Calcium signaling and cytoskeletal dynamics during polarized hyphal growth and infection by the human fungal pathogen Aspergillus fumigatus

• Applicant: Dr. Constanze Seidel
• Subject Area: Cell Biology ; Microbial Ecology and Applied Microbiology ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250947341

The most common invasive mould infection worldwide is caused by Aspergillus species, and over 90% of all cases are caused by the human pathogen Aspergillus fumigatus. During infection of the human host lung, A. fumigatus responds to the immediate environment via signal transduction cascades, which are conveyed by a network of receptors, non-protein messengers, enzymes and transcription factors. Ca2+, as a second messenger, plays a fundamental role in signaling during the growth and development of all eukaryotic cells and is an evolutionarily conserved, highly versatile intracellular signal molecular. However, surprisingly little is known about Ca2+-signalling during fungal pathogenesis.The overall objective of the current proposal will be to analyse the roles of Ca2+-signaling in regulating polarized hyphal growth and the cytoskeletal dynamics that are required for pathogenicity and successful infection by A. fumigatus. One aim will be to identify proteins that play key roles in Ca2+-signaling during polarized hyphal growth and infection of mammalian epithelial cells. Various Ca2+-channels, -pumps and -antiporters will be localized and analysed to determine the role they play in generating [Ca2+]c-spikes in growing hyphal tips. Whether specific [Ca2+]c-spiking signatures are associated with spatio-temporal developmental processes such as polarized growth and the sensing and infection of epithelial cells, will be investigated. Observing [Ca2+]c, cytoskeletal and motor protein dynamics in hyphae during growth over the surface of an epithelial cell layer will give further insights into their roles during the infection process. These aims will be addressed using cutting edge experimental techniques including: mutant and overexpression analyses; advanced live-cell imaging using confocal and TIRF microscopy; Ca2+-imaging; localization and quantification of key proteins involved in Ca2+-signaling, the cytoskeleton and molecular motors in living cells; and infection assays with mammalian epithelial cells.The overall objective of the proposed study will be to gain fundamentally new insights into the complex roles of Ca2+-signaling in A. fumigatus during polarized growth and pathogenesis. Because of significant differences between the Ca2+-signaling/ homeostatic machinery in fungi compared with that in animals and plants, various components of this machinery have potential in providing novel targets for antifungal drugs in the future.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Nick D. Read