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Introduction
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Publications
Publications (69)
Effects on the growth and reproduction of birds are important endpoints in the environmental risk assessment (ERA) of pesticides. Toxicokinetic-toxicodynamic models based on dynamic energy budget theory (DEB) are promising tools to predict these effects mechanistically and make extrapolations relevant to ERA. However, before DEB-TKTD models are acc...
We present our work to develop a PBK model for fluopyram and its metabolite fluopyram-benzamide in male and female birds, for three bird species, chicken (Gallus gallus), duck (Mallard duck), and bobwhite quail (Colinus virginianus), based on a previously developed generic PBK model for the three bird species, to predict concentrations in tissues a...
The OSP Suite, including PK-Sim and MoBi, provides a powerful platform for PBK modeling and QSP modeling in simulating the behavior of environmental chemicals in animal species. The use of avian-specific PBK models can provide valuable information for ecotoxicological risk assessment, supplement the use of PBK models to answer specific risk assessm...
Birds build up their reproductive system and allocate substantial energy to egg-production for each reproductive season. Energetic specifics of these this processes are still not completely clear, despite the increasing interest. Environmental risk assessment (ERA) of commercial pesticides is currently based on the statistical analysis of data coll...
Mechanistic modeling of chronic chemical exposure in birds is gaining traction in environmental risk assessment. Such models provide insight into physiological effects and can predict life-history traits in response to exposure to chemical stress under laboratory or realistic field conditions.
Lately, the new guidance document on risk assessment fo...
Birds build up their reproductive system and undergo major tissue remodeling for each reproductive season. Energetic specifics of this process are still not completely clear, despite the increasing interest. We focused on the bobwhite quail-one of the most intensely studied species due to commercial and conservation interest-to elucidate the energy...
Physiologically-based kinetic (PBK) models are effective tools for designing toxicological studies and conducting extrapolations to inform hazard characterization in risk assessment by filling data gaps and defining safe levels of chemicals. In the present work, a generic avian PBK model for male and female birds was developed using PK-Sim and MoBi...
Welcome to our poster on how laying hen metabolism or residue studies can help assessing the suitability of Time Weighted Average (TWA) exposures in reproductive risk assessments for birds
We have developed this poster after the new draft EFSA Guidance for Bird and Mammal risk assessment stated that in future, the use of TWA for effects on chick de...
Physiologically based kinetic (PBK) models facilitate chemical risk assessment by predicting in vivo exposure while reducing the need for animal testing. PBK models for mammals have seen significant progress, which has yet to be achieved for avian systems. Here, we quantitatively compare physiological, metabolic and anatomical characteristics betwe...
Physiologically based kinetic (PBK) models are a promising tool for xenobiotic environmental risk assessment that could reduce animal testing by predicting in vivo exposure. PBK models for birds could further our understanding of species-specific sensitivities to xenobiotics, but would require species-specific parameterization. To this end, we summ...
The Michaelis constant KM describes the affinity of an enzyme for a specific substrate and is a central parameter in studies of enzyme kinetics and cellular physiology. As measurements of KM are often difficult and time-consuming, experimental estimates exist for only a minority of enzyme–substrate combinations even in model organisms. Here, we bui...
The regulation of resource allocation in biological systems observed today is the cumulative result of natural selection in ancestral and recent environments. To what extent are observed resource allocation patterns in different photosynthetic types optimally adapted to current conditions, and to what extent do they reflect ancestral environments?...
The availability of bacterial transcriptomes has dramatically increased in recent years. This data deluge could result in detailed inference of underlying regulatory networks, but the diversity of experimental platforms and protocols introduces critical biases that could hinder scalable analysis of existing data. Here, we show that the underlying s...
The Michaelis constant K M describes the affinity of an enzyme for a specific substrate, and is a central parameter in studies of enzyme kinetics and cellular physiology. As measurements of K M are often difficult and time-consuming, experimental estimates exist for only a minority of enzyme-substrate combinations even in model organisms. Here, we...
Significance
Enzyme kinetic parameters are crucial for a quantitative understanding of metabolism, but traditionally have to be measured in laborious low-throughput assays. To solve this problem, the enzyme turnover number, k cat , can be estimated in vivo, but it is unclear whether in vivo estimates represent stable systems parameters that can be...
Background:
Adaptive Laboratory Evolution (ALE) has emerged as an experimental approach to discover mutations that confer phenotypic functions of interest. However, the task of finding and understanding all beneficial mutations of an ALE experiment remains an open challenge for the field. To provide for better results than traditional methods of A...
Current machine learning classifiers have successfully been applied to whole-genome sequencing data to identify genetic determinants of antimicrobial resistance (AMR), but they lack causal interpretation. Here we present a metabolic model-based machine learning classifier, named Metabolic Allele Classifier (MAC), that uses flux balance analysis to...
Background:
The reconstruction of metabolic networks and the three-dimensional coverage of protein structures have reached the genome-scale in the widely studied Escherichia coli K-12 MG1655 strain. The combination of the two leads to the formation of a structural systems biology framework, which we have used to analyze differences between the rea...
The availability of gene expression data has dramatically increased in recent years. This data deluge could result in detailed inference of underlying regulatory networks, but the diversity of experimental platforms and protocols introduces critical biases that could hinder scalable analysis of existing data. Here, we show that the underlying struc...
Enzyme turnover numbers ( k cat s) are essential for a quantitative understanding of cells. Because k cat s are traditionally measured in low-throughput assays, they are often noisy, non-physiological, inconsistent, and labor-intensive to obtain.
We use a data-driven approach to estimate in vivo k cat s using metabolic specialist E. coli strains th...
Catalysis using iron–sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can prevent cell growth and survival when unmanaged, thus eliciting an essential stress response that is universal and fundamental in biology. Here we develop a co...
Systems biology describes cellular phenotypes as properties that emerge from the complex interactions of individual system components. Little is known about how these interactions have affected the evolution of metabolic enzymes. Here, we combine genome-scale metabolic modeling with population genetics models to simulate the evolution of enzyme tur...
Knowing the catalytic turnover numbers of enzymes is essential for understanding the growth rate, proteome composition, and physiology of organisms, but experimental data on enzyme turnover numbers is sparse and noisy. Here, we demonstrate that machine learning can successfully predict catalytic turnover numbers in Escherichia coli based on integra...
Mycobacterium tuberculosis is a serious human pathogen threat exhibiting complex evolution of antimicrobial resistance (AMR). Accordingly, the many publicly available datasets describing its AMR characteristics demand disparate data-type analyses. Here, we develop a reference strain-agnostic computational platform that uses machine learning approac...
- The regulation of resource allocation in biological systems observed today is the cumulative result of natural selection in ancestral and recent environments. To what extent are observed resource allocation patterns in different photosynthetic types optimally adapted to current conditions, and to what extend do they reflect ancestral environments...
Catalysis using iron-sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can completely inhibit cell growth when unmanaged and thus elicits an essential stress response that is universal and fundamental in biology. We develop a computab...
Systems biology describes cellular phenotypes as properties that emerge from the complex interactions of individual system components. Little is known about how these interactions have affected the evolution of metabolic enzymes. To address this question, we combine genome-scale metabolic modelling with population genetics models to simulate the ev...
HIGHLIGHTS The PRC2 interacting protein BLISTER likely acts downstream of PRC2 to silence Polycomb target genes and is a key regulator of specific stress responses in Arabidopsis.
Polycomb group (PcG) proteins are key epigenetic regulators of development. The highly conserved Polycomb repressive complex 2 (PRC2) represses thousands of target genes...
Harnessing natural variation in photosynthetic capacity is a promising route towards yield increases, but physiological phenotyping is still too laborious for large scale genetic screens. Here, we evaluate the potential of leaf reflectance spectroscopy to predict parameters of photosynthetic capacity in Brassica oleracea and Zea mays, a C3 and a C4...
To feed a world population projected to reach 9 billion people by 2050, the productivity of major crops must be increased by at least 50%. One potential route to boost the productivity of cereals is to equip them genetically with the ‘supercharged’ C4 type of photosynthesis; however, the necessary genetic modifications are not sufficiently understo...
C4 photosynthesis implements a biochemical carbon pump to suppress photorespiration. While this mechanism allows for increased photosynthetic efficiency, it requires the ancestral C3 state to be modified in terms of leaf anatomy, expression of metabolic genes, and enzyme kinetics. Despite the complexity of the C4 syndrome, it evolved in more than 6...
How did the complex metabolic systems we observe today evolve through adaptive evolution? The fitness landscape is the theoretical framework to answer this question. Since experimental data on natural fitness landscapes is scarce, computational models are a valuable tool to predict landscape topologies and evolutionary trajectories. Careful assumpt...
Transcript abundance of photorespiratory genes determined by read mapping on F. robusta full length transcript sequences.DOI:
http://dx.doi.org/10.7554/eLife.02478.008
Transcript abundance of C4 cycle genes determined by read mapping on F. robusta full length transcript sequences.DOI:
http://dx.doi.org/10.7554/eLife.02478.017
Quantitative information for all reads mapped in a cross species approach onto the reference transcriptome from Arabidopsis thaliana.DOI:
http://dx.doi.org/10.7554/eLife.02478.006
Fluxes over plasmodesmata depending on the weight on plasmodesmatal fluxes including flux variability analysis.DOI:
http://dx.doi.org/10.7554/eLife.02478.013
Fluxes over plasmodesmata depending on the weight on plasmodesmatal fluxes including flux variability analysis.DOI:
http://dx.doi.org/10.7554/eLife.02478.015
Quantification of C4 proteins by protein gel blots.DOI:
http://dx.doi.org/10.7554/eLife.02478.018
Results of the Illumina sequencing and cross species read mapping.DOI:
http://dx.doi.org/10.7554/eLife.02478.005
Quantification of photorespiratory proteins by protein gel blot.DOI:
http://dx.doi.org/10.7554/eLife.02478.009
C4 photosynthesis represents a most remarkable case of convergent evolution of a complex trait, which includes the reprogramming of the expression patterns of thousands of genes. Anatomical, physiological, and phylogenetic and analyses as well as computational modeling indicate that the establishment of a photorespiratory carbon pump (termed C2 pho...
An ultimate goal of evolutionary biology is the prediction and experimental verification of adaptive trajectories on macroevolutionary timescales. This aim has rarely been achieved for complex biological systems, as models usually lack clear correlates of organismal fitness. Here, we simulate the fitness landscape connecting two carbon fixation sys...
