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Interaction of fungal pathogens with host cells: a post-genomic approach

Final Activity Report Summary - GALAR FUNGAIL II (Interaction of fungal pathogens with host cells: a post-genomic approach)

Fungal infections have a significant impact upon the health of the European population. Candida albicans is the most common cause of life-threatening fungal infections, the frequency of which is rising with the numbers of intensive care patients and elderly citizens and many systemic Candida infections are fatal. An in-depth understanding of the molecular events involved in the interplay between fungal pathogens and the host should provide the knowledge base for the development of novel diagnostic and therapeutic approaches that will result in a better management of Candida infections. In this context, the aims of the Galar Fungail 2 Research Training Network (GF2) were to develop an innovative research program on several facets of Candida-host interactions while providing high-quality training to young scientists who will be at the centre of research on fungal infections in the future.

Through the research program conducted between 2004 and 2007, major progress has been made in deciphering molecular events involved in the interplay between C. albicans and the host. These advances were possible thanks to post-genomics tools that provided the necessary environment to investigate the biology of the pathogen and the host in depth.

Major advances include:
- A deeper understanding of signalling networks that regulate C. albicans virulence attributes, especially the ability to switch from the yeast to hyphal growth forms and to adapt to various stresses. Novel regulators of morphogenesis have been identified. The structure, specificities and targets of signalling networks have been defined, providing tools to monitor their behaviour during host-pathogen interactions. For instance, single cell profiling has enabled to study C. albicans responses to oxidative stress during interactions with host cells ex vivo and in vivo.
- An exceptionally detailed description of the C. albicans cell wall (CW) architecture using a combination of biochemical and genetic approaches. Novel CW analytical procedures have provided a handle on the CW proteome that was, for instance, shown to be exquisitely sensitive to changes in ambient oxygen concentration and iron availability. This has been complemented by the characterisation of a large panel of C. albicans mutants with defects in CW proteins, providing the first example of CW regulatory proteases associated with virulence of pathogenic fungi.
- Pioneering studies to obtain the first detailed in vivo transcriptional profiles of C. albicans and host cells during infection of mice and patients and from infection models. This approach has shed new light on both fungal and host biological processes and the delicate interplay between host and pathogen, has identified novel infection-associated genes, and has had an ethical benefit by reducing reliance on animal experimentation.
- Novel host components have been identified that control the establishment of systemic infections and host cell invasion. Also, vaccination approaches to prevent C. albicans infections have been uncovered.

Six PhD students and five post-doctoral fellows have been directly involved in the research program of the GF2 Training Network. In addition to the state-of-the-art research training that these GF2 researchers received, they benefited from two other main types of training. The GF2 Network provided an outstanding balance of interdisciplinary research training courses that covered topics in fungal molecular and cell biology, immunology and genomics. The courses combined hands-on practical work with lectures and tutorials from leading scientists in the field. In addition, the GF2 Network provided a comprehensive set of training courses on transferable skills. This invaluable combination of high-quality research training and training in transferable skills will facilitate the career progression of our researchers.