilized the same pool of potential replication origins as normally replicating cells. Surprisingly, re-replicating cells exhibited a skewed initiation frequency correlating with replication timing. These patterns differed from the replication profiles observed in non-re-replicating cells exposed to replication stress, which activated a novel group of dormant origins not typically activated during normal mitotic growth. Hence, disruption of the molecular interactions that regulates origin initiation can activate two distinct pools of potential replication origins: re-replicating cells over-activate flexible origins while replication stress in normal mitotic growth activates dormant origins.

genomics↗

bioRxiv2019

MSL3 coordinates a transcriptional and translational meiotic program in female Drosophila

Gamete formation from germline stem cells (GSCs) is essential for sexual reproduction. However, the regulation of GSC differentiation and meiotic entry are incompletely understood. Set2, which deposits H3K36me3 modifications, is required for differentiation of GSCs during Drosophila oogenesis. We discovered that the H3K36me3 reader Male-specific lethal 3 (MSL3) and the histone acetyltransferase complex Ada2a-containing (ATAC) cooperate with Set2 to regulate entry into meiosis in female Drosophila. MSL3 expression is restricted to the mitotic and early meiotic stages of the female germline, where it promotes transcription of genes encoding synaptonemal complex components and a germline enriched ribosomal protein S19 paralog, RpS19b. RpS19b upregulation is required for translation of Rbfox1, a known meiotic cell cycle entry factor. Thus, MSL3 is a master regulator of meiosis, coordinating the expression of factors required for recombination and GSC differentiation. We find that MSL3 is expressed during mouse spermatogenesis, suggesting a conserved function during meiosis.

developmental biology↗

bioRxiv2019

Measuring three-dimensional dynamics of platelet activation using 3-D quantitative phase imaging

Platelets, or thrombocytes, are anucleated tiny blood cells with an indispensable contribution to the hemostatic properties of whole blood, detecting injured sites at the surface of blood vessels and forming blood clots. Here, we quantitatively and non-invasively investigated the morphological and biochemical alterations of individual platelets during activation in the absence of exogenous agents by employing 3-D quantitative phase imaging (QPI). By reconstructing 3-D refractive index (RI) tomograms of individual platelets, we investigated alterations in platelet activation before and after the administration of various platelet agonists. Our results showed that while the integrity of collagen-stimulated platelets was preserved despite the existence of a few degranulated platelets with developed pseudopods, platelets stimulated by thrombin or thrombin receptor-activating peptide (TRAP) exhibited significantly lower cellular concentration and dry mass than did resting platelets. Our work provides a means to systematically investigate drug-respondents of individual platelets in a label-free and quantitative manner, and open a new avenue to the study of the activation of platelets.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC=\"FIGDIR/small/827436v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (39K):\norg.highwire.dtl.DTLVardef@17fe91eorg.highwire.dtl.DTLVardef@a1b25dorg.highwire.dtl.DTLVardef@1c519d8org.highwire.dtl.DTLVardef@123b6dd_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2019

Global Genetic Cartography of Urban Metagenomes andAnti-Microbial Resistance

We have created a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities across 3 years. This is the first systematic, worldwide study cataloging the urban microbial ecosystem. We identify taxonomically-defined microorganisms collected across three years. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics AMR markers, and novel genetic elements, including 10,928 viral, 1302 bacteria, and 2 archaea novel species. We identify 4,424 species of urban microorganisms and a consistent "core" of 31 species found in nearly all samples that is largely distinct from any human commensal microbiome. Profiles of AMR genes show geographic variation in type and density. Together, these results constitute a high-resolution, global metagenomic atlas, which enables the discovery of new genetic components, highlights potential forensic applications, and provides an essential first draft of the global AMR burden of the worlds cities.

microbiology↗

bioRxiv2019

The Glycolytic Protein Phosphofructokinase Dynamically Relocalizes into Subcellular Compartments with Liquid-like Properties in vivo

While much is known about the biochemical regulation of glycolytic enzymes, less is understood about how they are organized inside cells. Here we built a hybrid microfluidic-hydrogel device for use in Caenorhabditis elegans to systematically examine and quantify the dynamic subcellular localization of the rate-limiting enzyme of glycolysis, phosphofructokinase-1/PFK-1.1. We determine that endogenous PFK-1.1 localizes to distinct, tissue-specific subcellular compartments in vivo. In neurons, PFK-1.1 is diffusely localized in the cytosol, but capable of dynamically forming phase-separated condensates near synapses in response to energy stress from transient hypoxia. Restoring animals to normoxic conditions results in the dispersion of PFK-1.1 in the cytosol, indicating that PFK-1.1 reversibly organizes into biomolecular condensates in response to cues within the cellular environment. PFK-1.1 condensates exhibit liquid-like properties, including spheroid shapes due to surface tension, fluidity due to deformations, and fast internal molecular rearrangements. Prolonged conditions of energy stress during sustained hypoxia alter the biophysical properties of PFK-1.1 in vivo, affecting its viscosity and mobility within phase-separated condensates. PFK-1.1s ability to form tetramers is critical for its capacity to form condensates in vivo, and heterologous self-association domain such as cryptochrome 2 (CRY2) is sufficient to constitutively induce the formation of PFK-1.1 condensates. PFK-1.1 condensates do not correspond to stress granules and might represent novel metabolic subcompartments. Our studies indicate that glycolytic protein PFK-1.1 can dynamically compartmentalize in vivo to specific subcellular compartments in response to acute energy stress via multivalency as phase-separated condensates.

cell biology↗

bioRxiv2019

Modular structure of human olfactory receptor codes reflects the bases of odor perception

The circuits of olfactory signaling are reminiscent of complex computational devices. The olfactory receptor code, which represents the responses of receptors elicited by olfactory stimuli, is effectively an input code for the neural computation of odor sensing. Here, analyzing a recent dataset of the odorant-dependent responses of human olfactory receptors (ORs), we show that the space of human olfactory receptor codes is partitioned into a modular structure where groups of receptors are \"labeled\" for key olfactory features. Our analysis reveals a low-dimensional structure in the space of human odor perception, with the receptor groups as the bases to represent major features in the perceptual odor space. These findings provide a novel evidence that some fundamental olfactory features are already hard-coded at the level of ORs, separately from the higher-level neural circuits.

neuroscience↗

bioRxiv2018

Structural basis of recognition and destabilization of histone H2B ubiquitinated nucleosome by DOT1L histone H3 Lys79 methyltransferase

DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B-ubiquitination. Here, we present cryo-EM structures of DOT1L complex with unmodified and H2B-ubiquitinated nucleosomes, showing that DOT1L recognizes H2B-ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L respectively. Furthermore, the structures combined with single-molecule FRET experiment show that H2B-ubiquitination enhances a non-catalytic function of DOT1L destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.

biophysics↗

bioRxiv2018

Implications for human odor sensing revealed from the statistics of the odorant-receptor interactions

Binding of odorants to olfactory receptors (ORs) elicits downstream chemical and neural signals, which are further processed to odor perception in the brain. Recently, Mainland et al. [Sci. data, (2015) 2:sdata20152] have measured {gtrsim} 500 pairs of odorant-OR interaction by a high-throughput screening assay method, opening a new avenue to understanding the principles of human odor coding. Here, using a recently developed minimal model for OR activation kinetics [J. Phys. Chem. B (2017) 121, 1304-1311], we characterize the statistics of OR activation by odorants in terms of three empirical parameters: the half-maximum effective concentration EC50, the efficacy, and the basal activity. While the data size of odorants is still limited, the statistics offer meaningful information on the breadth and optimality of the tuning of human ORs to odorants, and allow us to relate the three parameters with the microscopic rate constants and binding affinities that define the OR activation kinetics. Despite the stochastic nature of the response expected at individual OR-odorant level, we assess that the confluence of signals in a neuron released from the multitude of ORs is effectively free of noise and deterministic with respect to changes in odorant concentration. Thus, setting a threshold to the fraction of activated OR copy number for neural spiking binarizes the electrophysiological signal of olfactory sensory neuron, thereby making an information theoretic approach a viable tool in studying the principles of odor perception.

systems biology↗

bioRxiv2016

Refractive index tomograms and dynamic membrane fluctuations of red blood cells from patients with diabetes mellitus

In this paper we present the optical characterisations of diabetic red blood cells (RBCs) in a non-invasive manner employing three-dimensional (3-D) quantitative phase imaging. By measuring 3-D refractive index tomograms and 2-D time-series phase images, the morphological (volume, surface area and sphericity), biochemical (haemoglobin concentration and content) and mechanical (membrane fluctuation) parameters were quantitatively retrieved at the individual cell level. With simultaneous measurements of individual cell properties, systematic correlative analyses on retrieved RBC parameters were also performed. Our measurements show that diabetic patients had RBCs of reduced cell sphericity and elevated intracellular haemoglobin concentration and content compared to healthy (non-diabetic) subjects. Furthermore, membrane deformability of diabetic RBCs is significantly lower than that of healthy, non-diabetic RBCs. Interestingly, non-diabetic RBCs exhibit strong correlations between the elevated glycated haemoglobin in RBC cytoplasm and decreased cell deformability, whereas diabetic RBCs do not show correlations. Our observations strongly support the idea that slow and irreversible glycation of haemoglobin and membrane proteins of RBCs by hyperglycaemia significantly compromises RBC deformability in diabetic patients.

biophysics↗