A5040102543- Genetics, Aging, and Longevity in Model Organisms
- Gut microbiota and health
- Circadian rhythm and melatonin
- Tryptophan and brain disorders
- 3D Printing in Biomedical Research
- Mitochondrial Function and Pathology
- Redox biology and oxidative stress
- Trace Elements in Health
- Dietary Effects on Health
- Autophagy in Disease and Therapy
- Metabolomics and Mass Spectrometry Studies
- SARS-CoV-2 and COVID-19 Research
- Iron Metabolism and Disorders
- Biochemical effects in animals
- Heavy Metal Exposure and Toxicity
- Spaceflight effects on biology
- Metabolism, Diabetes, and Cancer
- Clostridium difficile and Clostridium perfringens research
- Endoplasmic Reticulum Stress and Disease
- Nanoparticles: synthesis and applications
- Cancer, Hypoxia, and Metabolism
- Genomics, phytochemicals, and oxidative stress
- Sex and Gender in Healthcare
- Folate and B Vitamins Research
- Health, Environment, Cognitive Aging
Imperial College London
2019-2025
Hammersmith Hospital
2019-2025
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2021-2025
University of Cologne
2021-2025
MRC London Institute of Medical Sciences
2019-2024
Medical Research Council
2024
Institute of Structural and Molecular Biology
2015-2021
University College London
2011-2021
Birkbeck, University of London
2017-2019
MRC Unit for Lifelong Health and Ageing
2011-2017
The biguanide drug metformin is widely prescribed to treat type 2 diabetes and metabolic syndrome, but its mode of action remains uncertain. Metformin also increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli. This bacterium exerts complex nutritional pathogenic effects on nematode predator/host that impact health aging. We report by altering microbial folate methionine metabolism. Alterations metformin-induced longevity mutation worm synthase (metr-1)...
Hydrogen peroxide (H2O2) is central to mitochondrial oxidative damage and redox signaling, but its roles are poorly understood due the difficulty of measuring H2O2 in vivo. Here we report a ratiometric mass spectrometry probe approach assess matrix levels The probe, MitoB, comprises triphenylphosphonium (TPP) cation driving accumulation within mitochondria, conjugated an arylboronic acid that reacts with form phenol, MitoP. Quantifying MitoP/MitoB ratio by liquid chromatography-tandem...
Metformin is the first-line therapy for treating type 2 diabetes and a promising anti-aging drug. We set out to address fundamental question of how gut microbes nutrition, key regulators host physiology, affect effects metformin. Combining two tractable genetic models, bacterium E. coli nematode C. elegans, we developed high-throughput four-way screen define underlying host-microbe-drug-nutrient interactions. show that integrate cues from metformin diet through phosphotransferase signaling...
Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, bacterium E. coli and nematode C. elegans, we performed three-way high-throughput screens that unraveled complexity underlying host-microbe-drug interactions. report microbes can bolster or suppress effects fluoropyrimidines...
For cells the passage from life to death can involve a regulated, programmed transition. In contrast cell death, mechanisms of systemic collapse underlying organismal remain poorly understood. Here we present evidence cascade involving calpain-cathepsin necrosis pathway that drive in Caenorhabditis elegans. We report is accompanied by burst intense blue fluorescence, generated within intestinal necrotic pathway. Such fluorescence marks an anterior posterior wave cytosolic acidosis. This...
The superoxide free radical (O(2)(•-)) has been viewed as a likely major contributor to aging. If this is correct, then dismutase (SOD), which removes O(2)(•-), should contribute longevity assurance. In Caenorhabditis elegans, overexpression (OE) of the cytosolic Cu/Zn-SOD, sod-1, increases life span. But increase caused by enhanced antioxidant defense? sod-1 OE did not reduce measures lipid oxidation or glycation and actually increased levels protein oxidation. effect on span was dependent...
Loss of proteostasis is a fundamental process driving aging. Proteostasis affected by the accuracy translation, yet physiological consequence having fewer protein synthesis errors during multi-cellular organismal aging poorly understood. Our phylogenetic analysis RPS23, key in ribosomal decoding center, uncovered lysine residue almost universally conserved across all domains life, which replaced an arginine small number hyperthermophilic archaea. When introduced into eukaryotic RPS23...
Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here increased necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and sufficient on its own increase lifespan. first established the well-characterised extension associated with deletion insulin receptor substrate chico was completely abrogated downregulation essential gene Atg5 . next directly induced over-expressing major kinase Atg1 found mild...
According to the mitochondrial theory of aging, dysfunction increases intracellular reactive oxidative species production, leading oxidation macromolecules and ultimately cell death. In this study, we investigated role methionine sulfoxide reductase B2 in protection against stress. We report, for first time, that overexpression mitochondria acute T-lymphoblastic leukemia MOLT-4 line, which A is missing, markedly protects hydrogen peroxide-induced stress by scavenging oxygen species. The...
Iron-catalyzed generation of free radicals leads to molecular damage in vivo, and has been proposed contribute organismal ageing. Here we investigate the role iron ageing nematode Caenorhabditis elegans. Media supplementation with Fe(III) increased levels as detected by continuous-wave electron paramagnetic resonance spectroscopy elevated expression iron-sensitive reporter transgene pftn-1::gfp. Increased caused protein oxidation hypersensitivity tert-butyl hydroperoxide (t-BOOH) given 9 mM...
Aging (senescence) includes causal mechanisms (etiologies) of late-life disease, which remain poorly understood. According to the recently proposed hyperfunction theory, based on older theory antagonistic pleiotropy, senescent pathologies can arise from futile, post-reproductive run-on processes that in early life promote fitness. Here we apply this idea investigate etiology reproductive system Caenorhabditis elegans hermaphrodites, particularly distal gonad degeneration and disintegration....
Abstract Genetic and environmental factors are key drivers regulating organismal lifespan but how these impact healthspan is less well understood. Techniques capturing biomechanical properties of tissues on a nano-scale level providing new insights into disease mechanisms. Here, we apply Atomic Force Microscopy (AFM) to quantitatively measure the change in associated with ageing Caenorhabditis elegans addition high-resolution topographical images cuticle senescence. We show that distinct...
Pharmaceutically active compounds enter soils via wastewater reuse and biosolid application. A ubiquitous drug present in is carbamazepine, a frequently prescribed anti-convulsant. Its mode of action not species-specific affects the nervous system non-target organisms, including most likely soil dwelling earthworms, which turn has potential to negatively impact quality. In this project, were amended with carbamazepine explore uptake dynamics resultant changes molecular life cycle endpoints...
Abstract Diet is believed to be an important mediator of oncogenesis and response anti-cancer therapies, although no evidence-based dietary guidelines exist for patients with cancer. Limiting protein intake can suppress tumor growth by both inducing nutrient stress enhancing anti-tumor immunity. However, little known about the impact reducing on efficacy chemotherapy, most widely used treatment. Here, we present evidence that in mice 50% stops established tumors, parallel a DNA damage....
Folates act as co-factors for transfer of one-carbon units nucleotide production, methylation and other biosynthetic reactions. Comprehensive profiling multiple folates can be achieved using liquid chromatography tandem mass spectrometry, enabling determination their relative abundance that may provide an indication metabolic differences between cell types. For example, lines exposed to methotrexate showed a dose-dependent elevation dihydrofolate, consistent with inhibition dihydrofolate...
Caenorhabditis elegans has become a key model organism within biology. In particular, the transparent gut, rapid growing time, and ability to create defined gut microbiota make it an ideal candidate for understanding engineering host microbiota. Here we present development of experimental that can be used characterize whole-cell bacterial biosensors in vivo. A dual-plasmid sensor system responding isopropyl β-d-1-thiogalactopyranoside was developed fully characterized vitro. Subsequently,...