Peter Kille

Bio: Peter Kille is an academic researcher from Cardiff University. The author has contributed to research in topics: Lumbricus rubellus & Population. The author has an hindex of 52, co-authored 200 publications receiving 7270 citations. Previous affiliations of Peter Kille include University of Wales & Imperial College London.

Control genes in quantitative molecular biological techniques: the variability of invariance

Abstract: The measurement of transcript levels constitutes the foundation of today's molecular genetics. Independent of the techniques used, quantifications are generally normalised using invariant control genes to account for sample handling, loading and experimental variation. All of the widely used control genes are evaluated, dissecting different methodological approaches and issues regarding the experimental context (e.g. development and tissue type). Furthermore, the major sources of error are highlighted when applying these techniques. Finally, different approaches undertaken to assess the invariance of control genes are critically analysed to generate a procedure that will help to discern the best control for novel experiments.

Protein Kinase CK2 Triggers Cytosolic Zinc Signaling Pathways by Phosphorylation of Zinc Channel ZIP7

Abstract: The transition element zinc, which has recently been identified as an intracellular second messenger, has been implicated in various signaling pathways, including those leading to cell proliferation. Zinc channels of the ZIP (ZRT1- and IRT1-like protein) family [also known as solute carrier family 39A (SLC39A)] transiently increase the cytosolic free zinc (Zn2+) concentration in response to extracellular signals. We show that phosphorylation of evolutionarily conserved residues in endoplasmic reticulum zinc channel ZIP7 is associated with the gated release of Zn2+ from intracellular stores, leading to activation of tyrosine kinases and the phosphorylation of AKT and extracellular signal–regulated kinases 1 and 2. Through pharmacological manipulation, proximity ligation assay, and mutagenesis, we identified protein kinase CK2 as the kinase responsible for ZIP7 activation. Together, the present results show that transition element channels in eukaryotes can be activated posttranslationally by phosphorylation, as part of a cell signaling cascade. Our study links the regulated release of zinc from intracellular stores to phosphorylation of kinases involved in proliferative responses and cell migration, suggesting a functional role for ZIP7 and zinc signals in these events. The connection with proliferation and migration, as well as the activation of ZIP7 by CK2, a kinase that is antiapoptotic and promotes cell division, suggests that ZIP7 may provide a target for anticancer drug development.

Microevolution and ecotoxicology of metals in invertebrates.

Abstract: Risk assessment of metal-contaminated habitats based on responses in the field is complicated by the evolution of local, metal-resistant ecotypes. The unpredictability of occurrence of genetically determined adaptive traits, in terms of site-specific geochemistry, a population's inferred exposure history, and in the physiology of resistance, exacerbates the problem. Micro-evolutionary events warrant the attention of ecotoxicologists because they undermine the application of the bedrock of toxicology, the dose−response curve, to in situ field assessments. Here we survey the evidence for the existence of genetically differentiated, metal-resistant, invertebrate populations; we also describe some of the molecular mechanisms underpinning the adaptations. Quantitative changes in tissue−metal partitioning, and in the molecular and cellular responses (biomarkers) to alterations in internal bioreactive metal pools, are widely accepted as indicators of toxicity and/or exposure in free-living organisms. Both can be modulated by resistance. The understanding that all genomes are intrinsically flexible, with subtle sequence changes in promoter regions or epigenetic adjustments conferring significant phenotypic consequences, is deemed highly relevant. Equally relevant is the systems biology insight that genes and proteins are woven into networks. We advocate that biomarker studies should work toward assimilating and exploiting these biological realities through monitoring the activities of suites of genes (transcriptomics) and their expressed products (proteomics), as well as profiling the metabolite signatures of individuals (metabolomics) and by using neutral genetic markers to genotype populations. Ecotoxicology requires robust tools that recognize the imprint of evolution on the constitution of field populations, as well as sufficient mechanistic understanding of the molecular-genetic observations to interpret them in meaningful environmental diagnostic ways.

'Systems toxicology' approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus

Abstract: New methods are needed for research into non-model organisms, to monitor the effects of toxic disruption at both the molecular and functional organism level. We exposed earthworms (Lumbricus rubellus Hoffmeister) to sub-lethal levels of copper (10–480 mg/kg soil) for 70 days as a real-world situation, and monitored both molecular (cDNA transcript microarrays and nuclear magnetic resonance-based metabolic profiling: metabolomics) and ecological/functional endpoints (reproduction rate and weight change, which have direct relevance to population-level impacts). Both of the molecular endpoints, metabolomics and transcriptomics, were highly sensitive, with clear copper-induced differences even at levels below those that caused a reduction in reproductive parameters. The microarray and metabolomic data provided evidence that the copper exposure led to a disruption of energy metabolism: transcripts of enzymes from oxidative phosphorylation were significantly over-represented, and increases in transcripts of carbohydrate metabolising enzymes (maltase-glucoamylase, mannosidase) had corresponding decreases in small-molecule metabolites (glucose, mannose). Treating both enzymes and metabolites as functional cohorts led to clear inferences about changes in energetic metabolism (carbohydrate use and oxidative phosphorylation), which would not have been possible by taking a 'biomarker' approach to data analysis. Multiple post-genomic techniques can be combined to provide mechanistic information about the toxic effects of chemical contaminants, even for non-model organisms with few additional mechanistic toxicological data. With 70-day no-observed-effect and lowest-observed-effect concentrations (NOEC and LOEC) of 10 and 40 mg kg-1 for metabolomic and microarray profiles, copper is shown to interfere with energy metabolism in an important soil organism at an ecologically and functionally relevant level.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

PHYTOCHELATINS AND METALLOTHIONEINS: Roles in Heavy Metal Detoxification and Homeostasis

Abstract: ▪ Abstract Among the heavy metal-binding ligands in plant cells the phytochelatins (PCs) and metallothioneins (MTs) are the best characterized. PCs and MTs are different classes of cysteine-rich, heavy metal-binding protein molecules. PCs are enzymatically synthesized peptides, whereas MTs are gene-encoded polypeptides. Recently, genes encoding the enzyme PC synthase have been identified in plants and other species while the completion of the Arabidopsis genome sequence has allowed the identification of the entire suite of MT genes in a higher plant. Recent advances in understanding the regulation of PC biosynthesis and MT gene expression and the possible roles of PCs and MTs in heavy metal detoxification and homeostasis are reviewed.

Heavy metals in soils : trace metals and metalloids in soils and their bioavailability

Abstract: Preface.- Contributors.- List of Abbreviations.- Section 1: Basic Principles: Introduction.-Sources of Heavy Metals and Metalloids in Soils.- Chemistry of Heavy Metals and Metalloids in Soils.- Methods for the Determination of Heavy Metals and Metalloids in Soils.- Effects of Heavy Metals and Metalloids on Soil Organisms.- Soil-Plant Relationships of Heavy Metals and Metalloids.- Heavy Metals and Metalloids as Micronutrients for Plants and Animals.-Critical Loads of Heavy Metals for Soils.- Section 2: Key Heavy Metals And Metalloids: Arsenic.- Cadmium.- Chromium and Nickel.- Cobalt and Manganese.- Copper.-Lead.- Mercury.- Selenium.- Zinc.- Section 3: Other Heavy Metals And Metalloids Of Potential Environmental Significance: Antimony.- Barium.- Gold.- Molybdenum.- Silver.- Thallium.- Tin.- Tungsten.- Uranium.- Vanadium.- Glossary of Specialized Terms.- Index.