The nematode Caenorhabditis elegans is the best-characterised multicellular eukaryote. Its entire genome is known and the morphology, development and function of each cell lineage mapped in exquisite detail. It offers multiple advantages over other genetic model organisms as it can be grown and manipulated with the speed and ease of a micro-organism, while offering the features of a higher organism such as epithelia, intestine, muscle and a complex sensory system. Most genes and pathways shown to be important in cell, developmental and disease biology are conserved. Therefore, the nematode is an excellent model of biological systems in general, and potentially a powerful tool to unravel human disease.
Studies on single and mixture toxicity: developing and using improved assessment tools and novel methods to reduce uncertainty in current risk assessment and screening methodologies. We have investigated single compounds including PAHs (e.g. benzo[a]pyrene and fluoranthene), herbicides (e.g. atrazine), insecticides (e.g. aldicarb), organophosphate pesticides (e.g. chlorpyrifos), microtoxins (e.g. microcystins), fire retardants (e.g. organobromines), gasses (e.g. hydrogen sulphide), polyphenols (e.g. quercetin and proanthocyanidins), drugs (e.g. Sibutramine and Orlistat), plastics (microfibres), heavy metals (e.g. Cd and Pb). Exposure is rarely a single compound event and therefore we are also interested in assessing additive and synergistic effects of chemical mixtures.
Forward and reverse genetic studies aiming to identify how key players are involved in toxic metal detoxification and essential metal homeostasis. Genes include cadmium-binding metallothioneins (mtl-1, mtl-2) and phytochelatin synthase (pcs-1), copper transporters (cutc-1), zinc metalloproteinase/ transporters (nep-1) and numerous novel metallo-genes/proteins previously not linked to metal trafficking. We are also investigating transgenerational effects of multi-generation exposure.
The study of how an exposure to nanomaterials, such as synthetic zinc, gold or iron nanoparticles, but also carbon black and other natural nanoparticles affect key processes in biology. Depending on the nanomaterial size, surface modification, concentration or exposure route nanoparticles exert positive or negative effects. The ability to differentiate between drivers of positive/negative effects is instrumental for their safe and targeted use.
The International Agency for Research on Cancer (IARC) classifies compounds according to their carcinogenic potential. One candidate is Benzo[a]pyrene (BaP), a Polycyclic aromatic hydrocarbon (PAH) which is generated via the incomplete combustion of fossil fuels and tobacco as well as in polluted air such as diesel exhaust fumes. In higher animals BaP is activated into the carcinogenic metabolite by cytochrome P450 enzymes. Knowing the pathways involved in driving the genotoxic potential of BaP in invertebrate models such as C. elegans is essential to allow us to study their effect on soil organisms but ultimately assess their value as a surrogate model of human exposure. By humanizing the worm (i.e. the introduction of mammalian genes involved in the process of carcinogenesis into the genome of the worm) it is possible to replace, reduce and refine the use of animals in scientific experiments.
Investigating the toxicogenomic effect of commercial obesity drugs and some natural counterparts isolated from plant material on genes and pathways that are conserved from invertebrate to man. We have focussed on lipid metabolism and (ant-obesity effects. In addition, we study life span regulation: Polyphenols, for example, are a group of secondary plant dyes shown to have a positive effect on health and aging across the animal kingdom.
Transcriptomics, RNAseq, knockouts, Mos1-mediated Single Copy insertions (MosSCI), transgenics, Green Fluorescent Protein (GFP), RNAi, Nile Red staining, mutagenesis, qPCR, metabolomics, life cycle analysis, X-ray Absorption Fine Structure (XAFS), X-ray Fluorescence Imaging (XFI), Comet assay, Coherent anti-Stokes Raman Spectroscopy (CARS), etc.