A5000356349- Ion channel regulation and function
- Erythrocyte Function and Pathophysiology
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Neuroscience and Neural Engineering
- Hemoglobinopathies and Related Disorders
- Neuroscience and Neuropharmacology Research
- RNA Interference and Gene Delivery
- Photoreceptor and optogenetics research
- Ion Channels and Receptors
- Cardiac electrophysiology and arrhythmias
- RNA and protein synthesis mechanisms
- Extracellular vesicles in disease
- Connexins and lens biology
- Signaling Pathways in Disease
- MicroRNA in disease regulation
- Neural dynamics and brain function
- Genomics and Chromatin Dynamics
- Mosquito-borne diseases and control
- Force Microscopy Techniques and Applications
- Lipid Membrane Structure and Behavior
- Heat shock proteins research
- RNA Research and Splicing
- Toxin Mechanisms and Immunotoxins
- Biochemical effects in animals
Westlake University
2020-2024
Fudan University
2022-2024
South China Normal University
2019-2021
Abstract The ability to detect low numbers of microbial cells in food and clinical samples is highly valuable but remains a challenge. Here we present detection system (called ‘APC-Cas’) that can very bacterial pathogen without isolation, using three-stage amplification generate powerful fluorescence signals. APC-Cas involves combination nucleic acid-based allosteric probes CRISPR-Cas13a components. It selectively sensitively quantify Salmonella Enteritidis (from 1 10 5 CFU) various types...
MicroRNAs (miRNAs) have been widely investigated as potential biomarkers for early clinical diagnosis of cancer. Developing an miRNA detection platform with high specificity, sensitivity, and exploitability is always necessary. Electrochemiluminescence (ECL) electrogenerated chemiluminescence technology that greatly decreases background noise improves sensitivity. The development a paper-based ECL biosensor further makes suitable point-of-care detection. Recently, clustered regularly...
MicroRNAs (miRNAs) are short noncoding RNAs that post-transcriptionally regulate gene expression. It has been proved the aberrant expression of miRNAs is related to disease and can serve as potential biomarkers for early tumor diagnosis. The clustered regularly interspaced palindromic repeats (CRISPR)/Cas13a a recently discovered CRISPR-RNA (crRNA) guided RNA manipulation tool. recognition target morphologically activate robust nonspecific trans ribonuclease activity Cas13a. This unique...
Abstract Mechanosensitive (MS) ion channels are a ubiquitous type of molecular force sensor sensing forces from the surrounding bilayer. The profound structural diversity in these suggests that mechanisms follow unique blueprints. Here we determine structures plant and mammalian OSCA/TMEM63 proteins, allowing us to identify essential elements for mechanotransduction propose roles putative bound lipids mechanosensation. Briefly, central cavity created by dimer interface couples each subunit...
A cascade CRISPR/cas nucleic acid diagnostic system, which can achieve high-sensitive and single-base specificity without target amplification, was developed for miRNA detection.
Abstract The transmembrane voltage gradient is a general physico-chemical cue that regulates diverse biological function through voltage-gated ion channels. How sensing mediates flows remains unknown at the molecular level. Here, we report six conformations of human Eag2 (hEag2) ranging from closed, pre-open, open, and pore dilation but non-conducting states captured by cryo-electron microscopy (cryo-EM). These multiple illuminate dynamics selectivity filter permeation pathway with delayed...
Channelrhodopsins are popular optogenetic tools in neuroscience, but remain poorly understood mechanistically. Here we report the cryo-EM structures of channelrhodopsin-2 (ChR2) from Chlamydomonas reinhardtii and H. catenoides kalium channelrhodopsin (KCR1). We show that ChR2 recruits an endogenous N-retinylidene-PE-like molecule to a previously unidentified lateral retinal binding pocket, exhibiting reduced light response HEK293 cells. In contrast, (KCR1) binds its canonical pocket under...
OSCA/TMEM63 channels, which have transporter-like architectures, are bona fide mechanosensitive (MS) ion channels that sense high-threshold mechanical forces in eukaryotic cells. The activation mechanism of these is not fully understood. Here we report cryo-EM structures a dimeric pore mutant OSCA1.1-F516A with sequentially extracellular dilated detergent environment. These suggest the sequential dilation resembles flower blooming and couples to contraction each monomer subunit towards dimer...
The constructed Cas13a/crRNA complex is delivered into cytoplasm by PBP <italic>via</italic> endocytosis, followed endosomal escape based on biodegradation of the PBP, and efficiently knocked down Mcl-1 at transcriptional level for breast cancer therapy.
Summary H. catenoides kalium channelrhodopsins ( Hc KCR1 and KCR2) are potassium-selective light-gated ion channels with unique properties for optogenetics. Here we report cryo-electron microscopy (cryo-EM) structures of KCR2 endogenous retinal. Strikingly, one structure HcKCR1 represents the conducting state continuous potassium flow in lumen, while another non-conducting discontinuous flow. Further electrophysiological studies identified extracellular side permeation region as major...
Summary PIEZO channels transmit mechanical force signals to cells, allowing them make critical decisions during development and in pathophysiological conditions. Their fast/slow inactivation modes have been implicated mechanopathologies, but remain poorly understood. Here, we report several near-atomic resolution cryo-EM structures of fast-inactivating wild-type human PIEZO1 (hPIEZO1) its slow-inactivating channelopathy mutants with or without auxiliary subunit MDFIC. Our results suggest...
PIEZO channels transmit mechanical force signals to cells, allowing them make critical decisions during development and in pathophysiological conditions. Their fast/slow inactivation modes have been implicated mechanopathologies, but remain poorly understood. Here, we report several near-atomic resolution cryo-EM structures of fast-inactivating wild-type human PIEZO1 (hPIEZO1) its slow-inactivating channelopathy mutants with or without auxiliary subunit MDFIC. Our results suggest that the...
PIEZO channels transmit mechanical force signals to cells, allowing them make critical decisions during development and in pathophysiological conditions. Their fast/slow inactivation modes have been implicated mechanopathologies, but remain poorly understood. Here, we report several near-atomic resolution cryo-EM structures of fast-inactivating wild-type human PIEZO1 (hPIEZO1) its slow-inactivating channelopathy mutants with or without auxiliary subunit MDFIC. Our results suggest that the...
PIEZO channels transmit mechanical force signals to cells, allowing them make critical decisions during development and in pathophysiological conditions. Their fast/slow inactivation modes have been implicated mechanopathologies, but remain poorly understood. Here, we report several near-atomic resolution cryo-EM structures of fast-inactivating wild-type human PIEZO1 (hPIEZO1) its slow-inactivating channelopathy mutants with or without auxiliary subunit MDFIC. Our results suggest that...
Summary Channelrhodopsins harvest the light and convert photons to cellular ion flow. The selectivity activation mechanism at atomic level remains unknown. Here we describe cryo-EM structures for H. catenoides kalium channelrhodopsin ( Hc KCR1), its paralog, sodium selective CCR), an open state of KCR1 (C110T), voltage-dependent inwardly rectifier (D116N) higher potassium B1 ChR2) from Bilabrum sp , illuminating mechanism. Briefly, hourglass shaped lumen is occupied by stepwise dehydrated in...
Abstract Voltage gradient is a general physical cue that regulates diverse biological function through voltage-gated ion channels. How voltage sensing mediates flows remains unknown at the molecular level. Here, we report six conformations of human Eag2 (hEag2) ranging from closed, pre-open, open, and pore dilation but non-conducting states captured by cryo-electron microscopy (cryo-EM). These multiple illuminate dynamics selectivity filter permeating pathway with delayed rectifier property...
Summary Human Slack (hSlack) channel is abundantly expressed in the central nervous system and regulates numerous physiological processes. Here, we identified hSlack a voltage dependent physical force induced desensitization potassium channel. In cell-attached mode, exhibited large currents without significant delayed rectification or C-type inactivation. After breaking cell membrane resulting inside-out were largely inhibited it transited to strong rectified state. Structural results...