- RNA Research and Splicing
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- 3D Printing in Biomedical Research
- Molecular Junctions and Nanostructures
- Genomics and Chromatin Dynamics
- Gene Regulatory Network Analysis
- Advanced biosensing and bioanalysis techniques
- Microfluidic and Capillary Electrophoresis Applications
- DNA Repair Mechanisms
- Microfluidic and Bio-sensing Technologies
- ATP Synthase and ATPases Research
- Single-cell and spatial transcriptomics
- Force Microscopy Techniques and Applications
- Cell Image Analysis Techniques
- Molecular Biology Techniques and Applications
- Bacterial Genetics and Biotechnology
- Click Chemistry and Applications
- Advanced Multi-Objective Optimization Algorithms
- Lipid metabolism and biosynthesis
- Nanopore and Nanochannel Transport Studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Orbital Angular Momentum in Optics
University of California, Irvine
2021-2025
Shanghai Skin Disease Hospital
2024
Tongji University
2024
Centre National de la Recherche Scientifique
2009-2022
California Institute of Technology
2018-2022
École Normale Supérieure - PSL
2012-2022
Sorbonne Université
2009-2022
Université Paris Cité
2009-2022
Université Paris Sciences et Lettres
2022
Howard Hughes Medical Institute
2020-2022
X chromosome inactivation (XCI) serves as a paradigm for RNA-mediated regulation of gene expression, wherein the long non-coding RNA XIST spreads across in cis to mediate silencing chromosome-wide. In female naive human pluripotent stem cells (hPSCs), is dispersed configuration, and XCI does not occur, raising questions about XIST's function. We found that induces dampening X-linked expression hPSCs. Surprisingly, also targets specific autosomal regions, where it repressive chromatin changes...
Replicative holoenzymes exhibit rapid and processive primer extension DNA synthesis, but inefficient strand displacement synthesis. We investigated the bacteriophage T4 T7 activity on a hairpin substrate manipulated by magnetic trap. Holoenzyme is moderately hindered applied force. In contrast, strongly stimulated force; polymerization favoured at high force, while exonuclease triggered low propose that fork upstream of holoenzyme generates regression pressure which inhibits...
Rapid and processive leading-strand DNA synthesis in the bacteriophage T4 system requires functional coupling between helicase holoenzyme, consisting of polymerase trimeric clamp loaded by loader. We investigated mechanism this on a hairpin substrate manipulated magnetic trap. In stark contrast to isolated enzymes, coupled synthesized at maximum rate without exhibiting fork regression or pauses. unwinding activities were low forces, but became uncoupled displaying separate high forces dNTP...
Non-core spliceosome components are essential, conserved regulators of alternative splicing. They provide concentration-dependent control diverse pre-mRNAs. Many splicing factors direct unproductive their own pre-mRNAs through negative autoregulation. However, the impact such feedback loops on dynamics at single-cell level remains unclear. Here, we developed a system to quantitatively analyze autoregulatory by factor SRSF1 in response perturbations single HEK293 cells. We show that provides...
Abstract The hybridization kinetic of an oligonucleotide to its template is a fundamental step in many biological processes such as replication arrest, CRISPR recognition, DNA sequencing, origami, etc. Although single descriptions exist for special cases this problem, there are no simple general prediction schemes. In work, we have measured experimentally, with fluorescent labelling, the displacement from substrate two situations: one corresponding binding/unbinding on ssDNA and which...
Among chromatin remodeling factors, the ISWI family displays a nucleosome-enhanced ATPase activity coupled to DNA translocation. While these enzymes are known bind DNA, their has not been fully characterized. Here we use TEM imaging and single molecule manipulation investigate interaction between yeast Isw1a. We show that Isw1a highly cooperative ATP-independent binding bridging segments. Under appropriate tension, rare nucleation events can sometimes be observed loop with regular step....
Transcriptomics is one of the largest areas research in biological sciences. Aside from RNA expression levels, significance spatial context has also been unveiled recent decade, playing a critical role diverse processes, subcellular kinetic regulation to cell communication, tissue architecture tumor microenvironment, and more. To systematically unravel positional patterns molecules across subcellular, cellular, transcriptomics techniques have emerged rapidly became an irreplaceable tool set....
The combination of optical tweezers force microscopy and single molecule fluorescence has previously been complicated by trap-induced photobleaching. Recent studies have suggested that this effect is caused a sequential absorption photons, leading to ionization the fluorescent singlet state. In work, we show range effects trapping radiation on common dyes. Using interlaced (IOFF) laser modulation technique, removal simultaneous near infrared dramatically reduces photobleaching effects....
Biological experiments require precise temperature control, necessitating an integrated adjustable system for instruments such as microscopes, microfluidic chambers, or custom incubators. We present a protocol building user-friendly control suitable both in vitro and vivo assays. describe steps preparing materials, assembling the printed circuit board enclosure, fine-tuning heating algorithm accuracy. This can maintain stable of up to 60°C with stabilities under 0.06°C.
Drug-resistant
The RNA exosome plays critical roles in eukaryotic degradation, but it remains unclear how the specifically recognizes its targets. PAXT connection is an adaptor that recruits to polyadenylated RNAs nucleus, especially transcripts at intronic poly(A) sites. Here we show PAXT-mediated degradation induced by combination of a 5' splice site and junction, not either sequence alone. These sequences are bound U1 snRNP cleavage/polyadenylation factors, which turn cooperatively recruit PAXT. As...
Abstract Non-spliceosomal splicing factors are essential, conserved regulators of alternative splicing. They provide concentration-dependent control diverse pre-mRNAs. Many direct unproductive their own pre-mRNAs through negative autoregulation. However, the impact such feedback loops on dynamics at single cell level remains unclear. We developed a system to dynamically, quantitatively analyze autoregulatory by SF2 factor in response perturbations HEK293 cells. Here, we show that provides...
Many imaging techniques for biological systems -- like fixation of cells coupled with fluorescence microscopy provide sharp spatial resolution in reporting locations individuals at a single moment time but also destroy the dynamics they intend to capture. These snapshot observations contain no information about individual trajectories, still encode movement and demographic dynamics, especially when combined well-motivated biophysical model. The relationship between spatially evolving...
Abstract In eukaryotic cells, splicing affects the fate of each pre-mRNA transcript, helping to determine whether it is ultimately processed into an mRNA, or degraded. The efficiency plays a key role in gene expression. However, because depends on levels multiple isoforms at same transcriptional active site (TAS) cell, has been challenging measure. Here, we introduce quantitative single-molecule FISH-based method that enables determination absolute abundances distinct RNA individual TASs....
Abstract Time-lapse microscopy plays critical roles in the studies of cellular dynamics. However, to set up a time-lapse movie experiments is not only laborious but also with low output, mainly due cell-losing problem (i.e., cell moving out limited field view), especially long time recording. To overcome these issues, we have designed cost-efficient way that enables patterning on imaging surfaces without any physical boundaries. Using mouse embryonic stem cells as an example system,...