A5046813999- Molecular Junctions and Nanostructures
- Advanced biosensing and bioanalysis techniques
- Electrochemical Analysis and Applications
- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- Amyotrophic Lateral Sclerosis Research
- Epigenetics and DNA Methylation
- Electrochemical sensors and biosensors
- Enzyme Structure and Function
- Alzheimer's disease research and treatments
- Metal-Catalyzed Oxygenation Mechanisms
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Trace Elements in Health
- Analytical Chemistry and Sensors
- Monoclonal and Polyclonal Antibodies Research
- Nanoparticle-Based Drug Delivery
- Hemoglobin structure and function
- Microbial metabolism and enzyme function
- Receptor Mechanisms and Signaling
- Microbial Metabolic Engineering and Bioproduction
- Computational Drug Discovery Methods
- Blood groups and transfusion
- Various Chemistry Research Topics
- Cancer-related gene regulation
Wyatt Technology (China)
2024
University of California, Santa Barbara
2016-2023
University of California System
2019
Santa Barbara City College
2019
Stockholm University
2011-2013
The electrochemical aptamer-based (E-AB) sensing platform appears to be a convenient (rapid, single-step, and calibration-free) modular approach measure concentrations of specific molecules (irrespective their chemical reactivity) directly in blood even situ the living body. Given these attributes, may thus provide significant opportunities render therapeutic drug monitoring (the clinical practice which dosing is adjusted response plasma measurements) as frequent measurement sugar has become...
The ability to monitor drugs, metabolites, hormones, and other biomarkers in situ the body would greatly advance both clinical practice biomedical research. To this end, we are developing electrochemical aptamer-based (EAB) sensors, a platform technology able perform real-time, vivo monitoring of specific molecules irrespective their chemical or enzymatic reactivity. An important obstacle deployment EAB sensors challenging environments found living is signal drift, whereby sensor decreases...
Although superoxide dismutase 1 (SOD1) stands out as a relatively soluble protein in vitro, it can be made to fibrillate by mechanical agitation. The mechanism of this fibrillation process is yet poorly understood, but attains considerable interest due SOD1’s involvement the neurodegenerative disease amyotrophic lateral sclerosis (ALS). In study, we map apoSOD1 from how competes with global folding events at increasing concentrations urea: We determine lag time (τ ) and maximum growth rate...
The efficiency with which square-wave voltammetry differentiates faradic and charging currents makes it a particularly sensitive electroanalytical approach, as evidenced by its ability to measure nanomolar or even picomolar concentrations of electroactive analytes. Because the relative complexity potential sweep uses, however, extraction detailed kinetic mechanistic information from data remains challenging. In response, we demonstrate here numerical approach can be used determine electron...
Demetallation of the homodimeric enzyme Cu/Zn-superoxide dismutase (SOD1) is known to unleash pronounced dynamic motions in long active-site loops that comprise almost a third folded structure. The resulting apo species, which shows increased propensity aggregate, stands out as prime disease precursor amyotrophic lateral sclerosis (ALS). Even so, detailed structural properties apoSOD1 framework have remained elusive and controversial. In this study, we examine interplay between central...
Surface charges of proteins have in several cases been found to function as “structural gatekeepers,” which avoid unwanted interactions by negative design, for example, the control protein aggregation and binding. The question is then if side-chain charges, due their desolvation penalties, play a corresponding role folding avoiding competing, misfolded traps? To find out, we removed all 32 from 101-residue S6 Thermus thermophilus . results show that charge-depleted variant not only retains...
Here we demonstrate a new class of reagentless, single-step sensors for the detection proteins and peptides that is electrochemical analog fluorescence polarization (fluorescence anisotropy), versatile optical approach widely employed to this same end. Our consist redox-reporter-modified protein (the "receptor") site-specifically anchored an electrode via short, flexible polypeptide linker. Interaction receptor with its binding partner alters efficiency which reporter approaches surface,...
Electrochemical sensors are major players in the race for improved molecular diagnostics due to their convenience, temporal resolution, manufacturing scalability, and ability support real-time measurements. This is evident ever-increasing number of health-related electrochemical sensing platforms, ranging from single-measurement point-of-care devices wearable supporting immediate continuous monitoring. In need such systems rapidly process large data volumes, we describe here an open-source,...
Abstract The ability to monitor drug and biomarker concentrations in the body with high frequency real time would revolutionize our understanding of biology capacity personalize medicine. few vivo molecular sensors that currently exist, however, all rely on specific chemical or enzymatic reactivity their targets thus are not generalizable. In response, we demonstrate here an electrochemical sensing architecture based binding‐induced protein folding is 1) independent its targets, 2)...
The origin and biological role of dynamic motions folded enzymes is not yet fully understood. In this study, we examine the molecular determinants for within β-barrel superoxide dismutase 1 (SOD1), which previously were implicated in allosteric regulation protein maturation also pathological misfolding neurodegenerative disease amyotrophic lateral sclerosis. Relaxation-dispersion NMR, hydrogen/deuterium exchange, crystallographic data show that are induced by buried H43 side chain, connects...
Lipid nanoparticles (LNPs) are the most advanced delivery system currently available for RNA therapeutics. Their development has accelerated rapidly since success of Patisiran, first siRNA-LNP therapeutic, and SARS-CoV-2 mRNA vaccines that emerged during COVID-19 pandemic. Designing LNPs with specific targeting, high potency, minimal side effects is crucial their successful clinical use. However, our understanding how composition mixing methods influence structure, biophysical properties,...
The faster a disease is diagnosed, the sooner treatment can be initiated, motivating drive to replace standard laboratory techniques with point-of-care technology. Here we describe development of an E-DNA sensor for rapid measurement anti-syphilis antibodies.
Whereas proteins generally remain stable upon interaction with biological surfaces, they frequently unfold on and adhere to artificial surfaces. Understanding the physicochemical origins of this discrepancy would facilitate development protein-based sensors other technologies that require surfaces do not compromise protein structure function. To date, however, only a small number such have been reported, physics why these support functional biomolecules while others has established. Thus...
Despite the importance of protein-surface interactions in both biology and biotechnology, our understanding their origins is limited due to a paucity experimental studies thermodynamics behind such interactions. In response, we have characterized extent which interaction with chemically well-defined macroscopic surface alters stability protein L. To do so, site-specifically attached redox-reporter-modified variant hydroxy-terminated monolayer on gold then used electrochemistry monitor its...
The molecular determinants for selectivity of ligand binding to membrane receptors are key importance the understanding cellular signalling, as well rational therapeutic intervention. In present study, we target interaction between κ opioid receptor ( KOR ) and its native peptide dynorphin A D yn using solution state NMR spectroscopy, which is generally made difficult by sheer size bound receptors. Our method based on ‘transplantation’ an extracellular loop into a ‘surrogate’ scaffold; in...
The physics of proteins interacting with surfaces can differ significantly from those seen when the same are free in bulk solution. As an example, we describe here extent to which site-specific attachment a chemically well-defined macroscopic surface alters ability several stabilizing and destabilizing cosolutes modulate protein folding thermodynamics. We determined this via guanidinium denaturations performed presence varying concentrations were either site-specifically attached...
Abstract Strand-separation is emerging as a novel DNA recognition mechanism but the underlying mechanisms and quantitative contribution of strand-separation to fidelity remain obscure. The bacterial adenine methyltransferase, CcrM, recognizes 5′GANTC′3 sequences through with unusually high selectivity. To explore this mechanism, we incorporated Pyrrolo-dC into cognate noncognate monitor kinetics used tryptophan fluorescence follow protein conformational changes. Both signals are biphasic...
Abstract The ability to monitor drug and biomarker concentrations in the body with high frequency real time would revolutionize our understanding of biology capacity personalize medicine. few vivo molecular sensors that currently exist, however, all rely on specific chemical or enzymatic reactivity their targets thus are not generalizable. In response, we demonstrate here an electrochemical sensing architecture based binding‐induced protein folding is 1) independent its targets, 2)...
Abstract Lipid nanoparticles (LNPs) are the most advanced delivery system currently available for RNA therapeutics. Their development has accelerated since success of Patisiran, first siRNA-LNP therapeutic, and mRNA vaccines that emerged during COVID-19 pandemic. Designing LNPs with specific targeting, high potency, minimal side effects is crucial their successful clinical use. These characteristics have been improved through microfluidic platforms, which enhanced efficacy uniformity LNP...
Abstract Despite the importance of protein–surface interactions in both biology and biotechnology, our understanding their origins is limited due to a paucity experimental studies thermodynamics behind such interactions. In response, we have characterized extent which interaction with chemically well‐defined macroscopic surface alters stability protein L. To do so, site‐specifically attached redox‐reporter‐modified variant hydroxy‐terminated monolayer on gold then used electrochemistry...