A5004860314- Hemoglobin structure and function
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Prion Diseases and Protein Misfolding
- Mycobacterium research and diagnosis
- Genomics and Phylogenetic Studies
- Supramolecular Self-Assembly in Materials
- Photosynthetic Processes and Mechanisms
- Porphyrin Metabolism and Disorders
- Alzheimer's disease research and treatments
- Neurological diseases and metabolism
- Bacterial Genetics and Biotechnology
- Oral microbiology and periodontitis research
- RNA modifications and cancer
- Tuberculosis Research and Epidemiology
- Trace Elements in Health
- Heme Oxygenase-1 and Carbon Monoxide
- Advanced biosensing and bioanalysis techniques
- Calpain Protease Function and Regulation
- Yersinia bacterium, plague, ectoparasites research
- Porphyrin and Phthalocyanine Chemistry
- Biochemical and Structural Characterization
- CRISPR and Genetic Engineering
- Enzyme Catalysis and Immobilization
- Connexins and lens biology
University of Cambridge
2008-2025
Emory University
2023
University of Westminster
2022
London School of Hygiene & Tropical Medicine
2018-2021
University of London
2018-2021
University College London
2014-2020
MRC Prion Unit
2014-2020
Institute of Biophysics
2011-2017
Chinese Academy of Sciences
2011-2017
National Hospital for Neurology and Neurosurgery
2014-2015
The self-association of proteins into amyloid fibrils offers an alternative to the natively folded state many polypeptides. Although commonly associated with disease, represent natural functional some proteins, such as chaplins from soil-dwelling bacterium Streptomyces coelicolor, which coat aerial mycelium and spores rendering them hydrophobic. We have undertaken a biophysical characterisation five short chaplin peptides ChpD-H probe mechanism by these self-assemble in solution form...
The serine-rich repeat family of fimbriae play important roles in the pathogenesis streptococci and staphylococci. Despite recent attention, their finer structural details precise adhesion mechanisms have yet to be determined. Fap1 (Fimbriae-associated protein 1) is major subunit from Streptococcus parasanguinis plays an essential role fimbrial biogenesis, adhesion, early stages dental plaque formation. Combining multidisciplinary, high resolution studies with biological assays, we provide...
Enzyme immobilization is an important strategy to enhance the stability and recoverability of enzymes facilitate separation from reaction products. However, enzyme purification followed by separate chemical steps allow on a solid support reduces efficiency yield active enzyme. Here we describe polypeptide constructs that self-assemble spontaneously into nanofibrils with fused subunits displayed amyloid fibril surface. We measured steady-state kinetic parameters for appended in situ within...
Abstract We have recently demonstrated a novel anaerobic NADH‐dependent haem breakdown reaction, which is carried out by range of haemoproteins. The Yersinia enterocolitica protein, HemS, the focus further research presented in current paper. Using conventional experimental methods, bioinformatics, and energy landscape theory (ELT), we provide new insight into mechanism process. Of particular interest behavior double phenylalanine gate, opens closes according to relative situations NADH...
Streptomyces bacteria form reproductive aerial hyphae that are covered with a pattern of pairwise aligned fibrils called rodlets. The presence the rodlet layer requires two homologous rodlin proteins, RdlA and RdlB, functional amyloid chaplin ChpA-H. In contrast to redundancy shared among eight chaplins, both RdlB indispensable for establishment this structure. By using comprehensive biophysical approach combined in vivo characterization we found but not RdlA, readily assembles into fibrils....
Mycobacterium tuberculosis, which causes can undergo prolonged periods of non-replicating persistence in the host. The mechanisms underlying this are not fully understood, but translational regulation is thought to play a role. A large proportion mRNA transcripts expressed M. tuberculosis lack canonical bacterial translation initiation signals, little known about implications for fine-tuning translation. Here, we perform ribosome profiling characterize landscape under conditions exponential...
Abstract Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder characterised by accumulation of pathological isoforms the prion protein, PrP. Although cases clinical vCJD are rare, there evidence may be tens thousands infectious carriers in United Kingdom alone. This raises concern about potential for perpetuation infection via medical procedures, particular transfusion contaminated blood products. Accurate biochemical detection crucial to mitigate risk and we have...
Protein nanofibers are emerging as useful biological nanomaterials for a number of applications, but to realize these applications requires cheap and readily available source fibril-forming protein material. We have identified fish lens crystallins feedstock the production report optimized methods their production. Altering conditions formation leads individual assembling into much larger structures. The ability control morphology form higher order structures is crucial step in bottom up...
c-type cytochromes are normally characterized by covalent attachment of the iron cofactor haem to protein through two thioether bonds between vinyl groups and thiol a CXXCH (Cys-Xaa-Xaa-Cys-His) motif. In cells, is an enzyme-catalysed post-translational modification. We have previously shown that co-expression variant Escherichia coli cytochrome b(562) containing haem-binding motif with E. Ccm (cytochrome c maturation) proteins resulted in homogeneous maturation correctly formed cytochrome....
Prion diseases, a group of incurable, lethal neurodegenerative disorders mammals including humans, are caused by prions, assemblies misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents disease, however the structural basis for its protective effect remains unknown. Here we show that alters and constrains backbone conformation preceding β-sheet, stabilising dimer interactions increasing intermolecular hydrogen bonding. It also markedly changes solution...
The system I cytochrome c maturation (Ccm) apparatus has been shown to handle a wide variety of apocytochrome substrates containing the CXnCH heme attachment sequence, where n = 2, 3, or 4 in natural sequences. When 5 6, also appears these correctly, but close inspection reveals that resulting mature cytochromes are mixtures species extra mass. We have used accurate mass spectrometry analyze peptide digests matured Escherichia coli cb562 with 1, 5, 6 and an sulfur is sometimes incorporated...
Abstract Mycobacterium tuberculosis , which causes tuberculosis, expresses a large proportion of leaderless transcripts lacking the canonical bacterial translation initiation signals. The role genes play in physiology this pathogen, can undergo prolonged periods non-replicating persistence host, is currently unknown. We have previously demonstrated that levels transcription increase under conditions nutrient starvation. However, little known about implications for persistent infection. Here,...
Abstract Review: modification of the heme‐binding active site and heme group, protein hybridization domain swapping, de novo design; 113 refs.
The ability of proteins to recognize, bind and manipulate a wide range other molecules lies at the heart virtually every cellular process. In order achieve this, must fold into precise three-dimensional structure. A failure this structure, associated loss protein stability function, results in diseases such as muscular dystrophy cystic fibrosis. addition, misfolding aggregation form fibrillar species is with progression amyloid Alzheimer's Huntington's prion including Creutzfeldt– Jakob...