Expertise

Hub members Have many expertise, covering most of the fields in bioinformatics and biostatistics. You'll find below a non-exhaustive list of these expertise

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Searched keyword : Leishmania

Related people (2)

Christophe BÉCAVIN

Group : GORE - Hub Core

CV Senior Bioinformatician August 2015 – Present : Institut Pasteur, Paris PostDoc fellow 2011 – 2015 : Pascale Cossart’s laboratory, Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris Phd fellow 2007 – 2010 : Institut des Hautes Etudes Scientifiques, ann Ecole Normale Supérieure, Paris Magister of Science, Theoretical Physics 2003 – 2007 : Dynamical systems and statistics of complex matter, Université Paris 7 and Université Paris 6


Keywords
BiophysicsMachine learningModelingProteomicsBiostatisticsDatabases and ontologiesHost-pathogen interactions
Organisms
ListeriaLeishmania
Projects (12)

Related projects (18)

Phylogenetic analysis of the Leishmania HSP70 protein family



Project status : Closed

N/A



Project status : Closed

Bio-informatics support for the LeiSHield project

BioHub LeiSHield project This proposal summarizes the contribution of the BioHub to the LeiSHield action that may be carried out by a single BioHub Leishmania coordinator (Giovanni Bussotti). The coordinator will be implicated in the following actions: 1) Establish the link between LeiSHield members and the BioHub team for all questions regarding data analysis and interpretation. The coordinator will present to the BioHub the bio-informatics needs of the LeiSHield partners. Short (easy) tasks will be answered directly (following the BioHub open door strategy). For more involved tasks i twill be asked to deposit projects via the C3BI web site. 2) Coordinate the setup of an HTseq analysis pipeline, including quality control, read mapping, determination of CNV and SNPs, and data visualization using a combination of tools available at the BioHub, such as SyntView and Listeriomics. A link to Cedric Notredame will be established as scripts for Leishmania have been created there. 3) Oversee the submission of DNA from the different LeiSHield WPs to the IP HTseq facility, follow the progress, store the acquired data, and dispatch the datasets to the corresponding WP leaders. This will be coordinate with the Biomix infrastrcuture. 4) Apply the HTseq analysis pipeline (see point 1) on selected data sets for defined work packages, including WP4 (“Analysis of newly isolated anthroponotic L. donovani s.l. strains from Cyprus and correlation of genotypic profiles to tropism and drug resistance”), WP6 (“Population genetics of Brazilian L. infantum isolates from endemic areas presenting distinct transmission cycle”), WP7 (“Leishmania dovovani genome sequence diversity and disease tropism in the Sudan”), and WP9 (“Systems-wide analysis of Leishmania genomic and transcriptomic adaptation”). 5) Co-organize a course on HTseq data visualization (June 2016) with members of the BioHub team.



Project status : Closed

Gene ontology analysis of RNAseq data from uninfected and Leishmania-infected mouse macrophages

Gene ontology analysis of RNAseq data from uninfected and Leishmania-infected mouse macrophages.  Scientific context During the course of cutaneous or visceral disease in humans or experimental animal models, the resolution of leishmanial infections or the control of parasite growth is dependent on appropriate innate and adaptive immune responses developed by the parasitized host. Leishmania largely evades and subverts these responses by its intracellular life style inside the mammalian host, where the parasites develop into amastigotes mainly within macrophages (BMDMs). We have focused our interest in the BMDM inflammasome and the way Leishmania amastigotes interfere or subvert BMDM inflammatory responses. Our recent data are in favor of an absence of stimulation, even a down-regulation of the inflammasome in BMDMs harboring replicating amastigotes at the gene and protein expression levels. To go further on this, we have performed RNAseq experiments on uninfected and infected BMDMs. This project was done at the “Transcriptome and Epigenome” platform and in close collaboration with the C3BI for normalization and statistical analysis procedures. Objective In the present proposal we will perform a deep analysis of the repartition of modulated genes between the different conditions using these RNAseq data. Using C3Bi expertise we will classify known functions of modulated genes into GO aspects i.e. molecular function, cellular component and biological process, visualize gene annotations and perform statistical analyses for the distribution of the annotated genes over the GO hierarchy for the different gene lists analyzed. Hopefully, these analyses will bring us a better understanding of the mechanisms underlying the subversion of BMDM functions in the innate and adaptive immune response to Leishmania infection which is a prerequisite to design novel anti-parasitic intervention strategies targeting the infected host cell rather than the parasite.



Project status : Closed

SHERLOCK4HAT - WP1.1

African trypanosomes are transmitted by the bite of the tsetse fly and cause the debilitating, and often fatal, neglected tropical disease sleeping sickness, or Human African Trypanosomiasis (HAT). Trypanosoma brucei gambiense, the parasites responsible for 98% of human cases, first reside in the patient blood and skin for months to years before invading the central nervous system, where they cause the neurological symptoms of the disease. HAT is approaching elimination, with the number of cases reported in 2017 dropping to approximately 1,442 from only a dozen African countries. In this context, HAT was included in the WHO roadmap on neglected tropical diseases, with 2020 set as target date for elimination as a public health problem. A secondary goal of zero transmission by 2030 has also been set. These targets have, in part, been encouraged by the success of surveillance efforts that rely on detecting extracellular trypanosomes in human blood. Nevertheless, the reduction in case numbers brings about other challenges. For example, the sensitivity of any diagnostic test diminishes as the disease burden drops, and this is being seen with the serological tests available for HAT. In this context, new highly sensitive and specific diagnostic tools will be required to accurately monitor the occurrence of new cases and the possible emergence of drug-resistant trypanosomes during the elimination phase. Most diagnostic tests currently under development are based on optimization of existing methods that may not combine all the requirements to stand up to the harsh constraints imposed by the elimination phase requirements, especially in terms of sensitivity and specificity. We propose that adapting the recently developed Specific High-sensitivity Enzymatic Reporter unLOCKing (SHERLOCK) technology that combines a CRISPR-Cas system and lateral flow test to trypanosomes will provide the sensitivity and specificity required for a diagnostic test in the elimination and post elimination phases. The SHERLOCK system relies on the collateral effect of Cas13a promiscuous RNA cleavage activity upon target recognition. Combining the collateral effect with pre-amplification of RNAs resulted in rapid RNA detection with attomolar (10^-18 moles/l) sensitivity and single-base mismatch specificity, in a diagnostic setting. This technology has been used to detect specific strains of Zika and Dengue viruses and distinguish pathogenic bacteria in a mixed sample. Furthermore, SHERLOCK reaction reagents can be lyophilized for cold-chain independence and long-term storage and be readily reconstituted on paper for field applications. A lateral flow test for a simple and rapid readout can be easily implemented after a reaction that does not exceed two hours from the sampling step. The first step of this project is to identify promising RNA targets in silico by data mining and multiple alignements of all available transcriptomic data on bloodstream African trypanosomes.



Project status : Closed

The LeiSHield-MATI consortium: Investigating genomic adaptation of Leishmania parasites in endemic areas

Leishmania causes devastating human diseases – leishmaniases - representing an important public health problem in the Mediterranean basin and declared as emerging diseases in the EU due to climate change and population displacement. The LeiSHield-MATI consortium will for the first time investigate in an integrative fashion the complex parasite-vector-host interplay in cutaneous leishmaniasis affecting Morocco, Algeria, Tunisia, and Iran (MATI), using field isolates and human clinical samples. The ultimate goal of our project is to identify genetic factors selected during natural infection and to understand how the complex parasite-vector-animal interaction impacts clinical outcome in infected patients. This goal will be achieved through a highly ambitious secondment plan between all partners, and the organization of courses and workshops to train the next generation of scientists generating a long-term impact on the research capacities in endemic areas. Capitalizing on complementary infrastructures of its EU, African and Asian partners and their expertise in molecular parasitology, epidemiology, systems level analyses, bioinformatics, computational biology, immunology, dermatology, field studies, and public health, our project will drive important innovation in clinical research, strengthen capacities in disease endemic regions, inform authorities on control measures, and raise awareness in all partner countries on this emerging EU public health problem. The highly inter-disciplinary and inter-sectorial structure of LeiSHield-MATI, and its powerful integrative and comparative approach is novel in parasitic systems and will drive a unique bio-marker discovery pipeline for the future development of new prognostic and diagnostic tools, as well as novel preventive and therapeutic measures that will ensure long-term collaboration, promote scientific and commercial self-sustainability of its partners, and will have an important impact to improve public health.



Project status : In Progress