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Conférenciers Invités 8 JS RFMF

Dr Miroslava Cuperlovic-Culf, Dr Emmanuel Gaquerel, Dr Thomas Illig, et Dr Mark Viant

Dr Miroslava Cuperlovic-Culf   et Dr Thomas Illig donneront une conférence plénière dans la session Santé.

Dr Emmanuel Gaquerel et Dr Mark Viant donneront une conférence plénière dans la session Environnement et Écologie chimique.

Cell culture NMR metabolomics and its many applications

Detailed and non-biased analyses of metabolic changes within cells and in extracellular medium can greatly enhance molecular level analysis of cell cultures undergoing variety of treatments. Metabolite concentrations are sensitive markers of genomic characteristics as well as cellular responses to external stimuli. Effects of drugs or toxins on cell cultures can be observed through the changes in metabolite concentrations. When cell cultures are used for the production of biomolecules, metabolomics can aid in optimization of cell growth through routine monitoring of metabolic changes in real time measurements. 

Methods for quantitative NMR metabolomics and combined transcriptomics and metabolomics analysis of cell cultures that were developed in our groups have been extensively used in cancer phenotype analysis, drug testing as well as cell culture growth and applications optimization. In the presentation I will show applications in glioblastoma subtype determination, testing of the effects of drugs targeting several metabolic and epigenetic pathways and finally NMR metabolomics based optimization of vaccine production in cell cultures. 

A metabolomics-centered view on the defensive chemistry of native tobacco species to insect attack

Plant cells are capable of producing an incredibly large spectrum of functionally diverse metabolites, of which many specialized or secondary metabolites have still unknown functions. Research in my group aims at combining high-resolution mass spectrometry (MS)-based metabolomics and genomics resources to explore adjustments in specialized metabolic pathways during plants’ interaction with insects. The model plant we investigate,  Nicotiana attenuata , is a wild tobacco species native from the Great Basin Desert in the USA. This pioneering plant germinates in post-fire habitat and as a consequence represents one of the essential nutritional sources for insect herbivores which re-colonize the ecosystem after fires. By directly “asking the plant” through metabolomics combined with statistical analyses, we discovered and validated the antiherbivore functions of acyclic diterpene glycosides, phenolic-amine derivatives and trichome-based O-acyl sugars, whose biosynthesis is restricted to certain lineages of the Solanaceae. Using multifactorial analysis of integrated transcriptomics-metabolomics time series and self-organizing maps, we developed a novel method to explore transient tissue-specific gene-metabolite co-dynamics during insect herbivory that are activated as signaling spreads throughout the plant. I will present a series of pathway-specific studies in which this method of combining metabolomics and transcriptomics helped in removing much of the guesswork from the process of gene discovery. Some of these significant advances concern the elucidation of the biosynthesis of phenolic-amine derivatives which are produced by diversion of the phenylpropanoid flux and conjugation to spermidine and putrescine backbones. I will finally discuss novel high-resolution MS/MS methods for navigating into natural variation patterns in the defensive metabolism of natural population of wild tobacco.

  • Thomas Illig , Hannover Medical School, Hannover Unified Biobank, Hannover, Allemagne  

Genetic variation of metabolic diseases and metabolomics

Metabolic diseases like obesity or type 2 diabetes are common complex diseases with several different environmental as well as genetic factors involved. This lecture gives a short overview of the genetic characteristics of metabolic diseases. Moreover connections between metabolite-gene associations and their role in metabolic diseases will be presented.

Serum metabolite concentrations allow a direct readout of biological processes and association of specific metabolomic signatures with complex diseases. These metabolites can rather easily be measured in large biobanks. Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. We identified different genetic loci associated with blood metabolite concentrations, of which many exhibit effect sizes that are unusually high for GWAS and account for 10-60% of metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including cardiovascular and kidney disorders, type 2 diabetes and obesity. Our studies advance our knowledge of the genetic basis of metabolic individuality in humans and generate many new hypotheses for biomedical and pharmaceutical research.

  • Mark R. Viant , School of Biosciences, University of Birmingham, Birmingham, Royaume-Uni.

Towards mechanism-based toxicity testing in Daphnia utilising metabolomics approaches

Daphnia (water fleas) are long established model species in both ecology and regulatory toxicology, the former due to their wide geographic distribution and central role in freshwater food webs, and the latter through their important role in determining regulatory criteria by international organisations ( i.e. OECD). This freshwater crustacean represents 8% of all experimental data for aquatic animals within the toxicological databases (Denslow et al . 2007). However the depth of knowledge gained from, for example, OECD acute toxicity and chronic reproductive toxicity tests remains suboptimal, revealing little about mechanisms of toxicity. Recently, transformative opportunities have arisen from the development of genomic resources for this organism, in particular the discovery of the ecoresponsive genome of Daphnia pulex (Colbourne et al . 2011). In addition, other “omics” approaches including transcriptomics, metabolomics and lipidomics have improved our understanding of chemical toxicity. This talk will introduce Daphnia spp. and then describe my lab’s efforts to develop, demonstrate and ultimately exploit the potential of metabolomics to discover predictive molecular markers of toxic stress, both in the fields of chemical toxicology and nanotoxicology. This will include our recent discovery that ZnO nanoparticles can alter the sulfated lipid kairomones excreted by Daphnia, subsequently modulating the morphology of their algal prey, and representing a ‘toxic effect’ that spans two trophic levels. The talk will also incorporate examples of novel computational approaches that are helping to drive forward this environmental metabolomics research program.

N Denslow et al. (2007) In Genomic Approaches for Cross-Species Extrapolation in Toxicology (Eds DiGiulio and Benson).

JK Colbourne et al. (2011)  Science  331, 555-561. 

Rédaction : CDe
Date de création : 20 janvier 2014
Mise à jour : 13 mai 2014
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