A5069362994- Microbial Metabolic Engineering and Bioproduction
- Bioinformatics and Genomic Networks
- Gene Regulatory Network Analysis
- Metabolomics and Mass Spectrometry Studies
- Gut microbiota and health
- Biofuel production and bioconversion
- Protein Structure and Dynamics
- Parkinson's Disease Mechanisms and Treatments
- Diet and metabolism studies
- Advanced Optimization Algorithms Research
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Genomics and Phylogenetic Studies
- Enzyme Catalysis and Immobilization
- Neuroscience and Neural Engineering
- RNA and protein synthesis mechanisms
- Optimization and Variational Analysis
- Process Optimization and Integration
- Pharmacogenetics and Drug Metabolism
- Tryptophan and brain disorders
- Bacterial Genetics and Biotechnology
- Microfluidic and Bio-sensing Technologies
- Crystallization and Solubility Studies
- thermodynamics and calorimetric analyses
- Drug Transport and Resistance Mechanisms
Ollscoil na Gaillimhe – University of Galway
2007-2025
Leiden University
2018-2024
Centre for Human Drug Research
2018-2024
University of Luxembourg
2013-2023
National University of Ireland
2021-2023
Medical University of Vienna
2020
Netherlands Metabolomics Centre
2019
University of Iceland
2009-2014
Faculty (United Kingdom)
2013
Center for Systems Biology
2013
Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate complexity brain. Here, we describe a robust organoid system highly specific to midbrain derived from regionally patterned neuroepithelial stem cells. These organoids contain spatially organized groups dopaminergic neurons, which make them an attractive model for study Parkinson's disease. Midbrain are characterized detail neuronal, astroglial,...
Adenylate cyclase in plasma membranes was inhibited by micromolar concentrations of delta 8-tetrahydrocannabinol and 9-tetrahydrocannabinol levonantradol desacetyllevonantradol. This inhibition noncompetitive for stimulation the enzyme at prostanoid receptor prostaglandin E1 or prostacyclin, peptide secretin vasoactive intestinal peptide. Forskolin-activated adenylate also cannabimimetic agents. Inhibition cannabinoid compounds neither synergistic nor additive with muscarinic...
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...
Standard Gibbs energies of reactions are increasingly being used in metabolic modeling for applying thermodynamic constraints on reaction rates, metabolite concentrations and kinetic parameters. The increasing scope diversity models has led scientists to look genome-scale solutions that can estimate the standard energy all metabolism. Group contribution methods greatly increase coverage, albeit at price decreased precision. We present here a way combine estimations group with more accurate...
The human gut microbiome performs important functions in health and disease. A classic example for host-gut microbial co-metabolism is host biosynthesis of primary bile acids their subsequent deconjugation transformation by the microbiome. To understand these system-level host-microbe interactions, a mechanistic, multi-scale computational systems biology approach that integrates different types omic data needed. Here, we use systematic workflow to computationally model acid metabolism...
Biochemical network reconstructions have become popular tools in systems biology. Metabolicnetwork are biochemically, genetically, and genomically (BiGG) structured databases of biochemical reactions metabolites. They contain information such as exact reaction stoichiometry, reversibility, the relationships between genes, proteins, reactions. Network been used extensively to study phenotypic behavior wild-type mutant stains under a variety conditions, linking genotypes with phenotypes. Such...
The human gut microbiota consists of ten times more microorganisms than there are cells in our body, processes otherwise indigestible nutrients, and produces important energy precursors, essential amino acids, vitamins. In this study, we assembled validated a genome-scale metabolic reconstruction Bacteroides thetaiotaomicron (iAH991), prominent representative the microbiota, consisting 1488 reactions, 1152 metabolites, 991 genes. To create comprehensive model host-microbe interactions,...
Parkinson's disease (PD) is a systemic clinically defined by the degeneration of dopaminergic neurons in brain. While alterations gut microbiome composition have been reported PD, their functional consequences remain unclear. Herein, we addressed this question an analysis stool samples from Luxembourg Study (n = 147 typical PD cases, n 162 controls).All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed self-reporting...
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...
Metabolic network reconstructions represent valuable scaffolds for ‘-omics’ data integration and are used to computationally interrogate properties. However, they do not explicitly account the synthesis of macromolecules (i.e., proteins RNA). Here, we present first genome-scale, fine-grained reconstruction Escherichia coli's transcriptional translational machinery, which produces 423 functional gene products in a sequence-specific manner accounts all necessary chemical transformations....
Abstract Background Metabolic reconstructions (MRs) are common denominators in systems biology and represent biochemical, genetic, genomic (BiGG) knowledge-bases for target organisms by capturing currently available information a consistent, structured manner. Salmonella enterica subspecies I serovar Typhimurium is human pathogen, causes various diseases its increasing antibiotic resistance poses public health problem. Results Here, we describe community-driven effort, which more than 20...
Differentiation of hNESC into functional dopaminergic neurons in phase-guided 3D microfluidic cell culture.
Parkinson's disease (PD) exhibits systemic effects on the human metabolism, with emerging roles for gut microbiome. Here, we integrate longitudinal metabolome data from 30 drug-naive, de novo PD patients and matched controls constraint-based modeling of microbial communities derived an independent, drug-naive cohort, prospective general population. Our key results are (1) trajectory metabolites associated interconversion methionine cysteine via cystathionine differed between controls; (2)...
The application of constraint-based modeling to functionally analyze metagenomic data has been limited so far, partially due the absence suitable toolboxes.
Motivation: Genome-scale metabolic reconstructions summarize current knowledge about a target organism in structured manner and as such highlight missing information. Such gaps can be filled algorithmically. Scalability limitations of available algorithms for gap filling hinder their application to compartmentalized reconstructions. Results: We present fastGapFill, computationally efficient tractable extension the COBRA toolbox that permits identification candidate from universal biochemical...
Abstract Parkinson's disease (PD)‐specific neurons, grown in standard 2D cultures, typically only display weak endophenotypes. The cultivation of PD patient‐specific derived from induced pluripotent stem cells carrying the LRRK2‐G2019S mutation, is optimized 3D microfluidics. automated image analysis algorithms are implemented to enable pharmacophenomics disease‐relevant conditions. In contrast this approach reveals robust High‐content imaging data show decreased dopaminergic differentiation...