Biology subjects

Hong, S.-C.

Publications and source records attributed to Hong, S.-C..

7 recordsLinked to original sources

bioRxiv2025

Nanoscopy of Organelle Handoff Portals Reveals Direct Coupling between ER Remodeling and Microtubule-Based Transport

How biosynthetic organelles leave the endoplasmic reticulum (ER) and engage with microtubule tracks remains a central question. Combining interferometric scattering with fluorescence nanoscopy, we tracked nanometer-scale handoff events in living cells. ER-derived organelles undergo biased diffusion along ER tubules toward nearby microtubules. ER three-way junctions function as nanoscopic hubs where cargo pauses, contacts multiple microtubules, and then launches onto a track for long-range travel. Remarkably, the ER maintains a membrane tether to the departing cargo, extending its tubules and forming new junctions, thereby coupling inter-network transfer with membrane morphogenesis. These observations reveal an integrated mechanism that links organelle biogenesis, directional trafficking, and continual ER- and cellular remodeling, underscoring the ERs active role in steering transport and repurposing its own output within the crowded intracellular environment.

cell biology↗

bioRxiv2024

Determination of the absolute concentration of Rayleigh particles via scattering microscopy

Nanoparticles are crucial in diverse fields such as healthcare, electronics, and energy. Their small size allows them to cross biological barriers, enhancing drug delivery but also posing health risks. Accurate characterization of nanoparticles is essential for assessing their safety and efficacy, particularly in medical applications. Traditional methods such as dynamic light scattering and mass spectrometry have limitations in sensitivity and range of application. To address these challenges, we introduce the interferometric Concentration Analyzer and Ultrasmall Nanoparticle Tracker (iCAUNT), a technique for detecting and quantifying nanoparticles smaller than one-tenth of the imaging light wavelength. As a non-invasive method, iCAUNT provides precise size and concentration measurements of biological and synthetic nanoparticles, offering significant potential for diagnostics, therapeutics, and broader nanoscience applications.

biophysics↗

bioRxiv2022

Two opposing effects of monovalent cations on the stability of i-motif structure

At acidic pH, cytosine-rich single-stranded DNA can be folded into a tetraplex structure called i-motif (iM). In recent studies, the effect of monovalent cations on the stability of iM structures has been addressed, but a consensus about the issue has not been reached yet. Thus, we investigated the effects of various factors on the stability of iM structures using fluorescence resonance energy transfer (FRET)-based analysis for three types of iM derived from human telomere sequences. We confirmed that the iM structure is destabilized as the concentration of monovalent cations (Li+, Na+, K+) increases and that Li+ has the greatest tendency of destabilization. This cation-induced destabilization is rather unexpected and specific to the iM structure, considering the cations electrostatic effect of supporting DNA folding. Monovalent cations of different kinds promote the flexibility of single-stranded DNA (ssDNA) and the stability of folded DNA structures to different degrees, suggesting that the size of cation be a key factor in its function. All taken together, we conclude that the stability of iM structures is controlled by the subtle balance of the two counteractive effects of monovalent cations, electrostatic screening and disruption of cytosine base pairing.

biophysics↗

bioRxiv2022

Long-term cellular cargo tracking reveals intricate trafficking through active cytoskeletal networks

A eukaryotic cell is a microscopic world within which efficient material transport is essential. To examine cargo transport in a crowded cellular environment, we tracked unlabeled cargos in directional motion in a massively parallel fashion using the interferometric scattering microscopy. Our label-free, cargo-tracing method revealed not only dynamic cargo transportation but also the fine architecture of the actively used cytoskeletal highways and the long-term evolution of the associated traffic at sub-diffraction resolution via a myriad of molecular strokes. Cargos experience a traffic jam, but they have an effective strategy to circumvent it: moving together in tandem or migrating collectively. All taken together, a cell is an incredibly complex and busy space where the principle and practice in transportation intriguingly parallel those of our macroscopic world.

biophysics↗

bioRxiv2018

Narcolepsy risk loci are enriched in immune cells and suggest autoimmune modulation of the T cell receptor repertoire

Type 1 narcolepsy (T1N) is a neurological condition, in which the death of hypocretin-producing neurons in the lateral hypothalamus leads to excessive daytime sleepiness and symptoms of abnormal Rapid Eye Movement (REM) sleep. Known triggers for narcolepsy are influenza-A infection and associated immunization during the 2009 H1N1 influenza pandemic. Here, we genotyped all remaining consented narcolepsy cases worldwide and assembled this with the existing genotyped individuals. We used this multi-ethnic sample in genome wide association study (GWAS) to dissect disease mechanisms and interactions with environmental triggers (5,339 cases and 20,518 controls). Overall, we found significant associations with HLA (2 GWA significant subloci) and 11 other loci. Six of these other loci have been previously reported (TRA, TRB, CTSH, IFNAR1, ZNF365 and P2RY11) and five are new (PRF1, CD207, SIRPG, IL27 and ZFAND2A). Strikingly, in vaccination-related cases GWA significant effects were found in HLA, TRA, and in a novel variant near SIRPB1. Furthermore, IFNAR1 associated polymorphisms regulated dendritic cell response to influenza-A infection in vitro (p-value =1.92*10-25). A partitioned heritability analysis indicated specific enrichment of functional elements active in cytotoxic and helper T cells. Furthermore, functional analysis showed the genetic variants in TRA and TRB loci act as remarkable strong chain usage QTLs for TRAJ*24 (p-value = 0.0017), TRAJ*28 (p-value = 1.36*10-10) and TRBV*4-2 (p-value = 3.71*10-117). This was further validated in TCR sequencing of 60 narcolepsy cases and 60 DQB1*06:02 positive controls, where chain usage effects were further accentuated. Together these findings show that the autoimmune component in narcolepsy is defined by antigen presentation, mediated through specific T cell receptor chains, and modulated by influenza-A as a critical trigger.

genetics↗

bioRxiv2018

Climate Change Influences the Japanese Cedar (Cryptomeria japonica) Pollen Count and Sensitization Rate in South Korea

BackgroundJapanese cedar pollen (JCP) is the major outdoor allergen for spring pollinosis and seasonal allergic rhinitis (SAR) caused by JCP is the most common disease in Jeju Island, South Korea and in Japan. Prior to our research, JCP counts were strongly temperature dependent and were significantly associated with the JCP sensitization rate and JC pollinosis. This event may still be ongoing due to the effects of global climate change, such as increasing temperature.\n\nMethods and FindingFor these reasons, we are studying the correlation among increasing temperatures, the JCP counts in the atmosphere and the JCP sensitization rate.\n\nConclusionsIn this study, our data show that increasing temperatures in January and April might lead to earlier and longer JCP seasons and that earlier and longer JCP seasons lead to an increase in the JCP sensitization rate, which influences the prevalence of JC pollinosis.

epidemiology↗

bioRxiv2016

Decoding Single Molecule Time Traces with Dynamic Disorder

Single molecule time trajectories of biomolecules provide glimpses into complex folding landscapes that are difficult to visualize using conventional ensemble measurements. Recent experiments and theoretical analyses have highlighted dynamic disorder in certain classes of biomolecules, whose dynamic pattern of conformational transitions is affected by slower transition dynamics of internal state hidden in a low dimensional projection. A systematic means to analyze such data is, however, currently not well developed. Here we report a new algorithm - Variational Bayes-double chain Markov model (VB-DCMM) - to analyze single molecule time trajectories that display dynamic disorder. The proposed analysis employing VB-DCMM allows us to detect the presence of dynamic disorder, if any, in each trajectory, identify the number of internal states, and estimate transition rates between the internal states as well as the rates of conformational transition within each internal state. Applying VB-DCMM algorithm to single molecule FRET data of H-DNA in 100 mM-Na+ solution, followed by data clustering, we show that at least 6 kinetic paths linking 4 distinct internal states are required to correctly interpret the duplex-triplex transitions of H-DNA.\n\nAuthor SummaryWe have developed a new algorithm to better decode single molecule data with dynamic disorder. Our new algorithm, which represents a substantial improvement over other methodologies, can detect the presence of dynamic disorder in each trajectory and quantify the kinetic characteristics of underlying energy landscape. As a model system, we applied our algorithm to the single molecule FRET time traces of H-DNA. While duplex-triplex transitions of H-DNA are conventionally interpreted in terms of two-state kinetics, slowly varying dynamic patterns corresponding to hidden internal states can also be identified from the individual time traces. Our algorithm reveals that at least 4 distinct internal states are required to correctly interpret the data.

biophysics↗