A5051158497- Microbial Metabolic Engineering and Bioproduction
- Malaria Research and Control
- Mosquito-borne diseases and control
- Microbial Natural Products and Biosynthesis
- Bioinformatics and Genomic Networks
- SARS-CoV-2 and COVID-19 Research
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Fungal and yeast genetics research
- Gut microbiota and health
- Antimicrobial Resistance in Staphylococcus
- Bacteriophages and microbial interactions
- Evolution and Genetic Dynamics
- Pregnancy and preeclampsia studies
- COVID-19 Clinical Research Studies
- Vector-borne infectious diseases
- Drug Transport and Resistance Mechanisms
- Bacterial Genetics and Biotechnology
- Animal Virus Infections Studies
- Antibiotic Resistance in Bacteria
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Mycobacterium research and diagnosis
- Genetics, Aging, and Longevity in Model Organisms
- Berberine and alkaloids research
United Arab Emirates University
2021-2025
University of Warwick
2016-2023
University of Leicester
2023
University of Cambridge
2014-2017
Radboud University Nijmegen
2012-2015
Radboud University Medical Center
2012-2015
Radboud Institute for Molecular Life Sciences
2015
Emory University
2014
Centers for Disease Control and Prevention
2013
Atlanta Research and Education Foundation
2013
Inflammatory bowel disease (IBD), is a debilitating group of chronic diseases including Crohn's Disease (CD) and ulcerative colitis (UC), which causes inflammation the gut affects millions people worldwide. At different taxonomic levels, structure microbiota significantly altered in IBD patients compared to that healthy individuals. However, it unclear how these IBD-affected bacterial groups are related other common bacteria gut, they connected across conditions at global scale.In this...
Abstract Microbial communities are composed of cells varying metabolic capacity, and regularly include auxotrophs that lack essential pathways. Through analysis for amino acid biosynthesis pathways in microbiome data derived from >12,000 natural microbial obtained as part the Earth Microbiome Project (EMP), study auxotrophic–prototrophic interactions self-establishing metabolically cooperating yeast (SeMeCos), we reveal a imprinted mechanism links presence to an increase gains...
Plasmids are mobile genetic elements that play a key role in the evolution of bacteria by mediating genome plasticity and lateral transfer useful information. Although originally considered to be exclusively circular, linear plasmids have also been identified certain bacterial phyla, notably actinomycetes. In some cases, engage with chromosomes an intricate evolutionary interplay, facilitating emergence new configurations recombination or plasmid integration. Genome sequencing Streptomyces...
During the lifetime of a fermenter culture, soil bacterium S. coelicolor undergoes major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using specifically designed Affymetrix genechip and high-resolution time-series fermenter-grown samples. Surprisingly, we find that actually consists multiple finely orchestrated switching events. Strongly coherent clusters genes show drastic changes in already many hours before...
Genome-metabolism interactions enable cell growth. To probe the extent of these and delineate their functional contributions, we quantified Saccharomyces amino acid metabolome its response to systematic gene deletion. Over one-third coding genes, in particular those important for chromatin dynamics, translation, transport, contribute biosynthetic metabolism. Specific signatures characterize genes similar function. This enabled us exploit metabolomics connect metabolic regulators effectors,...
Alzheimer's disease (AD) is the most common cause of adult dementia. Yet complete set molecular changes accompanying this inexorable, neurodegenerative remains elusive. Here we adopted an unbiased lipidomics and metabolomics approach to surveying frozen frontal cortex samples from clinically characterized AD patients (n = 21) age-matched controls 19), revealing marked differences between them. Then, by means metabolomic pathway analysis, incorporated novel information into known biochemical...
Metabolites can inhibit the enzymes that generate them. To explore general nature of metabolic self-inhibition, we surveyed enzymological data accrued from a century experimentation and generated genome-scale enzyme-inhibition network. Enzyme inhibition is often driven by essential metabolites, affects majority biochemical processes, executed structured network whose topological organization reflecting chemical similarities exist between metabolites. Most inhibitory interactions are...
Metabolite exchange among co-growing cells is frequent by nature, however, not necessarily occurring at growth-relevant quantities indicative of non-cell-autonomous metabolic function. Complementary auxotrophs Saccharomyces cerevisiae amino acid and nucleotide metabolism regularly fail to compensate for each other's deficiencies upon co-culturing, a situation which implied the absence metabolite interactions. Contrastingly, we find that yeast colonies maintain rich exometabolome prefer...
Cardiolipin (CL) is a phospholipid specific for mitochondrial membranes and crucial many core tasks of this organelle. Its acyl chain configurations are tissue specific, functionally important, generated via post-biosynthetic remodeling. However, process lacks the necessary specificity to explain CL diversity, which especially evident highly compositions in mammalian tissues. To investigate so far elusive regulatory origin homeostasis mice, we combine lipidomics, integrative transcriptomics,...
Metabolism is deeply intertwined with aging. Effects of metabolic interventions on aging have been explained intracellular metabolism, growth control, and signaling. Studying chronological in yeast, we reveal a so far overlooked property that influences via the exchange metabolites. We observed metabolites exported by young cells are re-imported chronologically cells, resulting cross-generational interactions. Then, used self-establishing metabolically cooperating communities (SeMeCo) as...
Abstract Background The transition from exponential to stationary phase in Streptomyces coelicolor is accompanied by a major metabolic switch and results strong activation of secondary metabolism. Here we have explored the underlying reorganization metabolome combining computational predictions based on constraint-based modeling detailed transcriptomics time course observations. Results We reconstructed stoichiometric matrix S. , including antibiotic biosynthesis pathways, performed flux...
Low vitamin B12 during pregnancy is associated with higher maternal obesity, insulin resistance (IR), and gestational diabetes mellitus. a key cofactor in one-carbon metabolism. We hypothesize that plays role epigenetic regulation by altering circulating microRNAs (miRs) adipocyte differentiation results an adverse metabolic phenotype. Human preadipocyte cell line (Chub-S7) was differentiated various concentrations: control (500 nM), low (0.15 no (0 nM). Maternal blood samples (n = 91)...
Abstract Background Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), affect millions of people worldwide with increasing incidence. Objectives Several studies have shown a link between gut microbiota composition IBD, but results are often limited by small sample sizes. We aimed to re‐analyze publicly available fecal data from IBD patients. Methods extracted original 16S rRNA amplicon sequencing 45 cohorts patients healthy individuals using the...
RTS,S is the most advanced malaria vaccine candidate, currently under phase-III clinical trials in Africa. This Plasmodium falciparum contains part of central repeat region and complete C-terminal T cell epitope (Th2R Th3R) circumsporozoite protein (CSP). Since naturally occurring polymorphisms at candidate loci are critical determinants protective efficacy vaccines, it imperative to investigate these field isolates. In this study we have investigated genetic diversity repeat, N-terminal...
Significance We have recently identified the sequence of ether lipid-cleaving enzyme alkylglycerol monooxygenase. Like nitric oxide synthases and aromatic amino acid hydroxylases, monooxygenase needs tetrahydrobiopterin as cofactor. Whereas former enzymes well-established roles in cell, physiology is still not clear. Here we show its regulation murine macrophage differentiation dependence on cofactor live macrophage-like RAW264.7 cells. Upon modulation activity key biosynthesis, observe...
Bile acid diarrhoea (BAD) is a common disorder resulting from increased loss of bile acids (BAs), overlapping irritable bowel syndrome with (IBS-D). The gut microbiota metabolises primary BAs to secondary BAs, differing impacts on metabolism and homeostasis. aim this study was profile the microbiome, metabolic products in BAD. Patients BAD diagnosed by SeHCAT testing, were compared other IBS-D patients, healthy controls. Faecal 16S ribosomal RNA gene analysis undertaken. short chain fatty...
Abstract The Staphylococcus aureus type VII secretion system (T7SS) exports several proteins that are pivotal for bacterial virulence. mechanisms underlying T7SS-mediated staphylococcal survival during infection nevertheless remain unclear. Here we report S. lacking T7SS components more susceptible to host-derived antimicrobial fatty acids. Unsaturated acids such as linoleic acid (LA) elicited an increased inhibition of mutants effectors EsxC, EsxA and EsxB, or the membrane-bound ATPase...
The first definitive hematopoietic progenitors emerge through the process of endothelial-to-hematopoietic transition in vertebrate embryos. With molecular regulators for this worked out, role metabolic pathways used remains unclear. Here, we performed nano–LC-MS/MS–based proteomic analysis and predicted a switch from glycolytic to oxidative state upon transition. Mitochondrial activity, glucose uptake, flux supported hypothesis. Systemic inhibition lactate dehydrogenase A (LDHA) increased...
The antifolate drugs sulfadoxine and pyrimethamine are commonly used to treat Plasmodium falciparum malaria. However, they can also affect the vivax parasite if it coexists with P. falciparum, as both species have common drug targets. Resistance arises due point mutations in target enzymes of respective parasite. To assess cross-species impact treatment, we describe here dihydrofolate reductase (DHFR) among field isolates falciparum. overall DHFR mutation rate for was lower than that...
Summary To increase production of the important pharmaceutical compound clavulanic acid, a β‐lactamase inhibitor, both random mutagenesis approaches and rational engineering Streptomyces clavuligerus strains have been extensively applied. Here, for first time, we compared genome‐wide gene expression an industrial S. strain, obtained through iterative mutagenesis, with that wild‐type strain. Intriguingly, found majority changes contributed not to complex rewiring primary metabolism but...