Utrecht, Netherlands
Utrecht, Netherlands

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Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 2.85M | Year: 2016

MarPipe is a consortium of 11 partners (IBP-CNR, SZN, UiT, UNIABDN, GEOMAR, KULeuven, UCC, eCOAST, MEDINA, MicroDish, Italbiotec) based in 8 countries (I, N, UK, D, B, IRL, E, NL), including 3 from the non-academic sector. We will train 11 ESRs in marine drug-discovery, providing these researchers with unique skills toward becoming world leaders in this research field and to advance their careers in academia or industry. MarPipe PhDs will be trained in a programme including training-by-research, joint courses of technical, scientific and transferrable skills, active participation to public scientific events, and an intense inter-sectoral networking exchange plan. Marine organisms have the capacity to produce a variety of biologically potent natural products, including antibiotic and anticancer compounds. MarPipe aims at further development of antimicrobial and anticancer lead compounds originating from a previous EU project (PharmaSea), and will also explore the bioactivity of deep-sea samples (5000m) collected during the recent Eurofleet-2 project in the sub-Antarctic. The PhD students will thus be involved in all phases of the drug discovery pipeline, from isolation of new microbial strains to pre-clinical development of lead compounds. Importantly, they will also be trained to overcome existing bottlenecks in the field, e.g. low yields and low chemodiversity, isolation of known compounds, toxicity of compounds. The discovery rates of new bioactive antimicrobial and anticancer molecules will be enhanced through 11 PhD projects that cover all phases of the biodiscovery pipeline. As a final outcome of the project, we envisage the creation of a marine biodiscovery start-up company, which will include most of the MarPipe partners. The scientists of the future will be trained to become conscious about the socio-economic and policy context of their work, since several specific MarPipe PhD projects focus on legal, policy, innovation and entrepreneurship themes.

Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.3.2-02 | Award Amount: 11.97M | Year: 2012

Marine microorganisms form an almost untapped resource of biotechnological potential. However, its use is hindered by the low success rate of isolation of novel microorganisms and often by poor growth efficiency. Hence, the vast majority of marine microorganisms has not been cultivated and is often considered as unculturable. MaCuMBA aims at improving the isolation rate and growth efficiency of marine microorganisms from conventional and extreme habitats, by applying innovative methods, and the use of automated high throughput procedures. The approaches include the co-cultivation of interdependent microorganisms, as well as gradient cultures and other methods mimicking the natural environment, and the exploitation of cell-to-cell communication. Signaling molecules produced by microorganisms may be necessary for stimulating growth of the same or other species, or may prevent their growth. Signaling molecules also represent an interesting and marketable product. MaCuMBA will make use of high throughput platforms such Cocagne, using gel micro-droplet technology, or MicroDish in which many thousands of cultures are grown simultaneously. Various single-cell isolation methods, such as optical tweezers, will aid the isolation of specific target cells. Isolated microorganisms as well as their genomes will be screened for a wide range of bioactive products and other properties of biotechnological interest, such as genetic transformability. Growth efficiency and expression of silent genes of selected strains will be increased also by using the clues obtained from genomic information. MaCuMBA is targeted to SMEs and industry and they make a significant part of the consortium, ensuring that the project focuses on the interests of these partners. Moreover, MaCuMBA has adopted a comprehensive and professional exploitation, dissemination, implementation, and education strategy, ensuring that MaCuMBAs results and products will be directed to end-users and stakeholders.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.3.1-2 | Award Amount: 16.04M | Year: 2011

Antibiotics are essential therapeutics in the treatment of bacterial infections. However, the indiscriminate use of antibiotics has led to the emergence of antibiotic resistant bacteria that pose a major threat to human health as options for treating infections by these bacteria have become limited. The evolution, emergence and spread of antibiotic resistance genes are still only poorly understood and expanding our knowledge on these aspects will provide novel leads to combat the emergence of antibiotic resistance. The EvoTAR consortium gathers a multi-disciplinary group of leading European researchers in the fields of antibiotic resistance, microbial genomics and mathematical modelling. In addition, three research-intensive SMEs participate in EvoTAR, two of which are involved in the development of novel approaches to minimize the emergence and spread of antibiotic resistance. The purpose of EvoTAR is to increase the understanding of the evolution and spread of antibiotic resistance in human pathogens. EvoTAR will characterise the human reservoir of antibiotic resistance genes (the resistome) by investigating the dynamics and evolution of the interaction between resistant and non-resistant bacteria from the human microbiome and the interrelations of the human resistome with non-human reservoirs of resistance genes. Novel methods will be used to quantify resistance transfer under controlled conditions in gene exchange communities. Mathematical modelling will be applied to predict gene flow between different reservoirs and to predict future resistance trends. Novel in vitro and in vivo models will allow the study of the efficacy of novel therapeutics aimed at reducing selection and spread of antibiotic resistance. The EvoTAR project will generate novel insights into the evolution and spread of antibiotic resistance genes and thereby create opportunities for the development of novel interventions to curb the rising tide of antibiotic resistance in human pathogens.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE.2010.3.5-04 | Award Amount: 7.74M | Year: 2011

There is a strong need for new thermostable hydrolases with appropriate performance and/or novel functionalities that could provide huge savings in time, money and energy for industrial processes. The HotZyme project aims to identify such enzymes from hot terrestial environments, using metagenomic screening methods. New bioinfomatic tools will be developed to facilitate function prediction of genes from metagenomes that show low or no sequence homology to enzymes of known function. A range of high-throughput screening technologies will be employed to identify novel hydrolases. The consortium is composed of 13 partners from 10 European countries plus one partner from USA. The strong expertise in Microbiology, Moleculary Biology, Biochemistry, Biophysics, Geochemistry, Nanotechnology and Bioinformatics from our partners will be integrated in the project to ensure the fulfilment of the proposed tasks. Importantly, the five industrial partners, including three SMEs, will seek to commercialize the project results, thus ensuring a European wide impact, post project.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: KBBE-2009-3-6-03 | Award Amount: 3.91M | Year: 2010

BIOMONAR develops multiplexed nanoarray biosensors for environmental targets, i.e. pollutants and pathogens. The innovative approach engineers three sensor platforms (surface, liposomal, living cell) which exploit a panel of periplasmic binding proteins (PBPs) as the common selective element. The nanoarrays are integrated into a microfluidics system for in-situ monitoring. The strategy allows for selective and sensitive detection of target compounds in complex environmental mixtures. The sensor platforms probe different aspects in the exposure to effect chain of processes: each responds to a certain proportion of the total target concentration and has a characteristic dynamic window. The sensor signals are quantitatively interpreted and represented in terms of the spectra of reactivities and fluxes of the target compounds. This level of sophistication, coupled with the common PBP selective component, allows a coherent elucidation of the link between dynamic target speciation and predicted ecotoxicological impact. The optimisation and dedication of the sensors for environmental monitoring inherently involves physicochemical characterisation of the various bio/nonbio and bio/bio interfacial processes at nanoscale. The ensuing knowledge on the interaction of nanostructured surfaces with biological systems facilitates design of sensors for new targets, thus providing technical opportunities for the biosensor industry.

Szabo Z.,MicroDish BV | Pohlschroder M.,University of Pennsylvania
Frontiers in Microbiology | Year: 2012

Secreted proteins make up a significant percentage of a prokaryotic proteome and play critical roles in important cellular processes such as polymer degradation, nutrient uptake, signal transduction, cell wall biosynthesis, and motility.The majority of archaeal proteins are believed to be secreted either in an unfolded conformation via the universally conserved Sec pathway or in a folded conformation via theTwin arginine transport (Tat) pathway. Extensive in vivo and in silico analyses of N-terminal signal peptides that target proteins to these pathways have led to the development of computational tools that not only predict Sec and Tat substrates with high accuracy but also provide information about signal peptide processing and targeting. Predictions therefore include indications as to whether a substrate is a soluble secreted protein, a membrane or cell wall anchored protein, or a surface structure subunit, and whether it is targeted for post-translational modification such as glycosylation or the addition of a lipid. The use of these in silico tools, in combination with biochemical and genetic analyses of transport pathways and their substrates, has resulted in improved predictions of the subcellular localization of archaeal secreted proteins, allowing for a more accurate annotation of archaeal proteomes, and has led to the identification of potential adaptations to extreme environments, as well as phyla-specific pathways among the archaea. A more comprehensive understanding of the transport pathways used and post-translational modifications of secreted archaeal proteins will also facilitate the identification and heterologous expression of commercially valuable archaeal enzymes. © 2012 Szabo and Pohlschroder.

Ariel G.,Bar - Ilan University | Shklarsh A.,Tel Aviv University | Kalisman O.,Tel Aviv University | Ingham C.,Microdish BV | And 2 more authors.
New Journal of Physics | Year: 2013

Bacterial swarming resulting in collective navigation over surfaces provides a valuable example of cooperative colonization of new territories. The social bacterium Paenibacillus vortex exhibits successful and diverse swarming strategies. When grown on hard agar surfaces with peptone, P. vortex develops complex colonies of vortices (rotating bacterial aggregates). In contrast, during growth on Mueller-Hinton broth gelled into a soft agar surface, a new strategy of multi-level organization is revealed: the colonies are organized into a special network of swarms (or 'snakes' of a fraction of millimeter in width) with intricate internal traffic. More specifically, cell movement is organized in two or three lanes of bacteria traveling between the back and the front of the swarm. This special form of cellular logistics suggests new methods in which bacteria can share resources and risk while searching for food or migrating into new territories. While the vortices-based organization on hard agar surfaces has been modeled before, here, we introduce a new multi-agent bacterial swarming model devised to capture the swarms-based organization on soft surfaces. We test two putative generic mechanisms that may underlie the observed swarming logistics: (i) chemo-activated taxis in response to chemical cues and (ii) special align-and-push interactions between the bacteria and the boundary of the layer of lubricant collectively generated by the swarming bacteria. Using realistic parameters, the model captures the observed phenomena with semi-quantitative agreement in terms of the velocity as well as the dynamics of the swarm and its envelope. This agreement implies that the bacteria interactions with the swarm boundary play a crucial role in mediating the interplay between the collective movement of the swarm and the internal traffic dynamics. © IOP Publishing and Deutsche Physikalische Gesellschaft.

den Hertog A.L.,Royal Tropical Institute | Ingham C.J.,Microdish BV | Fey F.H.A.G.,Center for Concepts in Mechatronics | Klatser P.R.,Royal Tropical Institute | Anthony R.M.,Royal Tropical Institute
PLoS ONE | Year: 2010

Background Even with the advent of nucleic acid (NA) amplification technologies the culture of mycobacteria for diagnostic and other applications remains of critical importance. Notably microscopic observed drug susceptibility testing (MODS), as opposed to traditional culture on solid media or automated liquid culture, has shown potential to both speed up and increase the provision of mycobacterial culture in high burden settings. Methods Here we explore the growth of Mycobacterial tuberculosis microcolonies, imaged by automated digital microscopy, cultured on a porous aluminium oxide (PAO) supports. Repeated imaging during colony growth greatly simplifies "computer vision" and presumptive identification of microcolonies was achieved here using existing publically available algorithms. Our system thus allows the growth of individual microcolonies to be monitored and critically, also to change the media during the growth phase without disrupting the microcolonies. Transfer of identified microcolonies onto selective media allowed us, within 1-2 bacterial generations, to rapidly detect the drug susceptibility of individual microcolonies, eliminating the need for time consuming subculturing or the inoculation of multiple parallel cultures. Significance Monitoring the phenotype of individual microcolonies as they grow has immense potential for research, screening, and ultimately M. tuberculosis diagnostic applications. The method described is particularly appealing with respect to speed and automation. © 2010 den Hertog et al.

Ingham C.J.,MicroDish BV | Ingham C.J.,Wageningen University | ter Maat J.,MicroDish BV | ter Maat J.,Wageningen University | de Vos W.M.,Wageningen University
Biotechnology Advances | Year: 2012

Porous aluminum oxide (PAO) is a ceramic formed by an anodization process of pure aluminum that enables the controllable assembly of exceptionally dense and regular nanopores in a planar membrane. As a consequence, PAO has a high porosity, nanopores with high aspect ratio, biocompatibility and the potential for high sensitivity imaging and diverse surface modifications. These properties have made this unusual material attractive to a disparate set of applications. This review examines how the structure and properties of PAO connect with its present and potential uses within research and biotechnology. The role of PAO is covered in areas including microbiology, mammalian cell culture, sensitive detection methods, microarrays and other molecular assays, and in creating new nanostructures with further uses within biology. © 2011 Elsevier Inc.

Ingham C.J.,Robert Bosch GmbH | Ingham C.J.,Wageningen University | Ingham C.J.,MicroDish BV | Schneeberger P.M.,Robert Bosch GmbH
PLoS ONE | Year: 2012

Background: The echinocandins are lipopeptides that can be employed as antifungal drugs that inhibit the synthesis of 1,3-β-glucans within the fungal cell wall. Anidulafungin and caspofungin are echinocandins used in the treatment of Candida infections and have activity against other fungi including Aspergillus fumigatus. The echinocandins are generally considered fungistatic against Aspergillus species. Methods: Culture of A. fumigatus from conidia to microcolonies on a support of porous aluminium oxide (PAO), combined with fluorescence microscopy and scanning electron microscopy, was used to investigate the effects of anidulafungin and caspofungin. The PAO was an effective matrix for conidial germination and microcolony growth. Additionally, PAO supports could be moved between agar plates containing different concentrations of echinocandins to change dosage and to investigate the recovery of fungal microcolonies from these drugs. Culture on PAO combined with microscopy and image analysis permits quantitative studies on microcolony growth with the flexibility of adding or removing antifungal agents, dyes, fixatives or osmotic stresses during growth with minimal disturbance of fungal microcolonies. Significance: Anidulafungin and caspofungin reduced but did not halt growth at the microcony level; additionally both drugs killed individual cells, particularly at concentrations around the MIC. Intact but not lysed cells showed rapid recovery when the drugs were removed. The classification of these drugs as either fungistatic or fungicidal is simplistic. Microcolony analysis on PAO appears to be a valuable tool to investigate the action of antifungal agents. © 2012 Ingham, Schneeberger.

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