A5010812707- Microbial Metabolic Engineering and Bioproduction
- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Plant tissue culture and regeneration
- Gene Regulatory Network Analysis
- Plant Genetic and Mutation Studies
- Gut microbiota and health
- Biofuel production and bioconversion
- Pharmacogenetics and Drug Metabolism
- Parkinson's Disease Mechanisms and Treatments
- Transgenic Plants and Applications
- CRISPR and Genetic Engineering
- Computational Drug Discovery Methods
- Yeasts and Rust Fungi Studies
- RNA regulation and disease
- Neurological diseases and metabolism
- Plant Pathogens and Fungal Diseases
- Neurotransmitter Receptor Influence on Behavior
- Chromosomal and Genetic Variations
- Neurological disorders and treatments
- Seed Germination and Physiology
- Enzyme Catalysis and Immobilization
- Plant biochemistry and biosynthesis
- Potato Plant Research
- Plant Pathogens and Resistance
Leiden University
2019-2024
Centre for Human Drug Research
2019-2023
Netherlands Metabolomics Centre
2023
University of Luxembourg
2017-2019
Instituto de Genética Veterinaria
2012
A multitude of factors contribute to complex diseases and can be measured with 'omics' methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic Human (VMH, www.vmh.life) database encapsulating current knowledge human metabolism within five interlinked resources 'Human metabolism', 'Gut microbiome', 'Disease', 'Nutrition', 'ReconMaps'. The VMH captures 5180 unique metabolites, 17 730 reactions, 3695 genes, 255 Mendelian diseases, 818...
The human microbiome influences the efficacy and safety of a wide variety commonly prescribed drugs. Designing precision medicine approaches that incorporate microbial metabolism would require strain- molecule-resolved, scalable computational modeling. Here, we extend our previous resource genome-scale metabolic reconstructions gut microorganisms with greatly expanded version. AGORA2 (assembly organisms through reconstruction analysis, version 2) accounts for 7,302 strains, includes...
COnstraint-Based Reconstruction and Analysis (COBRA) provides a molecular mechanistic framework for integrative analysis of experimental data quantitative prediction physicochemically biochemically feasible phenotypic states. The COBRA Toolbox is comprehensive software suite interoperable methods. It has found widespread applications in biology, biomedicine, biotechnology because its functions can be flexibly combined to implement tailored protocols any biochemical network. Version 3.0...
The vast majority of Parkinson's disease cases are idiopathic. Unclear etiology and multifactorial nature complicate the comprehension pathogenesis. Identification early transcriptomic metabolic alterations consistent across different idiopathic (IPD) patients might reveal potential basis increased dopaminergic neuron vulnerability primary mechanisms. In this study, we combine systems biology data integration approaches to identify differences in signatures between IPD patient healthy...
The mechanism of each chemical reaction in a metabolic network can be represented as set atom mappings, which relates an substrate metabolite to the same element product metabolite. Genome-scale reconstructions typically represent biochemistry at level stoichiometry. However, more detailed representation underlying mappings opens possibility for broader range biological, biomedical and biotechnological applications than with stoichiometry alone. Complete manual acquisition mapping data...
Abstract The human microbiome influences the efficacy and safety of a wide variety commonly prescribed drugs, yet comprehensive systems-level approaches to interrogate drug-microbiome interactions are lacking. Here, we present computational resource microbial genome-scale reconstructions, deemed AGORA2, which accounts for 7,206 strains, includes drug degradation biotransformation, was extensively curated based on comparative genomics literature searches. AGORA2 serves as knowledge base...
The heterologous expression of isopentenyl transferase (IPT) under the transcriptional control senescence-associated receptor-like kinase (SARK) promoter delayed cellular senescence and, through it, increased drought tolerance in plants. To evaluate effect pSARK::IPT bread wheat, six independent transgenic events were obtained biolistic method and evaluated transgene expression, phenology, grain yield physiological biomass components plants grown both well-irrigating conditions. Experiments...
Two decades have passed since the first maize transformation protocol. Genetic breeding has been decisive and essential to transform a major food crop worldwide. Biotechnology plays an important role in plant genetic breeding, particularly for introduction of novel traits order improve agronomic performance, medical industrial applications quality. In recent years, development efficient regeneration systems cereal crops field biotechnology opened up new opportunities plants. Some monocot...
Somatic embryogenesis, which is still the method of choice for tissue culture, regeneration and transformation maize, largely considered highly genotype-dependent.The Hi II, a embryogenic genotype, has been extensively used in protocols.However, this not an inbred line; instead, it proportion undesirable A-188 background, progeny segregates phenotypic characteristics shows poor agronomic performance.In effort to identify genotypes that combine high somatic response good performance, we...
Abstract Starting with a comprehensive generic reconstruction of human metabolism, we generated high-quality, constraint-based, genome-scale, cell-type and condition specific models metabolism in dopaminergic neurons, the cell type most vulnerable to degeneration Parkinson ’ s disease. They are synthesis extensive manual curation biochemical literature on neuronal together novel, quantitative, transcriptomic targeted exometabolomic data from stem cell-derived, midbrainspecific, neurons vitro...
Abstract Constraint-based modelling can mechanistically simulate the behaviour of a biochemical system, permitting hypotheses generation, experimental design and interpretation data, with numerous applications, including metabolism. Given generic model, several methods have been developed to extract context-specific, genome-scale metabolic model by incorporating information used identify processes gene activities in given context. However, existing extraction algorithms are unable ensure...
Genome-scale metabolic reconstructions have been assembled for thousands of organisms using a wide range tools. However, metabolite annotations, required to compare and link metabolites between reconstructions, remain incomplete. Here, we aim further extend annotation coverage various databases chemoinformatic approaches.We developed COBRA toolbox extension, deemed MetaboAnnotator, which facilitates the comprehensive with database independent dependent identifiers, obtains molecular...
Abstract Certain neuronal populations are selectively vulnerable to alpha -synuclein pathology in Parkinson’s Disease, yet the reasons for this selectivity unclear. Pathology affects that anatomically connected although contribution of connectivity remains be quantitatively explored. Herein, we simulate connectome alone spread arbitrary aggregates using a computational model temporal within an abstract representation mouse mesoscale connectome. Our simulations compared with neuron-to-neuron...
Fluxomics seeks to infer reaction fluxes at genome-scale by introducing isotopically labelled metabolites into a living system and measuring the enrichment of isotopic tracers in downstream metabolites. This approach has potential quantify but current approaches steady-state metabolic are either not tractable or efficient as corresponding computational models high-dimensional, involve nonlinear constraints lack mathematical guarantees convergence global optimum. Herein, we introduce...
Quantitative inference of intracellular reaction rates is essential for characterising metabolic phenotypes. The classical experimental method measuring fluxes makes use stable-isotope tracing metabolites through the network, followed by mass spectrometry analysis. most common 13C-based flux analysis requires multidisciplinary knowledge in analytical chemistry, cell biology, and mathematical modelling, as well multiple independent tools handling data. Besides, usually carried out within a...
Maize (Zea mays) is a major food crop of the world. Biotechnology plays an important role in plant genetic improvement, particularly for introduction novel traits order to improve agronomic performance, medical and industrial applications quality. Particle bombardment rapid simple method that enables generation events affords genes expression studies. Nonetheless, appropriate reporter gene necessary visualize transformed cells. In this study, conditions transient maize calluses high low gun...