- Protein Structure and Dynamics
- Molecular spectroscopy and chirality
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- Chemical Synthesis and Analysis
- Liquid Crystal Research Advancements
- Photosynthetic Processes and Mechanisms
- Glycosylation and Glycoproteins Research
- Synthesis and Properties of Aromatic Compounds
- Spectroscopy and Quantum Chemical Studies
- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Toxin Mechanisms and Immunotoxins
- Proteoglycans and glycosaminoglycans research
- Advanced biosensing and bioanalysis techniques
- Alzheimer's disease research and treatments
- Protein Interaction Studies and Fluorescence Analysis
- Crystallography and molecular interactions
- Surface Chemistry and Catalysis
- Supramolecular Self-Assembly in Materials
- Heat shock proteins research
- Hemoglobin structure and function
- Microfluidic and Capillary Electrophoresis Applications
- Monoclonal and Polyclonal Antibodies Research
- Bacterial Genetics and Biotechnology
Diamond Light Source
2016-2025
Ludwig-Maximilians-Universität München
2023
Rutherford Appleton Laboratory
2009-2021
Didcot Community Hospital
2014-2020
Research Complex at Harwell
2020
Chilton Medical Center
2019
Oxfam
2015
University of Liverpool
2009-2014
Mary Lyon Centre at MRC Harwell
2014
King's College London
1997-2006
Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered fundamental molecular pathway, which includes ligand-dependent activation ectopically expressed latrophilin 1 possibly other G-protein coupled receptors leading to increased translation exocytosis the receptor Tim-3 its ligand galectin-9. This occurs in protein kinase C mTOR...
The integration of luminescence and chirality in easy-scalable metal-organic frameworks gives rise to the development advanced luminescent sensors. To date, synthesis chiral is poorly predictable their primarily originates from components that constitute frameworks. By contrast, introduction into pores has not been explored best our knowledge. Here, we demonstrate can be introduced an anionic Zn-based framework via simple cation exchange, yielding dual centers comprised ligand Tb3+ ions,...
<i>In vivo</i> activation of client proteins by Hsp90 depends on its ATPase-coupled conformational cycle and interaction with a variety co-chaperone proteins. For some the Sti1/Hop/p60 acts as "scaffold," recruiting Hsp70 bound to early in suppressing ATP turnover during loading phase. Recruitment protein kinase clients complex appears involve specialized co-chaperone, Cdc37p/p50<sup>cdc37</sup>, whose binding is mutually exclusive Sti1/Hop/p60. We now show that like Sti1/Hop/p60, also...
ATP hydrolysis by the Hsp90 molecular chaperone requires a connected set of conformational switches triggered binding to N-terminal domain in dimer. Central this is segment structure, which closes like "lid" over bound ATP, promoting dimerization and assembly competent active site. mutants that influence these have strong effects on ATPase activity. activity specifically regulated co-chaperones, directly switches. Here we analyzed effect mutations (using isothermal titration calorimetry...
Human cancer cells operate a variety of effective molecular and signalling mechanisms which allow them to escape host immune surveillance thus progress the disease. We have recently reported that receptor Tim-3 its natural ligand galectin-9 are involved in human acute myeloid leukaemia cells. These use neuronal latrophilin 1 (LPHN1) fibronectin leucine rich transmembrane protein 3 (FLRT3, possibly other ligands) trigger pathway. hypothesised Tim-3-galectin-9 pathway may be different origins....
We measure the structural and stability changes of proteins at nanomolar concentration upon interaction with nanoparticles. Using synchrotron radiation circular dichroism (SRCD), we a decrease 6 °C in thermal unfolding human serum albumin silver nanoparticles while this does not happen gold. The use SRCD allows measuring critical parameters on protein-nanoparticle interactions, it will provide experimental data relative key biological for nanotoxicology.
The effect of spin polarization in conduction and electric field-induced was measured for double-stranded DNA oligonucleotides oligopeptides different lengths. These measurements were conducted using magnetic contact AFM, spin-dependent electrochemistry, polarization, magnetoresistance studies. It established that the through chiral molecules depends on voltage applied with a power d, when d is larger than unity, there threshold conducting each polarizations. In addition, no flipping during...
Polymer thin films that emit and absorb circularly polarised light have been demonstrated with the promise of achieving important technological advances; from efficient, high-performance displays, to 3D imaging all-organic spintronic devices. However, origin large chiroptical effects in such has, until now, remained elusive. We investigate emergence phenomena achiral polymers blended a chiral small-molecule additive (1-aza[6]helicene) intrinsically chiral-sidechain using combination...
Acute myeloid leukemia (AML), a blood/bone marrow cancer, is severe and often fatal malignancy. AML cells are capable of impairing the anti-cancer activities cytotoxic lymphoid cells. This includes inactivation natural killer (NK) killing T lymphocytes. Here we report for first time that V-domain Ig-containing suppressor cell activation (VISTA), protein expressed by cells, recognizes galectin-9 secreted as ligand. Importantly, found soluble VISTA released enhances effect galectin-9, most...
Organic light-emitting diodes (OLEDs) that are able to emit high levels of circularly polarized (CP) light hold significant promise in numerous future technologies. Such devices require chiral emissive materials enable CP electroluminescence. However, the vast majority current OLED emitter classes, including state-of-the-art triplet-harvesting thermally activated delayed fluorescence (TADF) materials, produce very low Here a host-guest strategy allows for energy transfer between polymer host...
The connection between magnetic field induced optical activity and chirality has a rich complicated history. Although the broken inversion symmetry of chiral molecules generates ‘natural’ activity, is generated by breaking time reversal symmetry. As result, molecular not expected to influence phenomena, such as Faraday rotation. Here we show that supramolecular assembly polymers can result in large effect. This strong rotation, which amongst highest value known for organic materials,...
Highly concentrated solutions of asymmetric semiconductor magic-sized clusters (MSCs) cadmium sulfide, selenide, and telluride were directed through a controlled drying meniscus front, resulting in the formation chiral MSC assemblies. This process aligned their transition dipole moments produced chiroptic films with exceptionally strong circular dichroism. G-factors reached magnitudes as high 1.30 for drop-cast 1.06 patterned films, approaching theoretical limits. By controlling evaporation...
V-domain Ig-containing suppressor of T cell activation (VISTA) is a unique immune checkpoint protein, which was reported to display both receptor and ligand activities. However, the mechanisms regulation VISTA activity functions by factors tumour microenvironment (TME) remain unclear understanding these processes required in order develop successful personalised cancer immunotherapeutic strategies approaches. Here we report for very first time that interacts with another protein galectin-9...
A palladium porphyrin has been covalently linked to a chiral lanthanide complex and effectively sensitises near-IR emission from Nd Yb; sensitisation is enhanced in the absence of oxygen presence nucleic acid.
Modulation of the frequency and polarisation emitted light is achieved with structurally rigid tetraamide complexes lanthanides (Ln = Eu, Tb, Yb Dy; Ar Ph, p-X-Ph; X Br, CN, CO2Me; see picture). The configuration at C determines metal-centred helicity, overall quantum yields up to 0.81 were measured in D2O.
Synchrotron radiation circular dichroism (SRCD) is a well established technique in structural biology. The first UV-VIS beamline, dedicated to dichroism, at Diamond Light Source Ltd, third-generation synchrotron facility south Oxfordshire, UK, has recently become operational and it now available for the user community. Herein main characteristics of B23 SRCD ancillary facilities users, some recent advances achieved are summarized.
The functions of a large number (>435) extracellular regulatory proteins are controlled by their interactions with heparan sulfate (HS). In the case fibroblast growth factors (FGFs), HS binding determines transport between cells and is required for assembly high affinity signaling complexes cognate FGF receptor. However, specificity interaction FGFs still debated. Here, we use panel (FGF-1, FGF-2, FGF-7, FGF-9, FGF-18, FGF-21) spanning five subfamilies to probe specificities at different...
The B23 Circular Dichroism beamline at Diamond Light Source has been operational since 2009 and seen visits from more than 200 user groups, who have generated large amounts of data. Based on the experience overseeing users' progress B23, four key areas requiring most assistance are identified: planning experiments note-keeping; designing titration experiments; processing analysis collected data; production experimental reports. To streamline these processes an integrated software package...
H‐NS is a major component of the bacterial nucleoid, involved in condensing and packaging DNA modulating gene expression. The mechanism by which this achieved remains unclear. Genetic data show that biological properties are influenced its oligomerization properties. We have applied variety biophysical techniques to study structural basis protein from Salmonella typhimurium . N‐terminal 89 amino acids responsible for oligomerization. first 64 residues form trimer dominated an α‐helix, likely...
The β-lactam antibiotic ceftriaxone was suggested as a therapeutic agent in several neurodegenerative disorders, either for its ability to counteract glutamate-mediated toxicity, cerebral ischemia, or enhance the degradation of misfolded proteins, Alexander's disease. Recently, efficacy neuroprotection dopaminergic neurons rat model Parkinson's disease documented. However, which characteristics mediate effects remains unclear. Since, at molecular level, neuronal α-synuclein inclusions and...