A5045988291- Advanced Electron Microscopy Techniques and Applications
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Advanced biosensing and bioanalysis techniques
- Photosynthetic Processes and Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Bacteriophages and microbial interactions
- Quantum Dots Synthesis And Properties
- Supramolecular Self-Assembly in Materials
- Chemical Synthesis and Analysis
- Force Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- Microbial Natural Products and Biosynthesis
- RNA Interference and Gene Delivery
- Lipid Membrane Structure and Behavior
- Cell Image Analysis Techniques
- Protein Structure and Dynamics
- Marine Sponges and Natural Products
- Algorithms and Data Compression
- Photoreceptor and optogenetics research
- Genomics and Phylogenetic Studies
- Erythrocyte Function and Pathophysiology
- Endoplasmic Reticulum Stress and Disease
- Medical Image Segmentation Techniques
- Electron and X-Ray Spectroscopy Techniques
University of Bristol
2015-2024
Health & Life (Taiwan)
2023
An ability to mimic the boundaries of biological compartments would improve our understanding self-assembly and provide routes new materials for delivery drugs biologicals development protocells. We show that short designed peptides can be combined form unilamellar spheres approximately 100 nanometers in diameter. The design comprises two, noncovalent, heterodimeric homotrimeric coiled-coil bundles. These are joined back render two complementary hubs, which when mixed hexagonal networks...
Abstract Some insects, such as dragonflies, have evolved nanoprotrusions on their wings that rupture bacteria contact. This has inspired the design of antibacterial implant surfaces with insect-wing mimetic nanopillars made synthetic materials. Here, we characterise physiological and morphological effects titanium bacteria. The induce deformation penetration Gram-positive Gram-negative bacterial cell envelope, but do not or lyse They can also inhibit division, trigger production reactive...
ABSTRACT Replication of positive-sense RNA viruses is associated with the rearrangement cellular membranes. Previous work on infection tissue culture cell lines betacoronaviruses mouse hepatitis virus and severe acute respiratory syndrome coronavirus (SARS-CoV) showed that they generate double-membrane vesicles (DMVs) convoluted membranes as part a reticular membrane network. Here we describe detailed study rearrangements induced by avian gammacoronavirus infectious bronchitis (IBV) in...
The COPII complex mediates the selective incorporation of secretory cargo and relevant machinery into budding vesicles at specialised sites on endoplasmic reticulum membrane called transitional ER (tER). Here, we show using confocal microscopy, immunogold labelling ultrathin cryosections electron tomography that in human cells steady state, Sec16 localises to cup-like structures tER are spatially distinct from localisation other coat components. We defines tER, whereas Sec23-Sec24...
Nature presents various protein fibers that bridge the nanometer to micrometer regimes. These structures provide inspiration for de novo design of biomimetic assemblies, both address difficulties in studying and understanding natural systems, routes new biomaterials with potential applications nanotechnology medicine. We have designed a self-assembling fiber system, SAFs, which two small α-helical peptides are programmed form dimeric coiled coil assemble controlled manner. The resulting tens...
Abstract A series of glycan‐coated quantum dots were prepared to probe the effect glycan presentation in intracellular localization HeLa and SV40 epithelial cells. We show that density mostly impacts on cell toxicity, whereas type affects uptake localization. Moreover, we lactose can act as a “Trojan horse” bi‐functionalized QDs help delivery other non‐internalizable moieties largely avoid endosomal/lysosomal degradative pathway.
Cytotoxic T lymphocytes (CTLs) are highly effective serial killers capable of destroying virally infected and cancerous targets by polarized release from secretory lysosomes. Upon target contact, the CTL centrosome rapidly moves to immunological synapse, focusing microtubule-directed at this point [1-3]. Striking similarities have been noted between polarization synapse basal body docking during ciliogenesis [1, 4-8], suggesting that centrosomes might dock with plasma membrane killing, in a...
The human glomerulus is the primary filtration unit of kidney, and contains Glomerular Filtration Barrier (GFB). GFB had been thought to comprise 3 layers - endothelium, basement membrane podocyte foot processes. However, recent studies have suggested that at least two additional contribute function GFB, endothelial glycocalyx on vascular side, sub-podocyte space urinary side. To investigate structure these difficult as it requires three-dimensional reconstruction delicate sub-microscopic...
A de novo topology of virus-like assembly is reported. The design a trifaceted coiled-coil peptide helix, which self-assembles into ultrasmall, monodisperse, anionic shells that encapsulate and transfer both RNA DNA human cells. Unlike existing artificial systems, these share the same physical characteristics viruses being anionic, nonaggregating, abundant, hollow, uniform in size, while effectively mediating gene silencing transgene expression. These are smallest structures reported to...
Despite continuing progress in kinesin enzyme mechanochemistry and emerging understanding of the cargo recognition machinery, it is not known how these functions are coupled controlled by α-helical coiled coils encoded a large component protein sequences. Here, we combine computational structure prediction with single-particle negative-stain electron microscopy to reveal coiled-coil architecture heterotetrameric kinesin-1 its compact state. An unusual flexion scaffold enables folding...
Correlative light-electron microscopy (CLEM) requires the availability of robust probes which are visible both in light and electron microscopy. Here we demonstrate a CLEM approach using small gold nanoparticles as single probe. Individual bound to epidermal growth factor protein were located with nanometric precision background-free human cancer cells by resonant four-wave mixing (FWM), correlatively mapped high accuracy corresponding transmission images. We used 10 nm 5 radius, show...
Abstract Many enzymes are allosterically regulated via conformational change; however, our ability to manipulate these structural changes and control function is limited. Here we install a switch for allosteric activation into the kinesin-1 microtubule motor in vitro cells. Kinesin-1 heterotetramer that accesses open active closed autoinhibited states. The equilibrium between states centers on flexible elbow within complex coiled-coil architecture. We target engineer state can be opened with...
An ability to organize and encapsulate multiple active proteins into defined objects spaces at the nanoscale has potential applications in biotechnology, nanotechnology, synthetic biology. Previously, we have described design, assembly, characterization of peptide-based self-assembled cages (SAGEs). These ≈100 nm particles comprise thousands copies de novo designed hubs that array a hexagonal network close give caged structures. Here, show that, when fused peptides, various natural can be...
Fluorescent nanodiamonds (fNDs) represent an emerging class of nanomaterials offering great opportunities for ultrahigh resolution imaging, sensing and drug delivery applications. Their biocompatibility, exceptional chemical consistent photostability renders them particularly attractive correlative light-electron microscopy studies providing unique insights into nanoparticle-cell interactions. Herein, we demonstrate a stringent procedure to image quantify fNDs with high contrast down the...
Abstract Bacterial microcompartments, BMCs, are proteinaceous organelles that encase a specific metabolic pathway within semi-permeable protein shell. Short encapsulation peptides can direct cargo proteins to the lumen of compartments. However, fusion such non-native does not guarantee and often causes aggregation. Here, we report an approach for targeting recombinant BMCs utilizes de novo coiled-coil protein–protein interactions. Attachment one module PduA (a component BMC shell) allows...
Microtubules and filamentous (F-) actin engage in complex interactions to drive many cellular processes from subcellular organization cell division migration. This is thought be largely controlled by proteins that interface between the two structurally distinct cytoskeletal components. Here, we use cryo-electron tomography demonstrate microtubule lumen can occupied extended segments of F-actin small molecule–induced, microtubule-based, projections. We uncover an unexpected versatility form...
To tackle the growing problem of antibiotic resistance, it is essential to identify new bioactive compounds that are effective against resistant microbes and safe use. Natural products their derivatives are, will continue be, an important source these molecules. Sea sponges harbour a diverse microbiome co-exists with sponge, bacterial communities produce rich array metabolites for protection resource competition. For reasons, sponge microbiota constitutes potential clinically relevant...
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...
ABSTRACT Complex machinery is required to drive secretory cargo export from the endoplasmic reticulum (ER), which an essential process in eukaryotic cells. In vertebrates, MIA3 gene encodes two major forms of transport and Golgi organization protein 1 (TANGO1S TANGO1L), have previously been implicated selective trafficking procollagen. Using genome engineering human cells, light microscopy, secretion assays, genomics proteomics, we show that disruption longer form, TANGO1L, results...
Please cite this paper as : Arkill KP, Neal CR, Mantell JM, Michel CC, Qvortrup K, Rostgaard J, Bates DO, Knupp C, Squire JM. 3D reconstruction of the glycocalyx structure in mammalian capillaries using electron tomography. Microcirculation 19: 343–351, 2012. Abstract Objective: Visualising molecular strands making up lumen small blood vessels has proved to be difficult conventional transmission microscopy techniques. Images obtained from tissue stained a variety ways have revealed...