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2nd joint call on PathoGenoMics:

“Applied pathogenomics: Prevention, diagnosis, treatment and monitoring of infectious diseases in humans”

 

Coordinators of the 2nd joint call projects:
Matthias Maaß, Sophie de Bentzmann, Thomas Rattei, Vitor Martins dos Santos (for Stephan Ott), Alexander Mellmann, Torsten Hain, Ulrich Dobrindt, Maja Rupnik, Olaf Kniemeyer (for Axel Brakhage), José Antonio Bengoechea, Pavel Kovarik, Ulrich Vogel
 
Kick-off Meeting at the Villa Vigoni, 12th 2009

Funded Projects of the 2nd joint call:

 

Project No. Coordinator Project Partners (Short) Title
10 Ulrich Vogel Seppo Meri
Muhamed-Kheir Taha
Jan Poolman
Genome wide screening of the human pathogen Neisseria meningitidis for proteins enhancing serum resistance and evaluation of their vaccine potential
Neisseria meningitidis (meningococcus) continues to be a major health threat by causing septicaemia and meningitis with a case fatality rate of ~10%. A major line of immune defence against meningococci is the serum complement system, but certain serogroups are able to evade the immune response, leading to a limited strain coverage of current vaccines. 4 research groups from 3 countries undertook to develop novel vaccines that will generate antibodies capable of blocking bacterial factors involved in immune escape. To this end, a systematic genomic approach is proposed, in order to uncover complement regulatory molecules in meningococci.
12 José Antonio Bengoechea Philippe Sansonetti
Thomas F. Meyer
Thomas Rudel
Carmen Buchrieser
Joerg Poetzsch
Functional genomics of host-pathogen interactions using high-throughput screenings: a novel approach towards identifying therapeutic/prophylactic targets
The progress of infections is the joint outcome of both pathogen and host-related features. This project, comprising 6 research groups from 3 countries, aims to identify novel pathogen determinants targeting crucial host functions, using genomic, bioinformatics and high-throughput screening methods.
The group will focus on 5 important human pathogens: M. tuberculosis, L. pneumophila, H. pylori, N. gonorrhoeae and K. pneumoniae. The project complements ongoing work in the RNAi-Net, which focuses on the host side. This research program is expected to lead to the development of innovative therapies based on the modulation of the hostpathogen interface.
16 Ulrich Dobrindt Jörg Hacker
Timo Korhonen
Levente Emõdy
Istvan Wittmann
Eliora Ron
Catharina Svanborg; Björn Wullt
Pathogenomic approach to explore the use of bacterial interference as alternative treatment of recurrent urinary tract infections
There is a strong need for alternatives to current antibiotic treatment, such as "bacterial interference", vaccination and new drugs. This project brings together 6 research groups from 4 countries to understand the molecular basis of asymptomatic bacteriuria (ABU) and to apply genomic approaches to exploit ABU E.coli isolates for "bacterial interference" to combat recurrent UTI. The acquired data will also provide additional information on bacterial traits that are associated with symptomatic infection, thus helping to identify new vaccine or drug targets for combating UTI. The geno- and phenotypic stability of isolate 83972 will be studied allowing its further improvement for bacterial interference.
21 Sophie de Bentzmann Patrick Plésiat
Juan Luis Ramos
Isabel Sá-Correia
Soeren Molin
Catherine Nguyen
Matilde Fernández
ADHRES-Signature Project
Targeting bacterial virulence rather than survival may offer a reduced selection pressure for drug-resistant mutations. The most common virulence trait is abacterial community called biofilm, which is highly resistant to antibiotic treatment and host defences. P. aeruginosa, P. putida and B. cepacia complex are particularly problematic, since they constantly exist as biofilm. The goal of this consortium, of 7 research groups from 4 countries, is to identify a core set of genes involved in biofilm and antimicrobial resistance important in in vivo infectious situation and relevant to clinical pathogenicity. Such a gene list is patentable, and amenable to screening by chips or any other technique for mRNA detection.
29 Torsten Hain Maja Rupnik
Axel Hartke
Bernd Kreikemeyer
Susanne Engelmann
Sonja Vorwerk
Thomas Hartsch
sncRNAomics - High throughput comparative sncRNAome analysis in major Gram-positive human pathogenic bacteria: functional characterization by a systems biology approach and peptide nucleic acid drug design
Novel anti-infectives are of high priority for global health care. Small non-coding RNAs (sncRNAs) in bacteria are an emerging class of new gene expression regulators, but their role in colonisation and pathogenicity is largely unknown. The consortium brings together 7 research groups from 3 countries, thus combining novel high-throughput sncRNA screening methods, whole-genome transcriptomics and proteomics and bioinformatics coupled with molecular characterization methods to provide new data regarding sncRNAs in major high-risk Grampositive microbes (e.g. Staphylococcus, Streptococcus, Enterococcus, Clostridium and Listeria). Potential new drugs and diagnostic biomarkers will be validated using tissue-culture and subsequently in in-vivo models.
35 Antonio Di Pietro Hubertus Haas
Gerhard Braus
Sven Krappmann
Ana Conesa
Roland Beffa
Transcriptional networks controlling virulence in filamentous fungal pathogens (TRANSPAT)
Invasive fungal infections in immunocompromised patients are on the rise, in particular of filamentous species (moulds). Still, little is understood about the ability of filamentous fungi to survive in the hostile environment of mammalian blood. Even less is understood about their clinical resistance to antifungal agents. TRANSPAT, comprising 6 research groups from 4 countries, aims to integrate genetic, genomic and bioinformatic tools to uncover clinically relevant transcriptional networks in fungi, exploiting the complete genome sequences and mutant collections of A. fumigatus and F. oxysporum. This approach will identify gene sets showing altered expression during invasive infection and/or exposure to antifungals.
36 Axel Brakhage Jean-Paul Latgé
Emilia Mellado Terrado
Fernando Pelaez
Dominique Costantini
The cell wall as a target to improve antifungal therapy against Aspergillosis
Aspergillus fumigatus infections have dramatically increased worldwide. Due to the limited number and efficacy of antifungal drugs, the mortality from Invasive Aspergillosis (IA) is very high. The cell wall of A. fumigatus is a major drug target. This project aims at elucidating the relationship between signal transduction cascades and cell wall biosynthesis in A. fumigatus, leading also to the identification of drug-resistance mechanisms. Functional genomic analyses, large-scale mutant libraries and genetic reporter systems will be the key methodologies, employed by 5 research groups from 3 countries. The tools generated may lead to new, more efficient drugs.
37 Maja Rupnik Bruno Dupuy
Frederic Barbut
Adriano O. Henriques
Alexander Indra
Wolfgang Liebl
Pathogenomic of increased Clostridium difficile virulence
Clostridium difficile is increasingly associated with infections in hospitals and in the community, and hypervirulent types are emerging. Six research groups from 5 countries undertook this project, aiming to use genomic approaches to study C. difficile types with increased virulence and to analyze the presence of known and new virulence factors, regulation of their expression and genomic heterogeneity. The expected results will be valuable for recognizing, monitoring and diagnosing virulent types, improved prevention, and better treatment.
41 Matthias Maass Kamil Önder
Mirja Puolakkainen
Dezso Peter Virok
Johann Bauer
Martha Böttcher
Transcriptome-based Monitoring and Eradication of Chronic Chlamydial Infection - ChlamyTrans -
ChlamyTrans is a consortium of two commercial and four academic partners to study the pathogenomics of chronic Chlamydia infection. Genital Chlamydia trachomatis infection is the leading sexually transmitted disease and Chlamydia pneumoniae is a frequent cause of respiratory infection and linked to atherosclerosis in genetically susceptible individuals. The key for the chlamydial pathobiology is the ability of the pathogen to enter a non-replicative antibiotic-resistant state due to reprogramming of the host cell metabolism. The objective of ChlamyTrans is to use two complementary genome-wide transcriptomics approaches to produce commercially exploitable products for monitoring, treating and ultimately preventing chronic chlamydial infections.
44 Pavel Kovarik Emmanuelle Charpentier
Ilkka Julkunen
Sylvia Knapp
Claire Poyart
Estzter Nagy
Mechanisms and modulation of innate immune responses to Streptococcus pneumoniae and S. pyogenes
Pharmacological modulation of pathogen recognition is a promising, approach to adjust the strength of immune responses. In this project, the recognition of Streptococcus pneumonia and Streptococcus pyogenes by the host innate immune cells will be studied on a whole-genome scale. These bacteria are still a major health concern and are also acquiring widespread resistance to antibiotics. The clinical manifestations of these pathogens are highly variable, partly due to differential recognition of the pathogens by the innate immune system. The project, jointly carried out by 5 academical research groups and one biotech company from 3 countries, will identify novel players in streptococcal diseases and develop strategies leading to modulation of the host's immune response.
45 Thomas Rattei Johannes Hegemann
Romé Voulhoux
Agathe Subtil
Matthias Horn
Jan Rupp
Ana Conesa Cegarra
Host-pathogen protein-protein interactomes and their influence on the host metabolome
Bacterial protein secretion is a key mechanism underlying infection, pathogenesis and modulation of the host cells. In this project, novel biomarkers and drug target candidates will be developed for the diagnosis and therapy of Pseudomonas aeruginosa and Chlamydiae infection. Both pathogens secrete effector proteins into their host cells, and share a high prevalence of infection and disease, limited diagnostics and unspecific therapy. This project benefits from the combined efforts of 7 research groups from 4 countries, and will contribute considerably to the therapeutic efforts targeting these pathogens by developing novel diagnostic strategies and biomarkers and identifying drug target candidates.
49 Stephan Ott
Co-Coordinator: Vítor Martins dos Santos
Manuel Ferrer
Andres Moya
Laya Pedrola
Bernhard Ronacher
Miguel Godinho
Development, prevention and early diagnostic detection of Clostridium difficile-associated pseudomembranous colitis - an interdisciplinary network
Pseudomembranous colitis is an infectious disease of the human colon, mostly caused by Clostridium difficile. A major aetiology of pseudomembranous colitis is the use of broadspectrum antibiotics, which lead to an altered intestinal microflora and to activation or overgrowth of C. difficile. The goal of the project network, comprising 7 research groups from 4 countries, is to characterize the composition and metabolic/functional status of intestinal microflora from the non-diseased stage towards C. difficile-associated pseudomembranous colitis in the human system, thereby enhancing our understanding of this disease and paving the road for the early diagnosis and effective prevention and intervention strategies.
50 Alexander Mellmann Dorothea Orth
Nicolas Barnich
Eduard Torrents
Identification of hot spots of divergence and rapidly changing genes within Shiga toxin-producing Escherichia coli
Identification of hot spots of divergence and rapidly changing genes within Shiga toxinproducing Escherichia coli is the predominant nonpathogenic facultative flora of the human intestine. Some E. coli strains have acquired specific virulence factors, allowing them to cause a broad spectrum of human diseases. This project, which represents a multi-disciplinary collaboration of four research groups from Austria, France , Germany and Spain, will focus on Shiga toxin-producing E. coli (STEC) and on Adherent-Invasive E. coli (AIEC), two intestinal pathogenic subgroups of E. coli. The results of this project will lead to a new understanding of basic principles of pathogenesis, to improvement of diagnosis and typing, and to establishing of new preventive and therapeutic approaches.
 
   
   
   
     
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