We observed that Tgfb1 is upregulated at the transcription level in cells deficient for the four and a half LIM-only protein 2 (FHL2). The upregulation of Tgfb1 leads to increased liver and kidney fibrogenesis in FHL2-/- mice. We have carried out microarray analysis with mouse embryonic fibroblasts derived from FHL2-/- embryos. We would like to have help for the analysis of our microarray data to identify the transcription factors that would be responsible for the upregulation of Tgfb1 expression in FHL2-/- cells. These transcription factors should potentially bind to the murine promoter of Tgfb1.

Transfert des annotations d'un fichier genbank sur une séquence fasta ayant une région de 183 kb inversée par rapport à la séquence parentale

We have described recently a novel mechanism of regulation combining phase variation and attenuation of two pilus operons in Streptococcus gallolyticus . Phase variation occurs  by single-strand mispairing during replication due to the presence of repeats in the leader peptide located immediately upstream of the pilus operon. We wonder if the same mechanism is applicable to other bacterial genes.

Dengue prevention relies primarily on controlling populations of the main mosquito vector, Aedes aegypti, which is failing in many parts of the world because of the lack of sustained commitment of resources and ineffective implementation. Novel entomological approaches to dengue control are being developed that aim at replacing or suppressing mosquito vector populations. Insufficient genomic resources for Ae. aegypti, however, have until now impeded progress in both basic and applied research on this medically important mosquito species. The only available reference genome for Ae. aegypti is a draft that consists of over 4,800 unassembled fragments with incomplete annotation. Moreover, the inbred Ae. aegypti laboratory strain that was sequenced does not universally represent the considerable genetic and ecological diversity of the species worldwide. The large size of the genome and its high content in repeat-rich sequences of transposable elements was a major difficulty to assemble the Ae. aegypti genome sequence. In the present project, we aim to overcome this difficulty using a novel strategy for genome sequencing and assembly. The ultimate goal is to produce several, fully assembled, well-annotated, new Ae. aegypti reference genomes from epidemiologically relevant populations. The expected outcome is a genome reference panel including a catalog of species-wide genetic variation that will significantly improve genomic resources for Ae. aegypti research and help address a broad range of biological questions related to Ae. aegypti vectorial capacity and dengue virus transmission.

A major program of evolutionary and comparative genomics of yeasts has been in progress in my laboratory for many years (see publications). In the next few months (before summer 2015) I need to finish a few comparisons about a new clade to publish as soon as possible.

Currently there is increased focus for developing novel antibacterial strategies. The demand is driven by the rise in antibiotic resistance bacteria and many Gram-negative bacteria are on the list of increasingly drug resistant agents. A major target of successful antibiotics is the bacterial cell wall. The target of these drugs is often defined but what is much less understood is the off-target impact of these very important antibiotics. We designed and executed a mutli-omics strategy centered on the Gram-negative pathogen H. pylori. Our goal is to identify potential 'therapeutically susceptible' pathways associated with the physiological response to cell wall stress.

The rare patients who spontaneously control HIV replication in the absence of therapy show signs of a particularly efficient cellular immune response. To identify the molecular determinants underlying this response, we characterized the TCR repertoire directed at the most immunodominant CD4 epitope in HIV-1 capsid, Gag293. HIV Controllers from the ANRS CO21 CODEX cohort showed a highly skewed TCR repertoire characterized by a predominance of the TRAV24 and TRBV2 variable gene families. Controllers shared public clonotypes at higher frequencies than treated patients, suggesting the implication of particular TCRs in HIV control (Benati D. et al., J Clin Invest 2016).   We propose to test the generality of these findings by characterizing the TCRs specific for a series of immunodominant HIV Gag and Env epitopes, and comparing the frequencies of public clonotypes in groups of HIV Controllers and treated patients. We will then assay the functions of the most prevalent public clonotypes through lentivector-based TCR transfer, and correlate the panel of T cell functions to TCR affinity and frequency.

The genome of the yellow fever mosquito (Aedes Aegypti) is not fully annoyed, and this project aims at discovering novel transcripts using RNAseq data.

We are generating massive amounts of omics data for Leishmania donovani. Anna Zukhova enabled to use the BiNGO module of Cytoskape to perform and visualize our GO enrichment analyses. We would like to continue our collaboration and ask Anna's help to assess the current state of GO annotation of the Leishmania genome and if possible to complete it using domain searches or ortholog mapping from other genomes, including L. major, T. bruce or model organisms such as yeast. We expect that improvement of GO annotation will also us to better reveal enriched GO terms in our datasets and generate testable hypotheses.

The human gene ANOS1, responsible for the X-chromosome-linked form of Kallmann syndrome (a developmental disease affecting the olfactory system), has been identified in 1991 by positional cloning. It is located on the X chromosome short arm (at Xp22.3), close to the STS gene and close to the boundary of the pseudoautosomal region (common to the X and Y sex chromosomes). Since then, orthologous genes have been identified in all animal species (including invertebrates), except in the mouse, rat, and other rodents (an orthologue in the naked mole-rat Heterocephalus glaber is however present in the GeneBank data base). The orthologous STS in the mouse has been identified in the mouse, and is located in the XY pseudoautosomal region in this species. The sequence of the mouse STS is unusually GC-rich and has markedly diverged from the human orthologous sequence, even though the amino acid sequence of the protein is highly conserved. The ANOS1 orthologous genes have not yet been identified in the mouse/rat, although we have been able to detect the encoded protein anosmin-1 in these species, with antibodies directed against the human protein (the orthologous proteins in the mouse and rat have the expected size in western blot analysis, i.e. about 690 amino-acids).

Despite the worldwide importance of malaria due to Plasmodium vivax, there is currently almost no data on the molecular responses of the Anopheles mosquito vectors to this parasite species. Understa

The CRBIP, Centre de Ressources Biologiques de l’Institut Pasteur, is a structure created in 2001 that encompasses the Pasteurian culture collections: the CIP (bacteria collection), the PCC (cyanobact

Nous souhaitons analyser les séquences de sept mutant de Mycobacterium marinum générées par l’utilisation de concentrations croissante d’un antibiotique candidat dont nous ne connaissons pas la cible.