- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- Protein Structure and Dynamics
- Synthetic Organic Chemistry Methods
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Growth Hormone and Insulin-like Growth Factors
- Chemical Synthesis and Analysis
- Quinazolinone synthesis and applications
- RNA and protein synthesis mechanisms
- HER2/EGFR in Cancer Research
- Biochemical and Molecular Research
- Photosynthetic Processes and Mechanisms
- Click Chemistry and Applications
- Cryospheric studies and observations
- Cellular transport and secretion
- Burkholderia infections and melioidosis
- Chronic Myeloid Leukemia Treatments
- Analytical Chemistry and Chromatography
- Platelet Disorders and Treatments
- Landslides and related hazards
- Biochemical and Structural Characterization
- Retinal Development and Disorders
- Protist diversity and phylogeny
University of Manchester
2021-2025
University of Bristol
2015-2024
Mayo Clinic Health System
2020
Newcastle University
2020
Group for Research in Decision Analysis
2018-2020
Duke Medical Center
2019
British Geological Survey
2019
At Bristol
2017
The London College
2017
University College London
2007-2017
TA (toxin-antitoxin) systems are widely distributed amongst bacteria and associated with the formation of antibiotic tolerant (persister) cells that may have involvement in chronic recurrent disease. We show overexpression Burkholderia pseudomallei HicA toxin causes growth arrest increases number persister to ciprofloxacin or ceftazidime. Furthermore, our data persistence towards ceftazidime can be differentially modulated depending on level induction expression. Deleting hicAB locus from B....
Two bioactive cyclic dipeptides, cyclo(L-Pro-L-Tyr) and cyclo(D-Pro-L-Tyr), were isolated from the culture broth of Streptomyces sp. strain 22-4 tested against three economically important plant pathogens, Xanthomonas axonopodis pv. citri, Ralstonia solanacearum Clavibacter michiganensis. Both dipeptides active X. citri R. Solanacearum with MIC 31.25 μg/mL. No activity could be observed C.
Abstract. Subglacial roughness can be determined at a variety of length scales from radio-echo sounding (RES) data either via statistical analysis topography or inferred basal radar scattering. Past studies have demonstrated that subglacial terrain exhibits self-affine (power law) scaling behaviour, but existing scattering models do not take this into account. Here, using RES northern Greenland, we introduce framework enables consistent integration topographic-scale with the electromagnetic...
The Hippo pathway is an important regulator of cell growth, proliferation, and migration. TEAD transcription factors, which lie at the core pathway, are essential for regulation organ growth wound repair. Dysregulation its regulatory cofactor Yes-associated protein (YAP) have been implicated in numerous human cancers hyperproliferative pathological processes. Hence, YAP-TEAD complex a promising therapeutic target. Here, we use silico molecular docking using Bristol University Docking Engine...
Carbohydrate receptors with a chiral framework have been generated by combining tetra-aminopyrene and C3-symmetrical triamine via isophthalamide spacers bearing water-solubilising groups. These "synthetic lectins" are the first to show enantiodiscrimination in aqueous solution, binding N-acetylglucosamine (GlcNAc) 16 : 1 enantioselectivity. They also exceptional affinities. GlcNAc is bound Ka up 1280 M-1, more than twice that measured for previous synthetic lectins, three times value wheat...
The 19-mer synthetic peptide known as R5 has been used widely in studies of peptide-driven silica condensation. Despite this, the structure and function have not yet fully characterized. Here, we present a systematic study silicification focusing on three key variables: concentration peptide, precursor silicic acid, solution pH. Additionally, first secondary presence absence acid introduce one-dimensional two-dimensional NMR to probe both higher-order aggregation. We find that R5-directed is...
Platelets, small hemostatic blood cells, are derived from megakaryocytes. Both bone marrow and lung principal sites of thrombopoiesis although underlying mechanisms remain unclear. Outside the body, however, our ability to generate large number functional platelets is poor. Here we show that perfusion megakaryocytes ex vivo through mouse vasculature generates substantial platelet numbers, up 3000 per megakaryocyte. Despite their size, able repeatedly passage vasculature, leading enucleation...
The identification of stem cell-specific proteins and the elucidation their novel regulatory pathways may help in development protocols for control self-renewal differentiation cell-based therapies. Nucleostemin is a recently discovered nucleolar protein predominantly associated with proliferating rat neural embryonic cells, some human cancer cell lines. A comprehensive study nucleostemin adult bone marrow cells lacking. aim was to determine if synthesized by analyze its expression during...
Photocontrol of Bcl-x(L) binding affinity has been achieved by using short BH3 domain peptides for Bak(72-87) and Bid(91-111) alkylated with an azobenzene crosslinker through two cysteine residues different sequence spacings. The power to control the conformation hence peptide structure was demonstrated CD UV/Vis spectroscopy. determined in their dark-adapted irradiated states fluorescence anisotropy measurements, use spacings allowed either activation or deactivation activities these...
The role of facial vibrissae (whiskers) in the behavior terrestrial mammals is principally as a supplement or substitute for short-distance vision. Each whisker array functions mechanical transducer, conveying forces applied along shaft to mechanoreceptors follicle at base. Subsequent processing mechanoreceptor output trigeminal nucleus and somatosensory cortex allows high accuracy discriminations object distance, direction, surface texture. whiskers are tapered approximately circular cross...
Color vision, originating with opponent processing of spectrally distinct photoreceptor signals, plays important roles in animal behavior.1Price T.D. Sensory drive, color, and color vision.Am. Nat. 2017; 190: 157-170Crossref PubMed Scopus (32) Google Scholar, 2Spitschan M. Lucas R.J. Brown T.M. Chromatic clocks: opponency non-image-forming visual function.Neurosci. Biobehav. Rev. 78: 24-33Crossref (23) 3Baden T. Osorio D. The retinal basis vertebrate vision.Annu. Vis. Sci. 2019; 5:...
The electron-conducting circuitry of life represents an as-yet untapped resource exquisite, nanoscale biomolecular engineering. Here, we report the characterization and structure a de novo diheme "maquette" protein, 4D2, which subsequently use to create expanded, modular platform for heme protein design. A well-folded monoheme variant was created by computational redesign, then utilized experimental validation continuum electrostatic redox potential calculations. This demonstrates how...
Abstract Nature has evolved diverse electron transport proteins and multiprotein assemblies essential to the generation transduction of biological energy. However, substantially modifying or adapting these for user‐defined applications gain fundamental mechanistic insight can be hindered by their inherent complexity. De novo protein design offers an attractive route stripping away this confounding complexity, enabling us probe workings bioenergetic systems, while providing robust, modular...
Vertebrate retinas share a basic blueprint comprising 5 neuronal classes arranged according to common wiring diagram. Yet, vision is aligned with species differences in behavior and ecology, raising the question of how evolution acts on this circuit adjust its computational characteristics. We address that problem by comparing thalamic visual code retinal cell composition closely related occupying different niches: Rhabdomys pumilio, which are day-active murid rodents, nocturnal laboratory...
According to the "combi-targeting" concept, EGFR tyrosine kinase (TK) inhibitory potency of compounds termed "combi-molecules" is critical for selective growth inhibition tumor cells with disordered expression or its closest family member erbB2. Here we report on optimization TK combi-molecules nitrosourea class by comparison their aminoquinazoline and ureidoquinazoline precursors. This led discovery a new structural parameter that influences potency, i.e., torsion angle between plane...
Preparative capillary gas chromatography (pcGC) is widely used for the isolation of single compounds radiocarbon determinations. While being effective at isolating compounds, there are still genuine concerns relating to contamination associated with procedure, such as incomplete removal solvent recover isolated from traps and cross-contamination, which can lead erroneous 14C Herein we describe new approaches identifying removing these two sources contamination. First, replaced common "U"...
Abstract. The subglacial environment of the Greenland Ice Sheet (GrIS) is poorly constrained both in its bulk properties, for example geology, presence sediment, and water, interfacial conditions, such as roughness bed rheology. There is, therefore, limited understanding how spatially heterogeneous properties relate to ice-sheet motion. Here, via analysis 2 decades radio-echo sounding data, we present a new systematic beneath GrIS. We use two independent methods quantify roughness: first,...
Patients with COVID-19 are at increased risk of thrombosis, which is associated altered platelet function and coagulopathy, contributing to excess mortality.To characterize the mechanism in patients.The proteome, functional responses, platelet-neutrophil aggregates were compared between patients hospitalized healthy control subjects using tandem mass tag proteomic analysis, Western blotting, flow cytometry.COVID-19 showed a different profile protein expression (858 5773 quantified). Levels...
The actinorhodin (act) synthase acyl carrier protein (ACP) from Streptomyces coelicolor plays a central role in polyketide biosynthesis. Polyketide intermediates are bound to the free sulfhydryl group of phosphopantetheine arm that is covalently linked conserved serine residue holo form ACP. solution NMR structures both apo and forms ACP reported, which represents first high resolution comparison these two an Ensembles twenty were calculated yielded atomic root mean square deviations...