Skip to main content

Metabolomics of fungal diseases: a systems biology approach for biomarkers discovery and therapy

Objective

Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (including fungi) and individual variations in the microbiome influence host health and disease. The fact that fungi are capable of colonizing almost every niche within the human body suggests that they must possess particular immune adaptation mechanisms, the breakdown of which may result in fatal fungal infections and severe fungal diseases. Traditional reductionist approaches of the past have not been sufficient to address these new challenges in the pathogenesis of fungal diseases. Here, I propose an integrated, systems biology approach to understand the role of L-tryptophan (trp) metabolic pathways in multilevel host−fungus interactions. Present in mammals as well as in fungi, pathways of trp metabolic pathways are exploited by the host and the fungal biota for survival and immune adaptation. A variety of indole derivatives, generated through conversion from dietary trp by symbiotic bacteria, activate the aryl hydrocarbon receptor/IL-22 pathway that provides antifungal resistance and tissue repair. Harmful inflammatory responses to fungi are instead tamed by kynurenines generated via the enzyme indoleamine 2,3–dioxygenase (IDO) of the trp pathway. Through high-throughput wet-lab ‘omics’ techniques combined with computational techniques, the project aims at defining the molecular basis of mammalian and fungal IDO activity and a metabolic network linking the metabolic phenotype (metabotype) to immune adaptations and its possible breakdown in experimental and human fungal infections. The project will provide ideal post-graduate training focussed on the development of metabolomics for diagnosis of fungal diseases and optimization of current antifungal therapy and diet that are of relevance to public health care solutions.

Call for proposal

ERC-2011-ADG_20110310
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

UNIVERSITA DEGLI STUDI DI PERUGIA
Address
Piazza Dell Universita 1
06123 Perugia
Italy
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 889 599,20
Principal investigator
Luigina Romani (Prof.)
Administrative Contact
Vincenzo Nicola Talesa (Prof.)

Beneficiaries (3)

UNIVERSITA DEGLI STUDI DI PERUGIA
Italy
EU contribution
€ 1 889 599,20
Address
Piazza Dell Universita 1
06123 Perugia
Activity type
Higher or Secondary Education Establishments
Principal investigator
Luigina Romani (Prof.)
Administrative Contact
Vincenzo Nicola Talesa (Prof.)
UNIVERSITA DEGLI STUDI DI FIRENZE
Italy
EU contribution
€ 337 600,80
Address
Piazza San Marco 4
50121 Florence
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Pierangelo Geppetti (Prof.)
UNIVERSITA DEGLI STUDI DI PARMA
Italy
EU contribution
€ 72 000
Address
Via Universita 12
43100 Parma
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Antonio Mutti (Prof.)