A5034754693- RNA Research and Splicing
- RNA modifications and cancer
- Cystic Fibrosis Research Advances
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- Legume Nitrogen Fixing Symbiosis
- TGF-β signaling in diseases
- Glycosylation and Glycoproteins Research
- Genomics and Phylogenetic Studies
- Cancer-related gene regulation
- Amyotrophic Lateral Sclerosis Research
- Neonatal Respiratory Health Research
- Bacterial biofilms and quorum sensing
- Inhalation and Respiratory Drug Delivery
- Genetics and Neurodevelopmental Disorders
- Biochemical and Structural Characterization
- Biofuel production and bioconversion
- Explainable Artificial Intelligence (XAI)
- Crystallization and Solubility Studies
- Oral microbiology and periodontitis research
- Neuroscience and Neural Engineering
- Neurogenetic and Muscular Disorders Research
- Bacteriophages and microbial interactions
- Boron Compounds in Chemistry
- Artificial Intelligence in Healthcare and Education
Singapore Institute of Technology
2025
Campbell University
2023-2024
Hospital for Sick Children
2013-2023
Genus (United Kingdom)
2023
Unifor
2023
Alameda Applied Sciences Corporation (United States)
2023
Texas A&M University
2023
Great Ormond Street Hospital
2022
University College London
2022
SickKids Foundation
2012-2022
Protein phase separation is implicated in formation of membraneless organelles, signaling puncta and the nuclear pore. Multivalent interactions modular binding domains their target motifs can drive separation. However, forces promoting more common intrinsically disordered regions are less understood, with suggested roles for multivalent cation-pi, pi-pi, charge hydrophobic effect. Known phase-separating proteins enriched pi-orbital containing residues thus we analyzed pi-interactions folded...
Optogenetics, which uses visible light to control the cells genetically modified with light-gated ion channels, is a powerful tool for precise deconstruction of neural circuitry neuron-subtype specificity. However, due limited tissue penetration light, invasive craniotomy and intracranial implantation tethered optical fibers are usually required in vivo optogenetic modulation. Here we report mechanoluminescent nanoparticles that can act as local sources brain when triggered by...
The Smad proteins mediate transforming growth factor–β (TGFβ) signaling from the transmembrane serine-threonine receptor kinases to nucleus. anchor for activation (SARA) recruits Smad2 TGFβ receptors phosphorylation. crystal structure of a MH2 domain in complex with Smad-binding (SBD) SARA has been determined at 2.2 angstrom resolution. SBD, an extended conformation comprising rigid coil, α helix, and β strand, interacts sheet three-helix bundle Smad2. Recognition between coil is essential...
We report a discovery that perfunctionalized icosahedral dodecaborate clusters of the type B12(OCH2Ar)12 (Ar = Ph or C6F5) can undergo photo-excitation with visible light, leading to new class metal-free photooxidants. Excitation in these species occurs as result charge transfer between low-lying orbitals located on benzyl substituents and an unoccupied orbital delocalized throughout boron cluster core. Here we show how species, photo-excited benchtop blue LED source, exhibit excited-state...
Understanding the mechanism of action modulator compounds for cystic fibrosis transmembrane conductance regulator (CFTR) is key optimization therapeutics as well obtaining insights into molecular mechanisms CFTR function. We demonstrate direct binding VX-809 to first nucleotide-binding domain (NBD1) human CFTR. Disruption interaction between C-terminal helices and NBD1 core upon observed from chemical shift changes in NMR spectra residues on surface β-strands S3, S9, S10. Binding leads a...
Cytoplasmic mislocalization of FUS-ALS mutants determines aberrant FMRP condensates and protein synthesis repression.
Type IVa pili are bacterial nanomachines required for colonization of surfaces, but little is known about the organization proteins in this system. The Pseudomonas aeruginosa pilMNOPQ operon encodes five key members transenvelope complex facilitating pilus function. While PilQ forms outer membrane secretin pore, functions inner membrane-associated PilM/N/O/P less well defined. Structural characterization a stable C-terminal fragment PilP (PilP(Δ71)) by NMR revealed modified β-sandwich fold,...
Many membraneless organelles are thought to be biomolecular condensates formed by phase separation of proteins and other biopolymers. Post-translational modifications (PTMs) can impact protein behavior, although for many PTMs this aspect their function is unknown. O-linked β-D-N-acetylglucosaminylation (O-GlcNAcylation) an abundant form intracellular glycosylation whose roles in regulating condensate assembly dynamics have not been delineated. Using vitro approach, we found that...
Aims/Purpose: Infants with congenital mobility visual impairment or blindness (MVI/B) walking delays are due to exposure and insufficient contact their environment. Assistive safety devices provide protection. [1 , 2] Our study measured foot motility/gait in pediatric patients a MVI/B quantify the benefits of wearing Pediatric Belt Cane. Methods: Videos fifty (Mean age = 26 mos, SD 10.8) Before After were analyzed using MediaPipe platform perform gait analysis. Subsequent analyses included...
Background: Lung cancer is the leading cause of cancer-related mortality globally, with late-stage diagnoses contributing to poor survival rates. While lung screening low-dose computed tomography (LDCT) has proven effective in reducing among heavy smokers, its limitations, including high false-positive rates and resource intensiveness, restrict widespread use. Liquid biopsy, particularly using microRNA (miRNA) biomarkers, offers a promising adjunct current strategies. This study aimed...
Smad ubiquitination regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that participates in degradation of TGF-β receptors and other targets. Smurf2 WW domains recognize PPXY (PY) motifs on target proteins or adapters, such as Smad7, bind to proteins. We previously demonstrated the isolated WW3 domain Smurf2, but not WW2 domain, can directly a Smad7 PY motif. show here augments this interaction by binding making auxiliary contacts with motif novel E/D-S/T-P motif, which N-terminal all...
Deletion of Phe-508 (F508del) in the first nucleotide binding domain (NBD1) cystic fibrosis transmembrane conductance regulator (CFTR) leads to defects folding and channel gating. NMR data on human F508del NBD1 indicate that an H620Q mutant, shown increase open probability, dual corrector/potentiator CFFT-001 similarly disrupt interactions between β-strands S3, S9, S10 C-terminal helices H8 H9, shifting a preexisting conformational equilibrium from helix coil. appears interact with...
Smurf2 is an E3 ubiquitin ligase that drives degradation of the transforming growth factor-beta receptors and other targets. Recognition by accomplished through intermediary protein, Smad7. Here we have demonstrated WW3 domain can directly bind to Smad7 polyproline-tyrosine (PY) motif. Of particular interest, highly conserved WW binding site Trp, which interacts with target PY motifs, a Phe in domain. To examine this interaction, solution structure complex between motif region...
The most common mutation in cystic fibrosis (CF) patients is deletion of F508 (ΔF508) the first nucleotide binding domain (NBD1) CF transmembrane conductance regulator (CFTR). ΔF508 causes a decrease trafficking CFTR to cell surface and reduces thermal stability isolated NBD1; it well established that both these effects can be rescued by additional revertant mutations NBD1. current paradigm small molecule drug discovery that, like mutations, path may exist correction through chaperone We,...
Abstract Phosphorylation of intrinsically disordered eIF4E binding proteins (4E-BPs) regulates cap-dependent translation by weakening their ability to compete with eIF4G for within the initiation complex. We previously showed that phosphorylation T37 and T46 in 4E-BP2 induces folding a four-stranded beta-fold domain, partially sequestering canonical eIF4E-binding helix. The C-terminal region (C-IDR), remaining after phosphorylation, contains secondary site three other phospho-sites, whose...
Abstract Misofolding of mammalian prion proteins (PrP) is believed to be the cause a group rare and fatal neurodegenerative diseases. Despite intense scrutiny however, mechanism misfolding reaction remains unclear. We perform nuclear Magnetic Resonance thermodynamic stability measurements on C-terminal domains (residues 90–231) two PrP variants exhibiting different pH-induced susceptibilities aggregation: susceptible hamster (GHaPrP) its less rabbit homolog (RaPrP). The pKa histidines in...
Deletion of Phe-508 (F508del) in the first nucleotide-binding domain (NBD1) cystic fibrosis transmembrane conductance regulator (CFTR) results destabilization domain, intramolecular interactions involving and entire channel. The caused by F508del manifests itself defective channel processing gating defects. Here, we present NMR studies effect I539T stabilizing mutation on NBD1 dynamics, with a view to understanding these changes stability. Qualitatively, spectra exhibit significantly more...
Abstract Retinitis pigmentosa and macular degeneration lead to photoreceptor death loss of visual perception. Despite recent progress, restorative technologies for remain largely unavailable. Here, we describe a novel optogenetic prosthesis (FlexLED) based on combination thin-film retinal display activation ganglion cells (RGCs). The FlexLED implant is 30 µm thin, flexible, wireless µLED with 8,192 pixels, each an emission area 66 2 . affixed the surface, electronics package mounted under...
Characterization of the second nucleotide-binding domain (NBD2) cystic fibrosis transmembrane conductance regulator (CFTR) has lagged behind research into NBD1 domain, in part because contains F508del mutation, which is dominant cause fibrosis. Research on NBD2 also been hampered by overall instability and difficulty producing reagents. Nonetheless, multiple disease-causing mutations reside NBD2, critical for CFTR function, channel gating involves NBD1/NBD2 dimerization, catalytically active...
Carborane RAFT agents are introduced as tunable multi-purpose tools acting <sup>1</sup>H NMR spectroscopic handles, Raman probes, and recognition units.