Sensing and integration of signals governing cell polarity and tropism in fungi.. (FUNGIBRAIN)
Cell polarity and directed growth (tropism) are fundamental biological processes. Most fungi are dependent on these processes because they grow as polarised filaments called hyphae, whose growth and development are governed by physical and chemical cues from the environment. Such cues include surface-contact, light, nutrients, mating partners, host organisms, or ‘self' hyphae from within the fungal colony. The capacity to re-orient hyphal tip growth in response to external signals forms the basis of the saprotropic, symbiotic and parasitic lifestyles of fungi. For example, dimorphic transitions and directed hyphal growth are intimately associated with virulence in fungal pathogens. The cellular components that control these morphogenetic decisions therefore play key roles in fungal adaptation to environmental change and the invasion stages of infectious growth. Extensive background work has led to the emerging concept of a "fungal brain", which integrates exogenous and endogenous signals to determine the shape and direction of hyphae, both at the levels of the individual cell and of the fungal colony. However, in spite of the universal importance of these processes, surprisingly little is known about their genetic and cellular bases. FUNGIBRAIN brings together pioneering expertise from fungal model organisms such as baker's yeast, fission yeast and the filamentous yeast Ashbya gossypii, and world-class teams working on filamentous fungi, including important human or plant pathogens (Aspergillus fumigatus, Candida albicans, Fusarium oxysporum and Ustilago maydis). The project integrates genetic, biochemical, biophysical, cell biology and systems biology approaches to define common patterns of signal integration and hyphal tropism. Early evidence suggests that these cellular targets are conserved across a broad range of fungal species and thus will have direct and important applications in antifungal treatments and biotechnology.
1. Establish a detailed understanding of conserved fungal signalling networks that regulate polarized and directed fungal cell growth in a wide range of fungal models and pathogens
2. Identify novel conserved targets for antifungal drug discovery in these signalling networks
3. Develop novel high throughput, live-cell fungal tropism screens of mutant and chemical libraries
4. Develop an outstanding interdisciplinary Training Programme on analyzing, manipulating and inhibiting the polarized growth and tropisms of fungi
1. Interplay between intracellular pH and MAPK signalling in the fungal pathogen Fusarium oxysporum
2. Host plant signals and cell receptors activating chemotropic growth in Fusarium
3. Training of 1 ESR (Tania Fernandes Ribeiro) and 1 ER (Stefania Vitale)
4. Organization of the Final International Meeting on "Signal Responses & Tropisms"
1. Turrà D, El Ghalid M, Rossi F, Di Pietro A (2015) Fungal pathogen uses sex pheromone receptor for chemotropic sensing of host plant signals. Nature 527:521-524.
2. Masachis S, Segorbe D, Turrà D, Leon-Ruiz M, Fürst U, El Ghalid M, Leonard G, Richards TA, Felix G, Di Pietro A (2016) A fungal pathogen secretes plant alkalinizing peptides to increase infection. Nat Microbiol (in press).
3. Turrà D, Di Pietro A (2015) Chemotropic sensing in fungus-plant interactions. Curr Opin Plant Biol 26:135-140.
4. Turrà D, Segorbe D, Di Pietro A (2014) Protein kinases in plant pathogenic fungi: conserved regulators of infection. Annu Rev Phytopathol 52: 267-288.
Extensive background work has led to the emerging concept of a "fungal brain", which integrates exogenous and endogenous signals to determine both the morphogenesis and the direction of growth of fungal cells, at the level of the individual cells and the fungal colony. FUNGIBRAIN will focus on the key components of signalling networks involved in regulating polarized and directed cell growth, which are evolutionarily conserved among fungal pathogens and play crucial roles during the infection process. These signalling networks represent rich and largely untapped sources of new antifungal drug targets and will reveal novel virulence mechanisms, which will be exploited in novel assays for the screening of inhibitors using large compound libraries. The results will have direct and important applications in the discovery of novel antifungal compounds that will be of great importance in medicine, agriculture and biotechnology.
INGENIERIA GENETICA EN HONGOS
Code PAIDI: CVI138
ANTONIO DI PIETRO. Partner.
Universidad de Córdoba
Budget of Andalusian group: € 487.865,40