A5055407024- Growth Hormone and Insulin-like Growth Factors
- Immune Cell Function and Interaction
- Enzyme Structure and Function
- Alzheimer's disease research and treatments
- CAR-T cell therapy research
- Bacterial biofilms and quorum sensing
- Bacterial Identification and Susceptibility Testing
- Computational Drug Discovery Methods
- Drug Transport and Resistance Mechanisms
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Advanced Proteomics Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Cholinesterase and Neurodegenerative Diseases
- Mass Spectrometry Techniques and Applications
- Protein purification and stability
- Microbial Natural Products and Biosynthesis
- Biosensors and Analytical Detection
- Inorganic and Organometallic Chemistry
- Chemical Reactions and Mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Genetic Syndromes and Imprinting
- Photoacoustic and Ultrasonic Imaging
- Metabolism, Diabetes, and Cancer
University of California, Los Angeles
2022-2024
Concept Life Sciences (United Kingdom)
2024
Hudson Institute
2023
The Japanese Society of Gastroenterological Surgery
2023
Hiroshima University Hospital
2023
Iwate Medical University
2023
University of Nottingham
2019-2020
Sunny BioDiscovery (United States)
2020
University of Oxford
2005-2018
Amgen (United States)
2008-2018
Crystallization trials at the Division of Structural Biology in Oxford are now almost exclusively carried out using a high-throughput workflow implemented Protein Production Facility. Initial crystallization screening is based on nanolitre-scale sitting-drop vapour-diffusion experiments (typically 100 nl protein plus reservoir solution per droplet) which use standard kits and 96-well plates. For 294 K barcoded plates entered into an automated storage system with fully integrated imaging...
The murine molecule dectin-1 (known as the beta-glucan receptor in humans) is an immune cell surface implicated immunological defense against fungal pathogens. Sequence analysis has indicated that extracellular domain a C-type lectin-like domain, and functional studies have established it binds beta-glucans. We report several crystal structures, including high-resolution structure 2.8 angstroms resolution which short soaked natural trapped lattice. In vitro characterization of presence its...
Using fragment-based screening of a focused fragment library, 2-aminoquinoline 1 was identified as an initial hit for BACE1. Further SAR development supported by X-ray structures BACE1 cocrystallized with various ligands and molecular modeling studies to expedite the discovery potent compounds. These strategies enabled us integrate C-3 side chain on extending deep into P2′ binding pocket enhancing ligand's potency. We were able improve potency subnanomolar range, over 106-fold more than (900...
Accumulation of extracellular adenosine within the microenvironment is a strategy exploited by tumors to escape detection immune system. Adenosine signaling through 2A receptor (A2AR) on cells elicits range immunosuppressive effects which promote tumor growth and limit efficacy checkpoint inhibitors. Preclinical data with A2AR inhibitors have demonstrated regressions in mouse models rescuing T cell function; however, mechanism role other has not been fully elucidated.We report here...
The field of T cell-based and chimeric antigen receptor (CAR)-engineered (CAR-T) antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) tumor-associated immunosuppression, have proven to be roadblocks widespread adoption implementation. Recent innate immune CAR therapy opened several doors for expansion this therapy, especially it relates allogeneic cell sources solid tumor infiltration. This study...
An initial tranche of results from day-to-day use a robotic system for setting up 100 nl-scale vapour-diffusion sitting-drop protein crystallizations has been surveyed. The database over 50 unrelated samples represents snapshot projects currently at the stage crystallization trials in Oxford research groups and as such encompasses broad range proteins. indicate that nanolitre-scale methodology consistently identifies more conditions than traditional hand-pipetting-style methods; however,...
The junctional adhesion molecules (JAMs) have been recently described as interendothelial and integrin ligands. Here we show that JAM-B JAM-C undergo heterophilic interaction in cell-cell contacts is recruited stabilized complexes by JAM-B. In addition, soluble dissociates homodimers to form JAM-B/JAM-C heterodimers. This suggests the affinity of monomers dimers higher for than JAM-C. Using antibodies against JAM-C, formation heterodimers can be abolished. liberates from its vascular binding...
A protocol for setting up nanolitre sitting-drop vapour-diffusion experiments is reported. The procedure uses standard crystallization screening kits and 96-well plates. Reservoir solutions are transferred from 96-deep-well blocks to plates in a single step with Robbins-Hydra pipettor. Nanolitre droplets of protein as well reservoir solution dispensed by Cartesian pipetting instrument. Experiments have been carried out characterize the performance this Adaptations Cartesian, which include an...
Abstract Invariant NKT cells (iNKT cells) recognize CD1d/glycolipid complexes. We demonstrate that the nonglycosidic compound threitolceramide efficiently activates iNKT cells, resulting in dendritic cell (DC) maturation and priming of Ag-specific T B cells. Threitolceramide-pulsed DCs are more resistant to cell-dependent lysis than α-galactosylceramide-pulsed due weaker affinity human TCR for CD1d/ CD1d/α-galactosylceramide stimulated with also recover quickly from activation-induced...
A series of potent hydroxyethyl amine (HEA) derived inhibitors β-site APP cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a benzodioxolane analogues that possessed improved metabolic stability increased oral bioavailability. Subsequent efforts focused on improving exposure by limiting susceptibility Pgp-mediated efflux an inhibitor which demonstrated robust sustained reduction β-amyloid (Aβ) in Sprague–Dawley rats...
Transient-receptor-potential melastatin 8 (TRPM8), the predominant mammalian cold-temperature thermosensor, is a nonselective cation channel expressed in subpopulation of sensory neurons peripheral nervous system, including nerve circuitry implicated migraine pathogenesis: trigeminal and pterygopalatine ganglia. Genomewide association studies have identified an between TRPM8 reduced risk migraine. This disclosure focuses on medicinal-chemistry efforts to improve druglike properties initial...
Secondary ion mass spectrometry (SIMS) is gaining popularity for molecular imaging in the life sciences because it label-free and allows two three dimensions. The recent introduction of OrbiSIMS has significantly improved utility biological through combining subcellular spatial resolution with high-performance Orbitrap spectrometry. SIMS instruments operate high-vacuum, samples are typically analyzed a freeze-dried state. Consequently, structural information may not be well-preserved. We...
Chemotaxonomic studies were performed on some gram-positive coryneform bacteria of uncertain taxonomic position isolated from poultry deep litter. On the basis present chemical and previous phenetic studies, we suggest that these be classified in a new genus, Brachybacterium, as Brachybacterium faecium gen. nov., sp. nov. The type strain is NCIB 9860.
The human C-type lectin-like molecule CLEC-2 is expressed on the surface of platelets and signaling through causes platelet activation aggregation. a receptor for platelet-aggregating snake venom protein rhodocytin. It also newly identified co-receptor immunodeficiency virus type 1 (HIV-1). An endogenous ligand has not yet been identified. We have solved crystal structure extracellular domain to 1.6-A resolution, key structural features involved in binding. A semi-helical loop region...
Type III secretion systems are found in many Gram-negative bacteria. They activated by contact with eukaryotic cells and inject virulence proteins inside them. Host cell detection requires a protein complex located at the tip of device's external injection needle. The Shigella (TC) is composed IpaD, hydrophilic protein, IpaB, hydrophobic which later forms part pore host membrane. Here we used labelling crosslinking methods to show that TCs from ΔipaB strain contain five IpaD subunits while...
A variety of natural surfaces exhibit antibacterial properties; as a result, significant efforts in the past decade have been dedicated toward fabrication biomimetic that can help control biofilm growth. Examples such include rose petals, which possess hierarchical structures like micropapillae measuring tens microns and nanofolds range size 700 ± 100 nm. We duplicated on petal via simple UV-curable nanocasting technique tested efficacy these artificial preventing growth using clinically...