Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Combined Transcriptome Sequencing of Mycoplasma hyopneumoniae and Infected Pig Lung Tissue Reveals Up-Regulation of Bacterial F1-Like ATPase and Down-Regulation of the P102 Cilium Adhesin in vivo
    Kamminga, Tjerko ; Benis, Nirupama ; Martins dos Santos, Vitor ; Bijlsma, Jetta J.E. ; Schaap, Peter J. - \ 2020
    Frontiers in Microbiology 11 (2020). - ISSN 1664-302X
    F1-like ATPase - host-pathogen interaction - infection - Mycoplasma hyopneumoniae - P102 cilium adhesin - pathogen enrichment - RNA sequencing

    Mycoplasma hyopneumoniae (M. hyopneumoniae) causes enzootic pneumonia in pigs but it is still largely unknown which host-pathogen interactions enable persistent infection and cause disease. In this study, we analyzed the host and bacterial transcriptomes during infection using RNA sequencing. Comparison of the transcriptome of lung lesion tissue from infected pigs with lung tissue from non-infected animals, identified 424 differentially expressed genes (FDR < 0.01 and fold change > 1.5LOG2). These genes were part of the following major pathways of the immune system: interleukin signaling (type 4, 10, 13, and 18), regulation of Toll-like receptors by endogenous ligand and activation of C3 and C5 in the complement system. Besides analyzing the lung transcriptome, a sampling protocol was developed to obtain enough bacterial mRNA from infected lung tissue for RNA sequencing. This was done by flushing infected lobes in the lung, and subsequently enriching for bacterial RNA. On average, 2.2 million bacterial reads were obtained per biological replicate to analyze the bacterial in vivo transcriptome. We compared the in vivo bacterial transcriptome with the transcriptome of bacteria grown in vitro and identified 22 up-regulated and 30 down-regulated genes (FDR < 0.01 and fold change > 2LOG2). Six out of seven genes in the operon encoding the mycoplasma specific F1-like ATPase (MHP_RS02445-MHP_RS02475) and all genes in the operon MHP_RS01965-MHP_RS01990 with functions related to nucleotide metabolism, spermidine transport and glycerol-3-phoshate transport were up-regulated in vivo. Down-regulated in vivo were genes related to glycerol uptake, cilium adhesion (P102), cell division and myo-inositol metabolism. In addition to providing a novel method to isolate bacterial mRNA from infected lung, this study provided insights into changes in gene expression during infection, which could help development of novel treatment strategies against enzootic pneumonia caused by M. hyopneumoniae.

    Rice seed sector development in the Ayeyarwady Delta : Review of lessons learned
    Gupta, Arnab ; Schaap, Mirjam ; Subedi, Abishkar - \ 2020
    Wageningen : Wageningen Centre for Development Innovation (Report / Wageningen Centre for Development Innovation WDCI-20-114) - 53
    Microbial hosts engineered for increased tolerance to temperature shifts
    Kampers, Linde Francisca Cornelia ; Volkers, Joanna Maria ; Schaap, Petrus Johannes ; Martins Dos Santos, Vitor Alexandre Pires - \ 2020
    Octrooinummer: WO2020094828, gepubliceerd: 2020-05-14.

    The present invention relates to microbial host cells that have been engineered for increased tolerance to temperature shifts, for increased performance at temperatures different from the microorganism's optimal temperature and/or for changing at least one of the microorganism's cardinal temperatures by replacing an endogenous NAD+ biosynthesis gene by a heterologous gene encoding a corresponding enzyme with another temperature profile and/or from a microorganism with a different optimum growth temperature.The invention further relates to processes wherein the engineered microbial host cells are used for producing a fermentation product,and to the use nucleotide sequences encoding NAD+ biosynthesis gene for changing at least one of a microorganism's cardinal temperatures and/or for improving a microorganism's tolerance to temperature shifts.

    MEMOTE for standardized genome-scale metabolic model testing
    Lieven, Christian ; Beber, Moritz E. ; Olivier, Brett G. ; Bergmann, Frank T. ; Ataman, Meric ; Babaei, Parizad ; Bartell, Jennifer A. ; Blank, Lars M. ; Chauhan, Siddharth ; Correia, Kevin ; Diener, Christian ; Dräger, Andreas ; Ebert, Birgitta E. ; Edirisinghe, Janaka N. ; Faria, José P. ; Feist, Adam M. ; Fengos, Georgios ; Fleming, Ronan M.T. ; García-Jiménez, Beatriz ; Hatzimanikatis, Vassily ; Helvoirt, Wout van; Henry, Christopher S. ; Hermjakob, Henning ; Herrgård, Markus J. ; Kaafarani, Ali ; Kim, Hyun Uk ; King, Zachary ; Klamt, Steffen ; Klipp, Edda ; Koehorst, Jasper J. ; König, Matthias ; Lakshmanan, Meiyappan ; Lee, Dong Yup ; Lee, Sang Yup ; Lee, Sunjae ; Lewis, Nathan E. ; Liu, Filipe ; Ma, Hongwu ; Machado, Daniel ; Mahadevan, Radhakrishnan ; Maia, Paulo ; Mardinoglu, Adil ; Medlock, Gregory L. ; Monk, Jonathan M. ; Nielsen, Jens ; Nielsen, Lars Keld ; Nogales, Juan ; Nookaew, Intawat ; Palsson, Bernhard O. ; Papin, Jason A. ; Patil, Kiran R. ; Poolman, Mark ; Price, Nathan D. ; Resendis-Antonio, Osbaldo ; Richelle, Anne ; Rocha, Isabel ; Sánchez, Benjamín J. ; Schaap, Peter J. ; Malik Sheriff, Rahuman S. ; Shoaie, Saeed ; Sonnenschein, Nikolaus ; Teusink, Bas ; Vilaça, Paulo ; Vik, Jon Olav ; Wodke, Judith A.H. ; Xavier, Joana C. ; Yuan, Qianqian ; Zakhartsev, Maksim ; Zhang, Cheng - \ 2020
    Nature Biotechnology 38 (2020)4. - ISSN 1087-0156 - 1 p.

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    Evaluation of diurnal responses of Tetradesmus obliquus under nitrogen limitation
    León-Saiki, G.M. ; Carreres, Benoit M. ; Remmers, Ilse M. ; Wijffels, René H. ; Martins dos Santos, Vitor A.P. ; Veen, Douwe van der; Schaap, Peter J. ; Suarez-Diez, Maria ; Martens, Dirk E. - \ 2020
    Algal Research 49 (2020). - ISSN 2211-9264
    Day/night cycles - Diurnal transcription changes - Microalgae - Nitrogen limitation - Scenedesmus obliquus - Starchless mutant

    Tetradesmus obliquus is an oleaginous microalga with high potential for triacylglycerol production. We characterized the biochemical composition and the transcriptional landscape of T. obliquus wild-type and the starchless mutant (slm1), adapted to 16:8 h light dark (LD) cycles under nitrogen limitation. In comparison to the nitrogen replete conditions, the diurnal RNA samples from both strains also displayed a cyclic pattern, but with much less variation which could be related to a reduced transcription activity in at least the usually highly active processes. During nitrogen limitation, the wild-type continued to use starch as the preferred storage compound to store energy and carbon. Starch was accumulated to an average content of 0.25 g·gDW −1, which is higher than the maximum observed under nitrogen replete conditions. Small oscillations were observed, indicating that starch was being used as a diurnal energy storage compound, but to a lesser extent than under nitrogen replete conditions. For the slm1 mutant, TAG content was higher than for the wild-type (average steady state value was 0.26 g·gDW −1 for slm1 compared to 0.06 g·gDW −1 for the wild-type). Despite the higher TAG content in the slm1, the conversion efficiency of photons into biomass components for the slm1 was only half of the one obtained for the wild-type. This is related to the observed decrease in biomass productivity (from 1.29 gDW·L−1·day−1 for the wild-type to 0.52 gDW·L−1·day−1 for the slm1). While the transcriptome of slm1 displayed clear signs of energy generation by degrading TAG and amino-acids during the dark period, no significant variation of these metabolites could be measured. When looking through the diurnal cycle, the photosynthetic efficiency was lower for the slm1 mutant compared to the wild-type especially during the second half of the light period, where starch accumulation occurred in the wild-type.

    Microbial lifestyle engineering
    Kampers, Linde F.C. - \ 2020
    Wageningen University. Promotor(en): V.A.P. Martins dos Santos, co-promotor(en): P.J. Schaap. - Wageningen : Wageningen University - ISBN 9789463953245 - 228

    Using Pseudomonas putida KT2440 as a proof-of-concept organism, this thesis was aimed at microbial lifestyle engineering for industrial applications. In this thesis, a structured approach was applied by first determining what microbial improvements industry is looking for by conducting a series of interviews with both industry and academia. Besides pinpointing the fields of interest from an industrial perspective, the interviews also clarified the limitations of the actual implementation of novel or (synthetically) adapted strains developed. Strain safety being at the top of their list, we first checked the claimed GRAS safety level of P. putida KT2440.

    A major obstacle for the breakthrough of P. putida KT2440 to be widely used as a biotechnological host is its obligate aerobic metabolism. In silico-directed strain improvement were initiated by the adaptation of strict aerobic P. putida KT2440 to micro-oxic and anoxic conditions. Adaptation to micro-oxic levels was done by first creating a design for a recombinant strain capable of anaerobic fermentation. The bottlenecks uncovered were resolved by insertion of three genes, and the recombinant strains were monitored through an adaptive laboratory evolution method with oxygen gradients set up specifically for this purpose. Recombinant strains were able to grow under micro-oxic conditions. Strain performance did not improve compared to the negative control under anoxic conditions. A more elaborate in-silico analysis was performed, combining protein domain analysis, transcriptomic analysis and genome-scale metabolic models to design a recombinant P. putida KT2440 strain capable of anaerobic respiration.

    Another general limitation in strains is their limited thermo-tolerance. We discovered a strong universal connection between NAD+ availability and thermo-tolerance. By replacing one single gene for a thermophilic heterolog in mesophilic prokaryotes, both P. putida and E. coli showed instant improved thermo-tolerance. Insertion of the aspartate NAD+ biogeneration pathway in eukaryotic yeast S. cerevisiae resulted in a similar effect. To determine the value of this thermo-tolerance in industry, a down-scaled microfluidics system was developed to mimic temperature fluctuations occurring in large scale  bioreactors. The novel discovery between thermo-tolerance and NAD+ availabilty was patented.

    MEMOTE for standardized genome-scale metabolic model testing
    Lieven, Christian ; Beber, Moritz E. ; Olivier, Brett G. ; Bergmann, Frank T. ; Ataman, Meric ; Babaei, Parizad ; Bartell, Jennifer A. ; Blank, Lars M. ; Chauhan, Siddharth ; Correia, Kevin ; Diener, Christian ; Dräger, Andreas ; Ebert, Birgitta E. ; Edirisinghe, Janaka N. ; Faria, José P. ; Feist, Adam M. ; Fengos, Georgios ; Fleming, Ronan M.T. ; García-Jiménez, Beatriz ; Hatzimanikatis, Vassily ; Helvoirt, Wout van; Henry, Christopher S. ; Hermjakob, Henning ; Herrgård, Markus J. ; Kaafarani, Ali ; Kim, Hyun Uk ; King, Zachary ; Klamt, Steffen ; Klipp, Edda ; Koehorst, Jasper J. ; König, Matthias ; Lakshmanan, Meiyappan ; Lee, Dong Yup ; Lee, Sang Yup ; Lee, Sunjae ; Lewis, Nathan E. ; Liu, Filipe ; Ma, Hongwu ; Machado, Daniel ; Mahadevan, Radhakrishnan ; Maia, Paulo ; Mardinoglu, Adil ; Medlock, Gregory L. ; Monk, Jonathan M. ; Nielsen, Jens ; Nielsen, Lars Keld ; Nogales, Juan ; Nookaew, Intawat ; Palsson, Bernhard O. ; Papin, Jason A. ; Patil, Kiran R. ; Poolman, Mark ; Price, Nathan D. ; Resendis-Antonio, Osbaldo ; Richelle, Anne ; Rocha, Isabel ; Sánchez, Benjamín J. ; Schaap, Peter J. ; Malik Sheriff, Rahuman S. ; Shoaie, Saeed ; Sonnenschein, Nikolaus ; Teusink, Bas ; Vilaça, Paulo ; Vik, Jon Olav ; Wodke, Judith A.H. ; Xavier, Joana C. ; Yuan, Qianqian ; Zakhartsev, Maksim ; Zhang, Cheng - \ 2020
    Nature Biotechnology 38 (2020)3. - ISSN 1087-0156 - p. 272 - 276.
    Toxicological response of the model fungus Saccharomyces cerevisiae to different concentrations of commercial graphene nanoplatelets
    Suarez-Diez, Maria ; Porras, Santiago ; Laguna-Teno, Felix ; Schaap, Peter J. ; Tamayo-Ramos, Juan A. - \ 2020
    Scientific Reports 10 (2020)1. - ISSN 2045-2322

    Graphene nanomaterials have attracted a great interest during the last years for different applications, but their possible impact on different biological systems remains unclear. Here, an assessment to understand the toxicity of commercial polycarboxylate functionalized graphene nanoplatelets (GN) on the unicellular fungal model Saccharomyces cerevisiae was performed. While cell proliferation was not negatively affected even in the presence of 800 mg L−1 of the nanomaterial for 24 hours, oxidative stress was induced at a lower concentration (160 mg L−1), after short exposure periods (2 and 4 hours). No DNA damage was observed under a comet assay analysis under the studied conditions. In addition, to pinpoint the molecular mechanisms behind the early oxidative damage induced by GN and to identify possible toxicity pathways, the transcriptome of S. cerevisiae exposed to 160 and 800 mg L−1 of GN was studied. Both GN concentrations induced expression changes in a common group of genes (337), many of them related to the fungal response to reduce the nanoparticles toxicity and to maintain cell homeostasis. Also, a high number of genes were only differentially expressed in the GN800 condition (3254), indicating that high GN concentrations can induce severe changes in the physiological state of the yeast.

    BENEFIT Partnership - 2019 annual report : Bilateral Ethiopian-Netherlands effort for food, income and trade partnership
    Alemu, Dawit ; Koomen, Irene ; Schaap, Mirjam ; Ayana, Amsalu ; Borman, Gareth ; Elias, Eyasu ; Smaling, Eric ; Getaw, Helen ; Becx, Gertjan ; Sopov, Monika ; Terefe, Geremew ; Schrader, Ted ; Tafere, Tewodros ; Vonk, Remko - \ 2020
    Wageningen : Wageningen Centre for Development Innovation (Report / Wageningen Centre for Development Innovation WCDI-20-094) - 211
    Klimaatadaptatie in de open teelten : Inventarisatie van klimaattrends, risico’s en adaptatiemaatregelen voor boerenbedrijven inde open teelten
    Verstand, Daan ; Schaap, Ben ; Schoorlemmer, Herman ; Wolf, Pieter de; Balen, Derk van; Verhagen, Jan - \ 2020
    Wageningen : Stichting Wageningen Research, Wageningen Plant Research (WPR), Businessunits Open Teelten en Agrosysteemkunde (Rapport / Stichting Wageningen Research, Wageningen Plant Research (WPR), Businessunits Open Teelten en Agrosysteemkunde WPR 824) - 89
    Effect of wheat bran derived prebiotic supplementation on gastrointestinal transit, gut microbiota, and metabolic health: a randomized controlled trial in healthy adults with a slow gut transit
    Müller, Mattea ; Hermes, Gerben D.A. ; Canfora, Emanuel E. ; Holst, Jens J. ; Zoetendal, Erwin G. ; Smidt, Hauke ; Troost, Freddy ; Schaap, Frank G. ; Damink, Steven Olde ; Jocken, Johan W.E. ; Lenaerts, Kaatje ; Masclee, Ad A.M. ; Blaak, Ellen E. - \ 2020
    Gut Microbes (2020). - ISSN 1949-0976
    Arabinoxylan-Oligosaccharides - Energy metabolism - Gastrointestinal transit - Gut Hormones - Gut microbiota - Prebiotic - Stool consistency

    Acute intake of the wheat bran extract Arabinoxylan-Oligosaccharide (AXOS) modulates the gut microbiota, improves stool characteristics and postprandial glycemia in healthy humans. Yet, little is known on how long-term AXOS intake influences gastrointestinal (GI) functioning, gut microbiota, and metabolic health. In this randomized, placebo-controlled, double-blind study, we evaluated the effects of AXOS intake on GI function and metabolic health in adults with slow GI transit without constipation. Forty-eight normoglycemic adults were included with whole-gut transit time (WGTT) of >35 h receiving either 15 g/day AXOS or placebo (maltodextrin) for 12-wks. The primary outcome was WGTT, and secondary outcomes included stool parameters, gut permeability, short-chain fatty acids (SCFA), microbiota composition, energy expenditure, substrate oxidation, glucose, insulin, lipids, gut hormones, and adipose tissue (AT) function. WGTT was unchanged, but stool consistency softened after AXOS. 12-wks of AXOS intake significantly changed the microbiota by increasing Bifidobacterium and decreasing microbial alpha-diversity. With a good classification accuracy, overall microbiota composition classified responders with decreased WGTT after AXOS. The incretin hormone Glucagon-like protein 1 was reduced after AXOS compared to placebo. Energy expenditure, plasma metabolites, AT parameters, SCFA, and gut permeability were unchanged. In conclusion, intake of wheat bran extract increases fecal Bifidobacterium and softens stool consistency without major effects on energy metabolism in healthy humans with a slow GI transit. We show that overall gut microbiota classified responders with decreased WGTT after AXOS highlighting that GI transit and change thereof were associated with gut microbiota independent of Bifidobacterium. NCT02491125.

    Time-dependent transcriptome profile of genes involved in triacylglycerol (TAG) and polyunsaturated fatty acid synthesis in Nannochloropsis gaditana during nitrogen starvation
    Janssen, Jorijn H. ; Spoelder, Jacco ; Koehorst, Jasper J. ; Schaap, Peter J. ; Wijffels, René H. ; Barbosa, Maria J. - \ 2020
    Journal of Applied Phycology 32 (2020). - ISSN 0921-8971 - p. 1153 - 1164.
    Microalgae - Nannochloropsis gaditana - Nitrogen starvation - Polyunsaturated fatty acids - Transcriptome - Triacylglycerol

    In this research, the gene expression of genes involved in lipid metabolism of the eustigmatophyte alga Nannochloropsis gaditana was measured by transcriptomic data. This microalga can be used as a source of triacylglycerol (TAG) and the omega-3 fatty acid eicosapentaenoic acid (EPA). Insight in TAG and EPA production and regulation are needed to improve their productivity. Nitrogen starvation induces TAG accumulation in N. gaditana. Previous research showed that during nitrogen starvation, EPA was translocated from the polar lipids to TAG and de novo synthesized in N. gaditana. Therefore, the expression levels of genes involved in fatty acid translocation and de novo TAG synthesis were measured. Furthermore, the genes involved in de novo EPA synthesis such as elongases and desaturases were studied. The expression levels were measured during the first hours of nitrogen starvation and the subsequent period of 14 days. One phospholipid:diacylglycerol acyltransferase (PDAT) gene involved in translocation of fatty acids from membrane lipids to TAG was upregulated. In addition, several lipases were upregulated, suggesting that these enzymes might be responsible for the translocation of EPA to TAG. Most desaturases and elongases involved in de novo EPA synthesis were downregulated during nitrogen starvation, except for Δ9 desaturase which was upregulated. This upregulation correlates with the increase in oleic acid. Due to the presence of many hypothetical genes, improvement in annotation is needed to increase our understanding of these pathways and their regulation.

    NG-Tax 2.0: A Semantic Framework for High-Throughput Amplicon Analysis
    Poncheewin, Wasin ; Hermes, Gerben D.A. ; Dam, Jesse C.J. Van; Koehorst, Jasper J. ; Smidt, Hauke ; Schaap, Peter J. - \ 2020
    Frontiers in Genetics Livestock Genomics 10 (2020). - ISSN 1664-8021
    NG-Tax 2.0 is a semantic framework for FAIR high-throughput analysis and classification of marker gene amplicon sequences including bacterial and archaeal 16S ribosomal RNA (rRNA), eukaryotic 18S rRNA and ribosomal intergenic transcribed spacer sequences. It can directly use single or merged reads, paired-end reads and unmerged paired-end reads from long range fragments as input to generate de novo amplicon sequence variants (ASV). Using the RDF data model, ASV’s can be automatically stored in a graph database as objects that link ASV sequences with the full data-wise and element-wise provenance, thereby achieving the level of interoperability required to utilize such data to its full potential. The graph database can be directly queried, allowing for comparative analyses of over thousands of samples and is connected with an interactive Rshiny toolbox for analysis and visualization of (meta) data. Additionally, NG-Tax 2.0 exports an extended BIOM 1.0 (JSON) file as starting point for further analyses by other means. The extended BIOM file contains new attribute types to include information about the command arguments used, the sequences of the ASVs formed, classification confidence scores and is backwards compatible. The performance of NG-Tax 2.0 was compared with DADA2, using the plugin in the QIIME 2 analysis pipeline. Fourteen 16S rRNA gene amplicon mock community samples were obtained from the literature and evaluated. Precision of NG-Tax 2.0 was significantly higher with an average of 0.95 vs 0.58 for QIIME2-DADA2 while recall was comparable with an average of 0.85 and 0.77, respectively. NG-Tax 2.0 is written in Java. The code, the ontology, a Galaxy platform implementation, the analysis toolbox, tutorials and example SPARQL queries are freely available at http://wurssb.gitlab.io/ngtax under the MIT License.
    Genome-guided analysis allows the identification of novel physiological traits in Trichococcus species
    Strepis, Nikolaos ; Naranjo, Henry D. ; Meier-Kolthoff, Jan ; Göker, Markus ; Shapiro, Nicole ; Kyrpides, Nikos ; Klenk, Hans Peter ; Schaap, Peter J. ; Stams, Alfons J.M. ; Sousa, Diana Z. - \ 2020
    BMC Genomics 21 (2020)1. - ISSN 1471-2164
    1,3-propanediol - Comparative genomics - Halophilic - Protein domains - Psychrophilic

    Background: The genus Trichococcus currently contains nine species: T. flocculiformis, T. pasteurii, T. palustris, T. collinsii, T. patagoniensis, T. ilyis, T. paludicola, T. alkaliphilus, and T. shcherbakoviae. In general, Trichococcus species can degrade a wide range of carbohydrates. However, only T. pasteurii and a non-characterized strain of Trichococcus, strain ES5, have the capacity of converting glycerol to mainly 1,3-propanediol. Comparative genomic analysis of Trichococcus species provides the opportunity to further explore the physiological potential and uncover novel properties of this genus. Results: In this study, a genotype-phenotype comparative analysis of Trichococcus strains was performed. The genome of Trichococcus strain ES5 was sequenced and included in the comparison with the other nine type strains. Genes encoding functions related to e.g. the utilization of different carbon sources (glycerol, arabinan and alginate), antibiotic resistance, tolerance to low temperature and osmoregulation could be identified in all the sequences analysed. T. pasteurii and Trichococcus strain ES5 contain a operon with genes encoding necessary enzymes for 1,3-PDO production from glycerol. All the analysed genomes comprise genes encoding for cold shock domains, but only five of the Trichococcus species can grow at 0 °C. Protein domains associated to osmoregulation mechanisms are encoded in the genomes of all Trichococcus species, except in T. palustris, which had a lower resistance to salinity than the other nine studied Trichococcus strains. Conclusions: Genome analysis and comparison of ten Trichococcus strains allowed the identification of physiological traits related to substrate utilization and environmental stress resistance (e.g. to cold and salinity). Some substrates were used by single species, e.g. alginate by T. collinsii and arabinan by T. alkaliphilus. Strain ES5 may represent a subspecies of Trichococcus flocculiformis and contrary to the type strain (DSM 2094T), is able to grow on glycerol with the production of 1,3-propanediol.

    Designing Eukaryotic Gene Expression Regulation Using Machine Learning
    Jongh, Ronald P.H. de; Dijk, Aalt D.J. van; Julsing, Mattijs K. ; Schaap, Peter J. ; Ridder, Dick de - \ 2020
    Trends in Biotechnology 38 (2020)2. - ISSN 0167-7799 - p. 191 - 201.
    DNA design - eukaryotic gene expression - gene regulation - machine learning - synthetic biology

    Controlling the expression of genes is one of the key challenges of synthetic biology. Until recently fine-tuned control has been out of reach, particularly in eukaryotes owing to their complexity of gene regulation. With advances in machine learning (ML) and in particular with increasing dataset sizes, models predicting gene expression levels from regulatory sequences can now be successfully constructed. Such models form the cornerstone of algorithms that allow users to design regulatory regions to achieve a specific gene expression level. In this review we discuss strategies for data collection, data encoding, ML practices, design algorithm choices, and finally model interpretation. Ultimately, these developments will provide synthetic biologists with highly specific genetic building blocks to rationally engineer complex pathways and circuits.

    Arabinoxylan-Oligosaccharide Intake changes the microbiota and softens stool consistency without changes in gut transit and metabolic health in healthy adults
    Müller, Mattea ; Hermes, Gerben ; Canfora, Emanuel E. ; Holst, Jens J. ; Zoetendal, Erwin ; Smidt, Hauke ; Troost, Freddy ; Schaap, Frank G. ; Damink, Steven Olde ; Jocken, Johan W.E. ; Lenaerts, Kaatje ; Masclee, Ad A.M. ; Blaak, Ellen E. - \ 2019
    Wageningen University & Research
    PRJEB32919 - ERP115659 - human gut metagenome
    Prebiotic fibers may alter gastrointestinal (GI) transit time, microbiota composition and short chain fatty acid (SCFA) production, contributing to improved gut functionality and metabolic health. We investigated long-term effects of Arabinoxylan-Oligosaccharide (AXOS), a prebiotic dietary fiber on GI transit time, gut microbiota composition, and metabolic profile in adult participants.Methods: This randomized, placebo-controlled double-blind parallel study included 48 normoglycemic men and women (ages 20-55 y, body mass index (BMI) 19.8-30.5 kg/m2) with a slow whole-gut transit time (>35h) recruited during August 2015 to December 2016 in Maastricht, the Netherlands. Participants were randomly allocated to 12 weeks 15g/day AXOS or placebo (maltodextrin) intake. GI transit time, stool parameters, gut permeability, SCFA and microbiota composition were assessed before and after. Energy expenditure, substrate oxidation, glucose, insulin, lipids and incretin hormones were measured during a breakfast meal test before and after.Results: AXOS significantly changed the microbiota (p=0.05) mainly by increasing Bifidobacterium and decreased microbial alpha-diversity (P<.001) as compared to placebo. Whole-gut and upper intestinal transit were not affected, but stool consistency softened after AXOS (Bristol stool chart score 2.7 ± 0.19 to 3.3 ± 0.19, P<.01). Postprandial fat oxidation tended to increase (iAUC, P=.073) and early GLP-1 response (AUC0-90min, P=.005) was reduced after AXOS. Energy expenditure, plasma metabolites, SCFA concentrations and gut permeability were unchanged. Microbiota could classify responders in improved whole-gut transit after AXOS with an ([ROC] AUC 0.80%).Conclusion: AXOS intake, changed the microbiota, mainly increased fecal Bifidobacterium, tended to increase postprandial fat oxidation and decreased the early GLP-1 response. Whilst we did not observe changes in whole-gut transit time, overall microbiota could accurately classify responders with improved GI transit after AXOS intake.
    Programmeringsstudie klimaatbestendig landelijk en stedelijk gebied : Programmeringsstudie voor de kennis- en innovatie agenda Landbouw, Water, Voedsel
    Hattum, Tim van; Hack, Mirjam ; Veraart, Jeroen ; Verhagen, Jan ; Schaap, Ben - \ 2019
    Wageningen : Wageningen Environmental Research (Rapport / Wageningen Environmental Research ) - 45
    Rubber van Paardenbloemen
    Meer, Ingrid van der - \ 2019
    Samenwerking voor een duurzame toekomst van het Nederlandse Zwartbles schaap
    Schoon, Mira - \ 2019
    Metabolic shift induced by synthetic co-cultivation promotes high yield of chain elongated acids from syngas
    Diender, Martijn ; Parera Olm, Ivette ; Gelderloos, Marten ; Koehorst, Jasper J. ; Schaap, Peter J. ; Stams, Alfons J.M. ; Sousa, Diana Z. - \ 2019
    Scientific Reports 9 (2019)1. - ISSN 2045-2322

    Bio-catalytic processes for sustainable production of chemicals and fuels receive increased attention within the concept of circular economy. Strategies to improve these production processes include genetic engineering of bio-catalysts or process technological optimization. Alternatively, synthetic microbial co-cultures can be used to enhance production of chemicals of interest. It remains often unclear however how microbe to microbe interactions affect the overall production process and how this can be further exploited for application. In the present study we explored the microbial interaction in a synthetic co-culture of Clostridium autoethanogenum and Clostridium kluyveri, producing chain elongated products from carbon monoxide. Monocultures of C. autoethanogenum converted CO to acetate and traces of ethanol, while during co-cultivation with C. kluyveri, it shifted its metabolism significantly towards solventogenesis. In C. autoethanogenum, expression of the genes involved in the central carbon- and energy-metabolism remained unchanged during co-cultivation compared to monoculture condition. Therefore the shift in the metabolic flux of C. autoethanogenum appears to be regulated by thermodynamics, and results from the continuous removal of ethanol by C. kluyveri. This trait could be further exploited, driving the metabolism of C. autoethanogenum to solely ethanol formation during co-cultivation, resulting in a high yield of chain elongated products from CO-derived electrons. This research highlights the important role of thermodynamic interactions in (synthetic) mixed microbial communities and shows that this can be exploited to promote desired conversions.

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