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MAP kinase cascades controlling virulence in fungi: from signals to pathogenicity response

Final Activity Report Summary - SIGNALPATH (MAP kinase cascades controlling virulence in fungi: from signals to pathogenicity response)

MAP kinase (MAPK) signalling cascades play essential roles in fungal pathogenesis on plants and humans. The main objective of the SIGNALPATH project was to forward our understanding on how MAPK cascades sense and transduce external signals to trigger cellular responses required for fungal infection. This knowledge will be applied to the identification of novel antifungal targets.

SIGNALPATH addresses three key questions:
[1] What is the nature of the MAPK-activating signals and how do fungal pathogens sense and transduce them to the conserved MAPK modules?
[2] Which are the specific downstream target genes/proteins regulated by different fungal MAPK cascades and how do they contribute to plant and human infection?
[3] To what extent are MAPK cascade components functionally conserved among biologically diverse pathogens and how can these proteins be exploited as novel antifungal targets?

The most significant scientific advances obtained in SIGNALPATH are:
1) Construction of fungal reporter strains to monitor activation of different the MAPK cascades under a variety of conditions, including infection.
2) Establishment of genetic screening systems for discovery of new MAPK pathway components.
3) Identification and mutational analysis of several new components of fungal MAPK cascades, including candidates for the elusive upstream receptors or modulators of MAPK activity.
4) Significant progress in the identification of downstream effector genes and proteins, using both transcriptomics and proteomics. Newly identified effectors include secreted and cell surface proteins. The role in pathogenicity has been determined by gene knockout for a number of these newly identified effectors.
5) Comparative genomic analysis conducted by the young researchers in a network-wide collaboration, producing a previously unparalleled overview of the structural conservation of MAPK cascade components among biologically and phylogenetically diverse fungal pathogens. This collective effort has highlighted a number of key MAPK components that are broadly conserved in fungal plant and human pathogens.

The most significant advances in training and transfer of knowledge are:
1) Creation of a core group of young researchers trained in fungal signalling and pathogenesis. This dynamic and highly interactive group of young scientists (both ESRs and ERs) represents a major advance for the European scientific community working in the field of fungal signalling and pathogenesis.
2) Organisation of 7 residential training courses on key topics in the area of fungal signalling and pathogenesis.
- Genome Analysis and associated Bioinformatics. University of Exeter, UK. 6-11 Sept. 2006.
- Transcriptomics. Bayer CropScience Research Center, Lyon, France. 14-18 May 2007.
- Proteomics. Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany. 10-12 and 14 Dec. 2007.
- Scientific Writing and Presenting Module I. Jena, Germany. 13 Dec. 2007.
- Scientific Writing and Presenting Module II. University of Ljubljana, Slovenia. 6-8 May 2008.
- Yeast as a tool for cell biology and gene function analysis. Carlsberg Research Center, Copenhagen, Denmark. 30 Sept.-2 Oct. 2008.
- Medical Mycology and grant writing workshop. University of Aberdeen, UK. 27-29 April 2009.

The final meeting of the SIGNALPATH project was organised as a top-level scientific meeting on MAPK signalling during Fungal Pathogenesis from October 27-29, 2009, at the Harnack House of the Max-Planck-Society in Berlin. It included 22 internationally recognised leaders in the field of fungal MAPK signalling from Europe, US and Japan, the 10 PIs and 19 young researchers from the SIGNALPATH groups. The ESRs and ERs presented talks on their work performed during the project to the international scientific audience.

The SIGNALPATH network has significantly advanced these European teams in generating a critical mass of genomic data available for all partners and the development of advanced tools for these important fungal pathogen species.