A5026059874- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- DNA Repair Mechanisms
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- Force Microscopy Techniques and Applications
- Cellular transport and secretion
- Photosynthetic Processes and Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Electron Spin Resonance Studies
- RNA modifications and cancer
- Parkinson's Disease Mechanisms and Treatments
- Telomeres, Telomerase, and Senescence
- Electrospun Nanofibers in Biomedical Applications
- Wnt/β-catenin signaling in development and cancer
- Gold and Silver Nanoparticles Synthesis and Applications
- Complement system in diseases
- Hearing, Cochlea, Tinnitus, Genetics
- Nanocluster Synthesis and Applications
- Advanced Sensor and Energy Harvesting Materials
- ATP Synthase and ATPases Research
University of Illinois Urbana-Champaign
2015-2023
Johns Hopkins University
2019-2023
Howard Hughes Medical Institute
2022-2023
Johns Hopkins Medicine
2022-2023
Pacific Biosciences (United States)
2023
Thermo Fisher Scientific (United States)
2022
Urbana University
2020
Indian Institute of Technology Kanpur
2013-2015
Chhatrapati Shahu Ji Maharaj University
2015
Abstract Single-molecule Förster-resonance energy transfer (smFRET) experiments allow the study of biomolecular structure and dynamics in vitro vivo. We performed an international blind involving 19 laboratories to assess uncertainty FRET for proteins with respect measured efficiency histograms, determination distances, detection quantification structural dynamics. Using two protein systems distinct conformational changes dynamics, we obtained ≤0.06, corresponding interdye distance precision...
The fabrication of tissue engineering scaffolds necessitates amalgamation a multitude attributes including desirable porosity to encourage vascular invasion, desired surface chemistry for controlled deposition calcium phosphate-based mineral as well ability support attachment, proliferation, and differentiation lineage specific progenitor cells. Scaffold often includes additional treatments bring about changes in the chemistry. In this perspective, review documents important natural...
Significance G-quadruplex (GQ)–forming G4 DNA, made of four repeats guanines, is implicated in many important processes. Telomeric GQs are being studied extensively as anticancer drug targets. Because nucleic acid-processing enzymes can exert piconewton forces and be functionally regulated by tension on we used a single-molecule instrument combining fluorescence with mechanical manipulation to study the dynamics human telomeric DNA under physiological levels tension. We observed extreme...
Abstract RNAs begin to fold and function during transcription. Riboswitches undergo cotranscriptional switching in the context of transcription elongation, RNA folding, ligand binding. To investigate how these processes jointly modulate folate stress-sensing Fusobacterium ulcerans ZTP riboswitch, we apply a single-molecule vectorial folding (VF) assay which an engineered superhelicase Rep-X sequentially releases fluorescently labeled riboswitch from heteroduplex 5′-to-3′ direction, at ~60 nt...
Pathologic α-synuclein plays an important role in the pathogenesis of α-synucleinopathies such as Parkinson’s disease (PD). Disruption proteostasis is thought to be central pathologic toxicity; however, molecular mechanism this deregulation poorly understood. Complementary proteomic approaches cellular and animal models PD were used identify characterize interactome. We report that highest biological processes interacted with mice included RNA processing translation initiation. Regulation...
Significance Origin recognition complex (ORC) is required for the initiation of DNA replication. Unlike other ORC components, role human Orc6 in replication remains to be resolved. We identified an unexpected hOrc6, which promote S-phase progression after prereplication assembly and damage response. localizes at fork, accessory factor mismatch repair complex, plays a fundamental genome surveillance during S phase.
Silica fibers are of technological significance in view their applications sensing, photocatalysis, filtration, biological scaffolds, photoluminescence, composites, etc. A combination electrospinning and sol–gel technique has been employed to synthesize inorganic or ceramic sub-micron starting from a novel oligomeric pre-ceramic precursor, Poly(methylhydrosiloxane) (PMHS). The composite were calcined at temperatures the range 550 °C 1400 obtain slica fibers. electrospun derived silica...
Abstract Recent advances in fluorogen-binding “light-up” RNA aptamers have enabled protein-free detection of cells. Detailed biophysical characterization folding G-Quadruplex (GQ)-based light-up such as Spinach, Mango and Corn is still lacking despite the potential implications on their function. In this work we employ single-molecule fluorescence-force spectroscopy to examine mechanical responses Spinach2, i MangoIII MangoIV. Spinach2 unfolds four discrete steps force increased 7 pN refolds...
Abstract A human telomere ends in a single-stranded 3′ tail, composed of repeats T2AG3. G-quadruplexes (GQs) formed from four consecutive have been shown to possess high-structural and mechanical diversity. In principle, GQ can form any that are not necessarily consecutive. To understand the dynamics GQs with positional multiplicity, we studied five six telomeric sequence using combination single molecule FRET optical tweezers. Our results suggest preferential formation at end both K+ Na+...
Kaposi's sarcoma-associated herpesvirus (KSHV) infection modulates the host cell cycle to create an environment optimal for its viral-DNA replication during lytic life cycle. We report here that KSHV vIRF4 targets β-catenin/CBP cofactor and blocks occupancy on cyclin D1 promoter, suppressing G1-S progression enhancing replication. This shows suppresses transition, possibly providing intracellular milieu favorable
The Hippo pathway plays an important role in developmental biology, mediating organ size by controlling cell proliferation through the activity of a core kinase cassette. Multiple upstream events activate pathway, but how each controls this cassette is not fully understood. Activation begins with phosphorylation MST1/2 (also known as STK3/4). Here, using combination vitro biochemistry and cell-based assays, including chemically induced dimerization single-molecule pulldown, we revealed that...
Abstract Single-molecule FRET (smFRET) has become an established tool to study biomolecular structure and dynamics in vitro live cells. We performed a worldwide blind involving 19 labs assess the uncertainty of experiments for proteins with respect measured efficiency histograms, determination distances, detection quantification structural dynamics. Using two protein systems that undergo distinct conformational changes, we obtained less than ± 0.06, corresponding interdye distance precision...
Transcription activator-like effectors (TALEs) bind DNA through an array of tandem 34-residue repeats. How TALE repeat domains wrap around DNA, often extending more than 1.5 helical turns, without using external energy is not well understood. Here, we examine the kinetics binding arrays with varying numbers identical Single molecule fluorescence analysis and deterministic modeling reveal conformational heterogeneity in both free- DNA-bound arrays. Our findings, combined previously identified...
Telomeres are maintained by telomerase or in a subset of cancer cells homologous recombination (HR)-based mechanism, Alternative Lengthening (ALT). The mechanisms regulating telomere-homeostasis ALT remain unclear. We report that replication initiator protein, Origin Recognition Complex-Associated (ORCA/LRWD1), localizing at the ALT-telomeres, modulates HR activity. ORCA's localization to ALT-telomeres is facilitated its interaction SUMOylated shelterin components. loss ORCA ALT-positive...
Sugar cane juice has been harnessed as a green reducing agent for the synthesis of silver nanoparticles, followed by annealing latter into helical and rod-like structures on polymer silicon surfaces respectively.
Abstract The circumsporozoite protein (CSP) forms a dense coat on the surface of sporozoite, infective stage malaria parasite. central repeat region CSP is critical component only licensed vaccine yet little known about its structure or function. We found that sporozoite mutants with severely truncated scrambled repeats have impaired motility due to altered adhesion site formation and dynamics, suggesting provide cohesive environment in which sites can form. hypothesized biophysical...
The mechanistic target of rapamycin (mTOR) signals through the mTOR complex 1 (mTORC1) and 2 to maintain cellular organismal homeostasis. Failure finely tune activity results in metabolic dysregulation disease. While there is substantial understanding molecular events leading mTORC1 activation at lysosome, remarkably little known about what terminates signaling. Here, we show that AAA + ATPase Thorase directly binds mTOR, thereby orchestrating disassembly inactivation mTORC1. disrupts...
The smallest subunit of the human Origin Recognition Complex, hOrc6, is required for DNA replication progression and plays an important role in mismatch repair (MMR) during S-phase. However, molecular details how hOrc6 regulates damage response remain to be elucidated. Orc6 levels are elevated upon specific types genotoxic stress, it phosphorylated at Thr229, predominantly S-phase, oxidative stress. Many pathways, including MMR, mediate repair. Defects MMR linked Lynch syndrome, predisposing...
Abstract Tandem repeats of guanine rich sequences are ubiquitous in the eukaryotic genome. For example, human cells, telomeres at chromosomal ends comprise kilobases T 2 AG 3 . Four such can form G-quadruplexes (GQs). Biophysical studies have shown that GQs formed from four consecutive possess high diversity both their structure and response to tension. In principle, a GQ any may not even be consecutive. order investigate dynamics possessing positional multiplicity, we studied five six...
Abstract Transcription activator-like effectors (TALEs) bind DNA through an array of tandem 34-residue repeats. Here, we examine the kinetics binding for a set TALE arrays with varying numbers identical repeats using single molecule microscopy. Using new deterministic modeling approach, find evidence conformational heterogeneity in both free- and DNA-bound arrays. Combined previous work demonstrating populations partly folded states, our findings reveal functional instability TALE-DNA...