Projets
Programmes Européens
Etat de Vaud
Requérant : Bernard Thorens
Autres collaborateurs : Davide Basco
OntoTransEvol - 615253 EXPLOITATION
Requérant : Henrik Kaessmann
ERC Consolidator Grants
Ontogenetic transcriptome evolution in tetrapods
EVONEURO - 615094 (Exploitation)
Requérant : Richard Benton
ERC Consolidator Grants
Evolution of olfactory circuits
NR-NET 606806 Exploitation
2013 - 2017
Requérant : Béatrice Desvergne
Autres collaborateurs : Tiziana Caputo
NR-NET Marie Curie Initial Training Network - Control of metabolic and inflamatory pathways by nuclear receptors
Betabat - Health-F2-2011-277713 - exploi
2011 - 2015 (48 mois)
Requérant : Bernard Thorens
Autres collaborateurs : Marion Bonnet - Salima Metref - Christopher Dumayne - Dassine Berdous
ERC - 268946 - INSIGHT - Exploitation
2011 - 2016 (60 mois)
Requérant : Bernard Thorens
Autres collaborateurs : Gwenaël Labouebe - Laura Steinbusch - Davide Basco - Philippe Herzog - Alexandre Picard
Glucose homeostasis is controlled by an integrated network of glucose sensing cells, located at several anatomical sites, and which control glucose utilization, endogenous glucose production, energy expenditure, and feeding behavior. The coordination by glucose of these functions depends on secretion of the hormones insulin and glucagon and on the control by the autonomic nervous system of the endocrine pancreas and of the major organs involved in glucose homeostasis: liver, fat and muscle.
Obesity and diabetes can be considered as a consequence of impaired glucose sensing leading to deregulated secretion of pancreatic hormones and abnormal regulation of the autonomic nervous system. Here, we propose an investigative and discovery program to provide new knowledge on three aspects of this integrated glucose sensing network using molecular biology, genetic, genomic and integrated physiological studies in animal models.
Specifically, we will:
1) identify novel mechanisms controlling the glucose competence, proliferation and protection against apoptosis of pancreatic beta-cells, the central node of this integrated glucose sensing network;
2) identify how brain glucose sensors, that are functionally similar to pancreatic beta-cells, control glucose homeostasis and islet function and mass;
3) undertake a genetic-genomic discovery program to identify genetic loci and genes involved in central hypoglycemia detection and the control of counterregulation, a process poorly understood and whose deregulation is the major problem in insulin treatment of both type 1 and type 2 diabetes.
Together these investigations will bring novel information critical for the development of novel therapeutic approach to major metabolic diseases.
SexGenTransEvolution - 242597- FP7 (expl
2010 - 2015
Requérant : Henrik Kaessmann
Mammalian males and females have many phenotypic differences. These differences, collectively referred to as sexual dimorphism, are the consequence of natural and sexual selection for phenotypic traits that affect the fitness of each sex and are encoded in the genome. Part of the underlying genomic differences between the sexes are found on sex specific (the Y) or sex biased chromosomes (the X), while many sexually dimorphic traits probably result from autosomal gene expression differences in sex specific or somatic tissues. However, the origin and evolution of sex-biased genes in mammals has not been studied in detail.
I propose to generate the first detailed qualitative and quantitative transcriptome data using next generation sequencing technologies for a unique collection of germline and somatic tissues from representatives of all major mammalian lineages: placental mammals, marsupials, and the egg-laying monotremes. Together with detailed transcriptome data from birds (the evolutionary sister lineage), complementary experiments (e.g. methylome analyses), and available genomic resources from these species, these unprecedented data will allow an integrated analysis of the origin and functional evolution of mammalian sex chromosomes, the emergence of new sex biased genes, and the evolution of gene expression in germline versus somatic tissues in mammals at large.
The proposed work will thus substantially increase our power to understand how mammalian genomes evolved the capacity to produce such pronounced sexually dimorphic traits. Beyond research pertaining to sex biased genome evolution, our data will represent a unique resource for future investigations of mammalian gene functions and serve as a basis for exploring the evolution of other mammal specific phenotypes.
IMIDIA - 115005- FP7-JU (exploitation)
2010 - 2015 (60 mois)
Requérant : Bernard Thorens
Autres collaborateurs : Danielle Canepa Del Canto-Perri - Guy Niederhäuser - Xavier Berney- Laura Steinbusch
Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in diabetes
CNVIMPACTGEXP - 255588- FP7 (exploitatio
2010 - 2015
Requérant : Emilie Ait Yahya Graison
Copy number variation (CNV) of DNA segments has recently been identified as a major source of genetic diversity, but a comprehensive understanding of the phenotypic effect of these structural variations is only beginning to emerge. An extensive map of CNV in wild mice and inbred strains has been established by the host group. These variable regions cover ~11% of their autosomal genome. CNVs are suggested to shape tissue transcriptomes on a global scale and thus represent a substantial source for within-species phenotypic variation. In this context, we address three major research objectives all regarding the impact of structural variants on different aspects of the transcriptome.
To unravel the effects of CNVs on expression at the nucleotide rather than locus level we propose to use RNA-seq to monitor expression changes of both coding and non-coding RNAs that map to or close to genomic regions that vary in copy numbers in multiple tissues of the three mouse inbred strains (129S2, DBA/2J, C57BL/6J). These will be compared to changes in the abundance of transcripts that lie outside of CNV regions. Secondly, we will use RNA-seq data to identify and characterize alternative splicing events that are either tissue- or strain-specific, as well as determine whether copy number polymorphisms affect this process. Thirdly, we will investigate allelic imbalance at genome-wide scale and check if this phenomenon is more likely to occur in CNVs.
This work should:
- give an unprecedented global and precise view of the mouse transcriptome;
- produce the first transcriptome comparison at the nucleotide level of normal individuals of a population;
- help to gauge the influence of CNVs on the transcriptome and
- provide the first assessment of allelic imbalance at genome-wide scale.
Contrats et Mandats
Role of PPARbeta in exercise tolerance
Organisme subventionnaire : GlaxoSmithKline, Uxbridge, UK
Requérant : Walter Wahli
Role of PPARs in gut differentiation
Organisme subventionnaire : Fonds Nestlé
