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3rd joint call on PathoGenoMics:

Members of the Scientific Advisory Board

The following proposals have been suggested for funding and are currently subject to contract negotiations on national level.

Proposals suggested for funding

Acronym Title Partici-
(Coordinator / Principal investigators
3 GeMoA A genome-wide approach for characterizing the mode of action of novel compounds against Tuberculosis ES Marc A. Marti-Renom
DE Matthias Wilmanns
ES LLuís Ballell
FR Olivier Neyrolles
FR Brigitte Gicquel
Infection with Mycobacterium tuberculosis (Mtb), the causing agent of Tuberculosis (TB) is best described as a dynamic balance between activation and suppression of host responses, orchestrated by complex interactions between multiple host and bacterial components. Therefore, single target approaches for drug identification, have achieved limited success. The present project addresses this limitation by applying genomewide approaches to characterize the mechanism of action of selected chemical compounds with activity against Mtb. This line of research can lead to unexplored new modes of action against Mtb and a series of potential targets and corresponding compounds to be further explored as treatment against TB.
5 ARMSA Global analysis of antisense regulatory mechanisms in Staphylococcus aureus ES Iñigo Lasa
FR Pascale Romby
FR Francois Vandenesh
PT Susana Domingues
ES José R. Penadés
This research project is dedicated to exploring the effects of antisense RNA transcription on gene expression in Staphylococcus aureus, a leading cause of nosocomial and community acquired infections. The project will determine the transcriptome map of S. aureus using tiling arrays and deep sequencing strategies to identify overlapping transcription. The resulting map will be used to analyze the stability of overlapping transcripts; the effect of active replication of pathogenicity islands (PI) or phages on the bacterial transcriptome; and antisense mediated gene regulation in bacterial populations and at single cell level. Mutants deficient in particular antisense transcripts or in proteins involved in antisense mediated gene regulation will be assayed. This work is also anticipated to provide novel S. aureus targets for antibiotics.
7 AspBIOmics Biomarkers for prevention, diagnosis and response to therapy of invasive aspergillosis DE Hermann Einsele
DE Axel Brakhage
FR Jean Paul Latgé
FR Alain Troesch
AT Cornelia Lass-Floerl
ES Manuel Jurado Chacon
Invasive aspergillosis (IA) infection-associated mortality incidence is growing and increasingly affecting a broader range of patient groups. A major problem in the management of IA is the poor diagnosis. This consortium proposes to develop and evaluate an efficient diagnostic platform for IA, based on a battery of in vitro assays for a comprehensive multimodality analysis, combining the detection of Aspergillus elements (RNA, polysaccharides, proteins), host factors including cytokine profiles and host genetic susceptibility. This strategy also has the potential to identify patients who are at a high risk of IA infection and to monitor treatment progression.
15 CANDICOL Understanding colonisation and the transition to pathogenic dissemination by Candida species: towards early diagnostic and therapeutic approaches HU Attila Gacser
FR Christophe d'Enfert
DE Uwe Groß
DE Bernhard Hube
AT Karl Kuchler
AT Thomas Lion
The CANDICOL project aims to dissect the genetic and transcriptional underpinnings of the transition of the main pathogenic Candida species from commensalism to host dissemination. The project will identify and classify shared or distinguishing attributes of these species by establishing and optimizing research model systems, and studying fungal and host transcriptional patterns, genetic networks and fungal antigens associated with infections. Novel mutant strain collections will be developed and will help in identifying sets of fungal genes crucial for colonisation and dissemination. This research is important stepping stone in developing novel diagnostic tools for discriminating and predicting stages of fungal infection as well as identifying feasible targets for novel anti-fungal therapeutic.
24 OXYstress Human fungal pathogens under oxygen stress: adaptive mechanisms to hypoxia and reactive oxygen species and their consequences for host interaction and therapy DE Joachim F. Ernst
ES Jesus Pla
DE Axel Brakhage
ES Enrique Herrero
AT Cornelia Lass-Flörl
DE Christian Leggewie
The proposal is based on the fact that invasive pathogens frequently interact with the human host in niches low in oxygen, often associated with increased levels of reactive oxygen species (ROS) and carbon dioxide. During systemic infections, pathogens often encounter and adapt to numerous hypoxic niches within tissues, organs and cells. The proposal unites an international panel of experts to clarify and exploit the molecular mechanisms of fungal responses and host interactions under oxygen stress in vitro and in experimental models of infection. In particular, differences between host-pathogen interactions under hypoxia and normoxia will be established. The study includes the development of novel fluorescent reporters for hypoxic infections, and the identification of both diagnostic biomarkers and novel targets for antifungal drugs.
25 CELLPATH Characterisation of host cell pathways altered by effectors of Brucella, Chlamydia, and Coxiella: identification of novel therapeutic targets PT Luís Jaime Mota
PT João Paulo Gomes
DE Anja Lührmann
ES Carmen Plasencia
ES Isabel Rodriguez-Escudero
FR Suzana Salcedo
The purpose of this project is to characterise the molecular and cellular function of effector proteins from Brucella spp., Chlamydia trachomatis, and Coxiella burnetii, all relatively uncharacterised intracellular Gram-negative bacterial pathogens. The research will focus on the host cell signaling pathways targeted by effectors of Brucella, Chlamydia, and Coxiella and on the possible correlation of the mode of action of the effectors with their gene sequence variability and expression levels among different strains, including recent clinical isolates. The results may lead to novel therapeutic approaches, vaccines and diagnostics.
32 MobileGenomics Impact of mobile genetic elements and horizontal gene transfer on bacteria-host adaptation: a genomics view FR Carmen Buchrieser
FR Philippe Glaser
DE Ulrich Dobrindt
DE Sören Schubert
AT Joachim Reidl
FR Tamara Smokvina
This project aims to study horizontal gene transfer (HGT) and mobile genetic elements (MGE) in the human gut environment and in the upper and lower respiratory tracts. Commensals, probiotics and important opportunistic bacterial pathogens are present in both niches. The study will analyze niche-specific representatives of these three classes. The aims of this project are to increase basic knowledge on genome variability, on the mechanism leading to this variability and on the impact it has on host adaptation, colonization and virulence. The research is expected to impact our understanding on niche adaptation, bacterial survival in harsh conditions, colonization and virulence acquisition related to MGE and HGT, and to help decipher the impact of antibiotics and screen for more efficient probiotics and vaccines.
35 HELDIVPAT Helicobacter pylori diversity in pathogenesis, antibiotic resistance, and evasion from natural and vaccine-induced immune responses DE Sebastian Suerbaum
FR Ivo G. Boneca
PT José Carlos Machado
DE Christine Josenhans
DE Rainer Haas
DE Peter Maltertheiner
Helicobacter pylori chronically infects more than one half of the world’s human population, causing chronic gastritis and complications such as peptic ulcer disease and malignancies. Treatment is undermined by a rising rate of antibiotic resistance, lack of vaccine and significant genetic diversity and variability. The HELDIVPAT project, building on the results of a previous ERA-NET PathoGenoMics funded project, HELDIVNET, will explore how the genetic diversity of H. pylori is connected to pathogenesis, its ability to evade immune responses and resistance to antibiotics. The consortium partners have access to unique resources, including a novel strain collection from a vaccine trial and a globally representative collection of MLST-characterized H. pylori strains.
42 LISTRESS Analysis of the cellular mechanisms underlying the early response of the host to stress induced by Listeria infection DE Trinad Chakraborty / Torsten Hain
FR Pascale Cossart / Marc Lecuit
DE Jürgen Wehland / Lothar Jänsch
ES Francisco García-del Portillo
PT Didier Cabanes
IL Yair Aharonowitz / Anat A. Herskovits
This project aims to analyse the role of the Listeria factors that induce post-translational modifications and organelle remodelling in order to overcome host recognition and response. Bacterial ligands as well as their intracellular pattern recognition receptors (PRRs) will be identified using functional genomic strategies, 3D- and 2-photon imaging technologies, and clinical material from patients with inflammatory bowel disease harbouring mutations in predisposition loci. Interacting targets and downstream events leading to the induction of cell autonomous defences and innate immune signalling pathways will also be pursued, and interactions between Listeria effector ligands and host proteins will be mapped.
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