Discovery pipelines for marine resources : an ocean of opportunity for biotechnology?

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 645884. CABI is an international intergovernmental organisation, and we gratefully acknowledge the core financial support from our member countries (and lead agencies) including the United Kingdom (Department for International Development), China (Chinese Ministry of Agriculture), Australia (Australian Centre for International Agricultural Research), Canada (Agriculture and Agri-Food Canada), Netherlands (Directorate-General for International Cooperation),and Switzerland (Swiss Agency for Development and Cooperation). See https://www.cabi.org/about-cabi/who-we-work-with/key-donors/ for full details.Marine microbial diversity offers enormous potential for discovery of compounds of crucial importance in healthcare, food security and bioindustry. However, access to it has been hampered by the difficulty of accessing and growing the organisms for study. The discovery and exploitation of marine bioproducts for research and commercial development requires state-of-the-art technologies and innovative approaches. Technologies and approaches are advancing rapidly and keeping pace is expensive and time consuming. There is a pressing need for clear guidance that will allow researchers to operate in a way that enables the optimal return on their efforts whilst being fully compliant with the current regulatory framework. One major initiative launched to achieve this, has been the advent of European Research Infrastructures. Research Infrastructures (RI) and associated centres of excellence currently build harmonized multidisciplinary workflows that support academic and private sector users. The European Marine Biological Research Infrastructure Cluster (EMBRIC) has brought together six such RIs in a European project to promote the blue bio-economy. The overarching objective is to develop coherent chains of high-quality services for access to biological, analytical and data resources providing improvements in the throughput and efficiency of workflows for discovery of novel marine products. In order to test the efficiency of this prototype pipeline for discovery, 248 rarely-grown organisms were isolated and analysed, some extracts demonstrated interesting biochemical properties and are currently undergoing further analysis. EMBRIC has established an overarching and operational structure to facilitate the integration of the multidisciplinary value chains of services to access such resources whilst enabling critical mass to focus on problem resolution.Publisher PDFPeer reviewe

In Vitro Model of the Gram-Negative Bacterial Cell Envelope for Investigation of Anti-Infective Permeation Kinetics

The cell envelope of Gram-negative bacteria is a formidable biological barrier, inhibiting the action of antibiotics by impeding their permeation into the intracellular environment. In-depth understanding of permeation through this barrier remains a challenge, despite its critical role in antibiotic activity. We therefore designed a divisible in vitro permeation model of the Gram-negative bacterial cell envelope, mimicking its three essential structural elements, the inner membrane and the periplasmic space as well as the outer membrane, on a Transwell setup. The model was characterized by contemporary imaging techniques and employed to generate reproducible quantitative and time-resolved permeation data for various fluorescent probes and anti-infective molecules of different structure and physicochemical properties. For a set of three fluorescent probes, the permeation through the overall membrane model was found to correlate with in bacterio permeation. Even more interestingly, for a set of six Pseudomonas quorum sensing inhibitors, such permeability data were found to be predictive for their corresponding in bacterio activities. Further exploration of the capabilities of the overall model yielded a correlation between the permeability of porin-independent antibiotics and published in bacterio accumulation data; a promising ability to provide structure-permeability information was also demonstrated. Such a model may therefore constitute a valuable tool for the development of novel anti-infective drugs

Heterojunction based hybrid silicon nanowire solar cell: surface termination, photoelectron and photoemission spectroscopy study

Silicon nanowires (SiNWs) combined with a conducting polymer are studied to constitute a hybrid organic/inorganic solar cell. This type of cell shows a particularly high interfacial area between SiNWs and the polymer so that interfacial control and interface optimization are required. For that purpose, we terminated the SiNW surfaces with well selected functional groups (molecules) such as native oxide (hereinafter SiO2-SiNW), hydrogen (hereinafter H-SiNW) and methyl (hereinafter CH3-SiNW). A radial hetero-junction solar cell is formed, and the cell parameters with and without interface control by functionalization with molecules are compared. Electronically, the three surfaces were close to flat-band conditions. The CH3-SiNW, H-SiNW and SiO2-SiNW produced a surface dipole of -0.12, +0.07 and 0.2eV and band bending of 50, 100 and 170meV, respectively. The surface properties of functionalized SiNWs are investigated by photoelectron yield (PY) and photoemission spectroscopy. PY studies on functionalized SiNWs are presented for the first time, and our results show that this type of measurement is an excellent option to carry out interface optimization of NWs for envisaged nano-electronic and photonic applications. The solar cell efficiency is increased dramatically after terminating the surface with CH3 molecules due to the decrease of the defect emission. The differently functionalized SiNW surfaces showed identical absorbance, reflectance and transmission so that a change in PY can be attributed to the Si-C bonds at the surface. This finding permits the design of new solar cell concepts. Copyright (c) 2013 John Wiley & Sons, Ltd

Improving the properties of ceramic foams by a vacuum infiltration process

Reticulated ceramic foams are widely used for industrial applications such as metal filtration, exhaust gas and air purification, catalyst support and others. In this work, the compression strength and specific surface area of reticulated foams have been improved, while at the same time maintaining a high level of permeability in the final foam structure. In particular, a vacuum infiltration step by using a suitable slurry, followed by a pre-sintering cycle was adopted for filling up the hollow struts, generated due to the burnout of the PU foam. Furthermore, various mixtures of fine and coarse-grained alumina as well as in combination with zirconia, were utilised with the aim of controlling the foam properties such as compression strength, specific surface area and permeability. The compression strength was improved by a factor of two for alumina foams by infiltrating the hollow struts, and by a factor of four when infiltrating the struts of ZTA foams, with the composition 70 mol% Al2O3 and 30 mol% ZrO2. The weight gain resulting from the vacuum infiltration process was in the order of 10 wt%

Realization of Vertical and Zigzag Single Crystalline Silicon Nanowire Architectures

Silicon nanowire (SiNW) ensembles, with vertical and zigzag architectures have been realized using wet chemical etching of bulk silicon wafers (p-Si(l 11) and p-Si(100)) with it mask of silver nanoparticles that are deposited by wet electroless deposition. The etching of SiNWs is based oil Subsequent treatments in chemical Solutions Such is 0.02 M aqueous Solutions of silver nitrate (AgNO(3)) followed by 5 M hydrofluoric acid and 30% hydrogen peroxide (H(2)O(2)). The etching of the Si wafers is mediated by the reduction of silver oil the Silicon Surface and in parallel by the oxidation of Si thereby forming SiO(2) which is dissolved ill the HF Surroundings. The morphology of the starting silver (Ag) layer/Ag nanoparticles that form during processing oil the Si wafer surfaces strongly influences the morphology of the SiNW ensembles and homogeneity of the etch profile. Our observations Suggest that the Ag layer/Ag nanoparticles not only catalyze the wet chemical etching of silicon but also strongly catalyze the decomposition of H(2)O(2) so that the temperature of the etching Solution substantially increases (strong exothermic reaction) and thus the etching velocity of bulk material. The morphology and microstructure of single crystalline SiNWs with respect to their crystallographic orientation was investigated by scanning (SEM) and transmission electron (TEM) microscopies and by electron backscatter diffraction (EBSD) in ill SEM. Straight SiNWs Lis well as zigzag SiNWs can be realized depending oil processing peculiarities. The optical characteristics such as absorption, transmission, and reflectance of the different silicon 1D architectures were investigated in an integrating sphere. Strong absorption and less reflection of visible and near-infrared light by the SiNW ensembles Suggest that Such material call he applied in the fields of opto-electronics, photonics and photovoltaics

Applying contact to individual silicon nanowires using a dielectrophoresis (DEP)-based technique

One major challenge for the technological use of nanostructures is the control of their electrical and optoelectronic properties. For that purpose, extensive research into the electrical characterization and therefore a fast and reliable way of contacting these structures are needed. Here, we report on a new, dielectrophoresis (DEP)-based technique, which enables to apply sufficient and reliable contact to individual nanostructures, like semiconducting nanowires (NW), easily and without the need for lithography. The DEP contacting technique presented in this article can be done without high-tech equipment and monitored in situ with an optical microscope. In the presented experiments, individual SiNWs are trapped and subsequently welded between two photolithographically pre-patterned electrodes by applying varying AC voltages to the electrodes. To proof the quality of these contacts, I-V curves, photoresponse and photoconductivity of a single SiNW were measured. Furthermore, the measured photoconductivity in dependence on the wavelength of illuminated light and was compared with calculations predicting the absorption spectra of an individual SiNW

Adaptation of a Bacterial Multidrug Resistance System Revealed by the Structure and Function of {AlbA}

To combat the rise of antimicrobial resistance, the discovery of new antibiotics is paramount. Albicidin and cystobactamid are related natural product antibiotics with potent activity against Gram-positive and, crucially, Gram-negative pathogens. AlbA has been reported to neutralize albicidin by binding it with nanomolar affinity. To understand this potential resistance mechanism, we determined structures of AlbA and its complex with albicidin. The structures revealed AlbA to be comprised of two domains, each unexpectedly resembling the multiantibiotic neutralizing protein TipA. Binding of the long albicidin molecule was shared pseudosymmetrically between the two domains. The structure also revealed an unexpected chemical modification of albicidin, which we demonstrate to be promoted by AlbA, and to reduce albicidin potency; we propose a mechanism for this reaction. Overall, our findings suggest that AlbA arose through internal duplication in an ancient TipA-like gene, leading to a new binding scaffold adapted to the sequestration of long-chain antibiotics

Targeting DnaN for tuberculosis therapy using novel griselimycins

The discovery of Streptomyces-produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant Mycobacterium tuberculosis has prioritized the need for new drugs. Here we show that new optimized derivatives from Streptomyces-derived griselimycin are highly active against M. tuberculosis, both in vitro and in vivo, by inhibiting the DNA polymerase sliding clamp DnaN. We discovered that resistance to griselimycins, occurring at very low frequency, is associated with amplification of a chromosomal segment containing dnaN, as well as the ori site. Our results demonstrate that griselimycins have high translational potential for tuberculosis treatment, validate DnaN as an antimicrobial target, and capture the process of antibiotic pressure-induced gene amplification