Perez-Cobas A.E.,University of Valencia |
Gosalbes M.J.,University of Valencia |
Friedrichs A.,University of Kiel |
Knecht H.,University of Kiel |
And 18 more authors.
Gut | Year: 2013
Objective: Antibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy. Methods: The total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS2 instrument [UPLC-LTQ Orbitrap-MS/MS]) of a patient undergoing AB therapy for 14 days were evaluated. Results: Apparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by 'presumptive' naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while 'presumptively' attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host-microbial interactions significantly improved after treatment cessation. Conclusions: This proof-of-concept study provides an extensive description of gut microbiota responses to followup β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and diseases may alter gut microbial ecology and interactions with host metabolism at a much higher level than previously assumed.
Kubacka A.,CSIC - Institute of Catalysis |
Diez M.S.,Wageningen University |
Rojo D.,University of San Pablo - CEU |
Bargiela R.,CSIC - Institute of Catalysis |
And 8 more authors.
Scientific Reports | Year: 2014
Titania (TiO2)-based nanocomposites subjected to light excitation are remarkably effective in eliciting microbial death. However, the mechanism by which these materials induce microbial death and the effects that they have on microbes are poorly understood. Here, we assess the low dose radical-mediated TiO2 photocatalytic action of such nanocomposites and evaluate the genome/proteome-wide expression profiles of Pseudomonas aeruginosa PAO1 cells after two minutes of intervention. The results indicate that the impact on the gene-wide flux distribution and metabolism is moderate in the analysed time span. Rather, the photocatalytic action triggers the decreased expression of a large array of genes/proteins specific for regulatory, signalling and growth functions in parallel with subsequent selective effects on ion homeostasis, coenzyme-independent respiration and cell wall structure. The present work provides the first solid foundation for the biocidal action of titania and may have an impact on the design of highly active photobiocidal nanomaterials.
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.3.4-02 | Award Amount: 12.10M | Year: 2012
The 4-year SPLASH project will develop a new biobased industrial platform using microalgae as a renewable raw material for the sustainable production and recovery of hydrocarbons and (exo)polysaccharides from the species Botryococcus braunii and further conversion to renewable polymers. The project comprises 20 partners of which 40% SME and several large corporates plus universities and research institutes. Two bioproduction platforms will be explored: (1) green alga Botryococcus braunii on its own and (2) the green microalga Chlamydomonas reinhardtii, to which the unique hydrocarbon and polysaccharides producing genes from Botryococcus will be transferred. SPLASH will deliver knowledge, tools and technologies needed for the establishment of a new industry sector: Industrial Biotechnology with algae and/or algal genes for the manufacture of polyesters and polyolefins. The building blocks for these polymers will be derived from the sugars (polyesters) and hydrocarbons (polyolefins) exuded by the algae: adipic acid from galactose, 2,5-furandicarboxylic acid from glucose, rhamnose and fucose, 1,4-pentanediol from rhamnose and fucose, ethylene from green naphtha, propylene from green naphtha. The conversion of ethylene and propylene to polyolefins is common technology, and will not be included in the project. The sugar-derived building blocks will be converted to new condensation polymers, including poly(ethylene 2,5-furandioate) (PEF) and poly(1,4-pentylene adipate-co-2,5-furandioate). End-use applications include food packaging materials and fibres for yarns, ropes and nets. The project encompasses (1) development of Botryococcus as an industrial production platform, (2) Systems biology analysis, (3) Development of procedures for production, in situ extraction and isolation, (4) product development.
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.91M | Year: 2013
The PERFUME (PERoxisome Formation, Function, MEtabolism) program is an interdisciplinary and intersectoral ITN providing state-of-the-art research training at the interface of medicine, plant and fungal biology. The PERFUME S&T specifically aims at unraveling the principles of peroxisome biology. Peroxisomes have been discovered relatively recently (in 1954). Consequently, the level of understanding of their biology is relatively weak compared to the knowledge of other organelles. Despite their modest appearance, they are crucially important for cell vitality. Peroxisomes ubiquitously occur in eukaryotes, display an unprecedented versatility of functions and are essential in man. Recent findings indicate that improper functioning of peroxisomes contributes to ageing and age-related diseases. However, there are still major gaps in our current knowledge of peroxisome biology. PERFUME aims to fill these gaps by focusing on i) the identification of novel peroxisome functions, ii) in-depth understanding of the compartmentalization of functions in peroxisomes and iii) unraveling the principles of peroxisome proliferation. Enhancing knowledge on these three themes is relevant for medicine, agriculture and biotechnology and demands directed analyses, which require the combined expertise from different disciplines and sectors that cut across historically separated fields. PERFUME brings together such a team comprising of top scientists from the fields of cell biology, biochemistry, genomics, proteomics, metabolomics, mathematical modeling, bioinformatics and protein structure analysis. Together, PERFUME shows maximal complementarity and synergy to warrant optimal training facilities for the participating students.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.2-2 | Award Amount: 15.68M | Year: 2013
The overall goal with INFECT is to advance our understanding of the pathophysiological mechanisms, prognosis, and diagnosis of the multifactorial highly lethal NSTIs. The fulminant course of NSTIs (in the order of hours) demands immediate diagnosis and adequate interventions in order to salvage lives and limbs. However, diagnosis and management are difficult due to heterogeneity in clinical presentation, in co-morbidities and in microbiological aetiology. Thus, there is an urgent need for novel diagnostic and therapeutic strategies in order to improve outcome of NSTIs. To achieve this, a comprehensive and integrated knowledge of diagnostic features, causative microbial agent, treatment strategies, and pathogenic mechanisms (host and bacterial disease traits and their underlying interaction network) is required. INFECT is designed to obtain such insights through an integrated systems biology approach in patients and different clinically relevant experimental models. Specific objectives of INFECT are to: 1. Unravel specific mechanisms underlying diseases signatures though a bottom-up systems approach applied to clinically relevant experimental settings 2. Apply a top-down systems biology approach to NSTI patient samples to pin-point key host and pathogen factors involved in the onset and development of infection 3. Identify and quantify disease signatures and underlying networks that contribute to disease outcome 4. Exploit identified disease traits for the innovation of optimized diagnostic tools 5. Translate the advanced knowledge generated into evidence-based guidelines for classification and management, and novel therapeutic strategies We have gathered a team of multidisciplinary researchers, clinicians, SMEs and a patient organization, each with a unique expertise, technical platform and/or model systems that together provide the means to successfully conduct the multifaceted research proposed and efficiently disseminate/exploit the knowledge obtained.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.2-2 | Award Amount: 15.73M | Year: 2012
Inflammatory bowel disease (IBD) is a major health problem with severe co-morbidities, requiring life-long treatment. Oscillating processes, like biological clocks are well studied and modeled in a number of systems. Circadian rhythms are extremely important for optimal treatments of patients. Recently, the NfkB pathway has been shown to be oscillating. In this project, we will model NfkB oscillation in chronic inflammatory bowel diseases in animal models and patient cohorts with immunosuppressive treatments and controls. The aim is to build an experimentally validated model the NfkB oscillation in 4D within the gut tissue. Dynamic, experimental validation will be done for various types of cells in the gut by a combination of methods, including single-cell based transcriptomics, multi-photon microscopy and time-dependent, multi-component profiling. The validated model framework will enable searching for critical components of the NfB oscillation and to assess their relevance for the disease in patients. Interfering with the oscillation of biological pathways may provide new possibilities to influence biological processes like inflammation. Hence, we will search (assisted by the models and databases developed) for small molecules interfering with the NfkB oscillation in chemical databases and validate selected candidates in experimental systems. To this end, we will use cell lines with the correct indicator constructs using high content microscopy. To better translate the findings in animal models to patients, we will use a mouse model with transplanted human tissue so that we can verify the mathematical model in human tissue and verify functionality of small molecules in vivo. Owing to its systems, highly focused approach, the project will generate substantial insights into key mechanisms underlying IBD and will provide ways to modulate the oscillatory behavior of the NfB in IBD and IBD-dependent co-morbidities.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: BIOTEC-1-2014 | Award Amount: 6.84M | Year: 2015
We aim to engineer the lifestyle of Pseudomonas putida to generate a tailored, re-factored chassis with highly attractive new-to-nature properties, thereby opening the door to the production of thus far non-accessible compounds. This industrially driven project capitalises on the outstanding metabolic endowment and stress tolerance capabilities of this versatile bacterium for the production of specialty and bulk chemicals. Specifically, we will build streamlined P. putida strains with improved ATP availability utilizing this power on demand, decoupled from growth. The well-characterized, streamlined and re-factored strain platform will offer easy-to-use plug-in opportunities for novel, DNA-encoded functions under the control of orthogonal regulatory systems. To this end, we will deploy a concerted approach of genome refactoring, model-driven circuit design, implementation of ATP control loops, structured modelling and metabolic engineering. By drawing on a starkly improved, growth-uncoupled ATP-biosynthetic machinery, empowered P. putida strains will be able to produce a) n-butanol and isobutanol and their challenging gaseous derivatives 1-butene (BE) and (iso-)butadiene (BDE) using a novel, new-to-nature route starting from glucose, as well as b) new active ingredients for crop protection, such as tabtoxin, a high-value, -lactam-based secondary metabolite with a huge potential as a new herbicide. The game-changing innovations brought in in particular the uncoupling of ATP-synthesis and production from growth - will provide strong versatility, enhanced efficiency and efficacy to the production processes, thereby overcoming current bottlenecks, matching market needs and fostering high-level research growth and development.
De Rybel B.,Wageningen University |
Adibi M.,LifeGlimmer GmbH |
Adibi M.,Albert Ludwigs University of Freiburg |
Adibi M.,Wageningen University |
And 20 more authors.
Science | Year: 2014
Coordination of cell division and pattern formation is central to tissue and organ development, particularly in plants where walls prevent cell migration. Auxin and cytokinin are both critical for division and patterning, but it is unknown how these hormones converge upon tissue development. We identify a genetic network that reinforces an early embryonic bias in auxin distribution to create a local, nonresponding cytokinin source within the root vascular tissue. Experimental and theoretical evidence shows that these cells act as a tissue organizer by positioning the domain of oriented cell divisions. We further demonstrate that the auxin-cytokinin interaction acts as a spatial incoherent feed-forward loop, which is essential to generate distinct hormonal response zones, thus establishing a stable pattern within a growing vascular tissue.