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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A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits
Snoek, B.L. ; Volkers, J.M. ; Nijveen, H. ; Petersen, Carola ; Dirksen, Philipp ; Sterken, M.G. ; Nakad, Rania ; Riksen, J.A.G. ; Rosenstiel, P.C. ; Stastna, J.J. ; Braekman, B.P. ; Harvey, S.C. ; Schulenburg, Hinrich ; Kammenga, J.E. - \ 2019
BMC Biology 17 (2019). - ISSN 1741-7007 - 17 p.
Background - The nematode Caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. Complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local C. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader scale.
Results - To investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11 kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping.
Conclusion -Taken together, we show that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates facilitates the detection of QTLs. The use of multi-parent RIL populations can further enhance our understanding of local adaptation and life history trade-offs.
Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1
Nakad, Rania ; Snoek, L.B. ; Yang, Wentao ; Ellendt, S. ; Schneider, Franziska ; Mohr, T.G. ; Rösingh, Lone ; Masche, Anna C. ; Rosenstiel, P.C. ; Dierking, K. ; Kammenga, J.E. ; Schulenburg, Hinrich - \ 2016
Caenorhabditis elegans - Pathogen avoidance behavior - Innate immunity - Immune specificity - QTL analyses
Background The invertebrate immune system comprises physiological mechanisms, physical barriers and also behavioral responses. It is generally related to the vertebrate innate immune system and widely believed to provide nonspecific defense against pathogens, whereby the response to different pathogen types is usually mediated by distinct signalling cascades. Recent work suggests that invertebrate immune defense can be more specific at least at the phenotypic level. The underlying genetic mechanisms are as yet poorly understood. Results We demonstrate in the model invertebrate Caenorhabditis elegans that a single gene, a homolog of the mammalian neuropeptide Y receptor gene, npr-1, mediates contrasting defense phenotypes towards two distinct pathogens, the Gram-positive Bacillus thuringiensis and the Gram-negative Pseudomonas aeruginosa. Our findings are based on combining quantitative trait loci (QTLs) analysis with functional genetic analysis and RNAseq-based transcriptomics. The QTL analysis focused on behavioral immune defense against B. thuringiensis, using recombinant inbred lines (RILs) and introgression lines (ILs). It revealed several defense QTLs, including one on chromosome X comprising the npr-1 gene. The wildtype N2 allele for the latter QTL was associated with reduced defense against B. thuringiensis and thus produced an opposite phenotype to that previously reported for the N2 npr-1 allele against P. aeruginosa. Analysis of npr-1 mutants confirmed these contrasting immune phenotypes for both avoidance behavior and nematode survival. Subsequent transcriptional profiling of C. elegans wildtype and npr-1 mutant suggested that npr-1 mediates defense against both pathogens through p38 MAPK signaling, insulin-like signaling, and C-type lectins. Importantly, increased defense towards P. aeruginosa seems to be additionally influenced through the induction of oxidative stress genes and activation of GATA transcription factors, while the repression of oxidative stress genes combined with activation of Ebox transcription factors appears to enhance susceptibility to B. thuringiensis. Conclusions Our findings highlight the role of a single gene, npr-1, in fine-tuning nematode immune defense, showing the ability of the invertebrate immune system to produce highly specialized and potentially opposing immune responses via single regulatory genes.
Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1
Nakad, Rania ; Snoek, Basten ; Yang, Wentao ; Ellendt, S. ; Schneider, Franziska ; Mohr, T.G. ; Rösingh, Lone ; Masche, Anna C. ; Rosenstiel, P.C. ; Dierking, K. ; Kammenga, Jan E. ; Schulenburg, Hinrich - \ 2016
BMC Genomics 17 (2016)1. - ISSN 1471-2164 - 20 p.
Background: The invertebrate immune system comprises physiological mechanisms, physical barriers and also behavioral responses. It is generally related to the vertebrate innate immune system and widely believed to provide
nonspecific defense against pathogens, whereby the response to different pathogen types is usually mediated by distinct signalling cascades. Recent work suggests that invertebrate immune defense can be more specific at least at
the phenotypic level. The underlying genetic mechanisms are as yet poorly understood. Results: We demonstrate in the model invertebrate Caenorhabditis elegans that a single gene, a homolog of the mammalian neuropeptide Y receptor gene, npr-1, mediates contrasting defense phenotypes towards two distinct pathogens, the Gram-positive Bacillus thuringiensis and the Gram-negative Pseudomonas aeruginosa. Our findings are based on combining quantitative trait loci (QTLs) analysis with functional genetic analysis and RNAseq-based transcriptomics. The QTL analysis focused on behavioral immune defense against B. thuringiensis, using recombinant inbred lines (RILs) and introgression lines (ILs). It revealed several defense QTLs, including one on chromosome X comprising the npr-1 gene. The wildtype N2 allele for the latter QTL was associated with reduced defense against B. thuringiensis and thus produced an opposite phenotype to that previously reported for the N2 npr-1 allele against P. aeruginosa. Analysis of npr-1 mutants confirmed these contrasting immune phenotypes for both avoidance behavior and nematode survival. Subsequent transcriptional profiling of C. elegans wildtype and npr-1 mutant suggested that npr-1 mediates defense against both pathogens through p38 MAPK signaling, insulin-like signaling, and C-type lectins. Importantly, increased defense towards P. aeruginosa seems to be additionally influenced through the induction of oxidative stress genes and activation of GATA transcription factors, while the repression of oxidative stress genes combined with activation of Ebox transcription factors appears to enhance susceptibility to B. thuringiensis. Conclusions: Our findings highlight the role of a single gene, npr-1, in fine-tuning nematode immune defense, showing the ability of the invertebrate immune system to produce highly specialized and potentially opposing immune responses via single regulatory genes.
Opposite immune responses in Caenorhabditis elegans caused by a single gene, the neuropeptide receptor gene npr-1
Nakad, R. ; Snoek, L.B. ; Yang, W. ; Dierking, K. ; Rosenstiel, P.C. ; Kammenga, J.E. ; Schulenburg, H. - \ 2015
In: Proceedings of the 20th International C. elegans Meeting. - Los Angeles, USA : - p. 62 - 62.
The nematode Caenorhabditis elegans feeds on microbes in its natural environment. Some of these microbes are pathogenic and thus harmful to the worm. To minimize fitness reductions, C. elegans has evolved various defence mechanisms including behavioural responses (i.e., avoidance behaviour). In this study, we characterized the genetic architecture of natural variation in C. elegans avoidance behaviour against the infectious stages of the Gram-positive bacterium Bacillus thuringiensis. We performed an analysis of quantitative trait loci (QTLs) using recombinant inbred lines (RILs) and introgression lines (ILs) generated from a cross of two genetically distinct C. elegans strains, N2 and CB4856. The analysis identified several QTLs that underlie variation in the behavioural response to pathogenic and non-pathogenic bacteria. One of the candidates is the npr-1 gene, which encodes a homolog of the mammalian neuropeptide receptor. Npr-1 was previously indicated to fully contribute to behavioural defence against the Gram-negative bacterium Pseudomonas aeruginosa. Surprisingly, npr-1 influences both survival and avoidance behaviour toward B. thuringiensis in exactly the opposite way than toward P. aeruginosa. We subsequently used RNA-Seq to explore in what way npr-1 differentially influences C. elegans defence responses toward these two distinct pathogen taxa. The analysis suggests that npr - 1 mediates resistance towards P. aeruginosa through the induction of oxidative stress genes and activation of GATA transcription factors, while it seems to contribute to susceptibility towards B. thuringiensis through the repression of oxidative stress genes combined with activation of Ebox transcription factors. Our findings highlight the role of npr-1 in fine-tuning nematode defence responses depending on the microbe to which C. elegans is exposed.
The mysterious role of the C.elegans nuclear hormone receptor NPR-1 in pathogen defense
Nakad, R. ; Snoek, L.B. ; Dierking, K. ; Yang, W. ; Kammenga, J.E. ; Schulenburg, H. - \ 2014
In: Proceedings of the Berlin C. elegans Meeting 2014. - - p. 194 - 194.
The nematode Caenorhabditis elegans feeds on microbes inits natural environment. Some of these microbes are pathogenic and thus harmful to C. elegans.Tominimize resulting fitness reductions,C. elegans has evolved various defence mechanisms including behavioural responses (e.g. avoidance behaviour) that reduce contact with the infectious microbes. In this study, we characterized the genetic architecture of natural variation in C. elegans avoidancebehaviour against the infectious stages of the Gram-positive bacterium Bacillus thuringiensis. We performed an analysis of quantitative trait loci (QTLs) using recombinant inbred lines (RILs) and introgression lines (ILs) generated from a cross of two genetically as well as phenotypically distinct natural isolates N2 and CB4856. The analysis identified several QTLs that underlie variation in the behavioural response to pathogenic and/or non-pathogenic bacteria. One of the candidates is the npr-1gene. This gene encodes a homolog of the mammalian neuropeptide receptor.Npr-1was previously indicated to fully contribute to behavioural defence against the Gram-negative bacterium Pseudomonas aeruginosa and food patch-leaving behaviour on Escherichia coli. Interestingly, inour study, npr-1is not the only gene mediating avoidance behaviour toward Bacillus thuringiensis. Moreover, our functional analyses show that npr-1alleles appear to influence survival and avoidance behaviour toward Bacillus thuringiensis inexactly the opposite way than toward Pseudomonas aeruginosa. Our findings highlight the role of npr-1infine-tuning nematode behaviourinan ecological context depending on the microbe to whichC. elegans is exposed.
Genetic architecture of natural variation in Caenorhabditis elegans pathogen avoidance
Nakad, R. ; Snoek, L.B. ; Ellendt, S. ; Mohr, T.G. ; Dierking, K. ; Kammenga, J.E. ; Schulenburg, J.H.G. van de - \ 2011
Genetic architecture of natural variation in caenorhabditis elegans pathogen avoidance
Nakad, R. ; Kammenga, J.E. ; Schulenburg, J.H.G. van de - \ 2010
In: Scientific Conference on Evolutionary Biology of Caenorhabditis and other Nematodes, Hinxton, Cambridge, UK, 5-8 June 2010. - - p. P35 - P35.
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