Dissecting innate immunity to airborne opportunistic fungi through a genome-wide screen in Drosophila

Objective

In recent years, airborne filamentous fungi have become major causes of life-threatening infections in an expanding population of severely immunocompromised individuals. Aspergillus remains the most common fungal pathogen in these patients, whereas Zygomycetes are emerging causes of fatal invasive fungal infections in many cancer institutions. Overall, the increasing frequency and spectrum of invasive fungal infections and the alarming rates of resistance to antifungal agents in fungi underscores the need to expand our knowledge on the immunopathogenesis of opportunistic fungal infections and develop novel therapeutic strategies. Importantly, the versatility of virulence mechanisms of fungi and the complexity of host defense mechanisms against fungi highlights the importance of understanding the molecular aspects of host-fungal interplay in robust experimental systems.
Over the past decade, invertebrate mini-host models with well-characterized genetics and less complex immunity have been effectively used to explore several aspects of both fungal pathogenicity and antifungal host defense. These properties coupled with the robust genetics in Drosophila, make flies an ideal model to study the molecular aspects of host-fungal interaction.
We have recently implemented Drosophila melanogaster as a model to study virulence mechanisms and the molecular aspects of host immune response to Zygomycetes. Surprisingly, we found that key aspects of the pathophysiology of zygomycosis in humans were appropriately modeled in fruit flies.
In this proposal we expand on our previous work to:
(a) Identify novel genes involved in Drosophila immunity against the most important airborne opportunistic fungi, Aspergillus and Zygomycetes, by performing a genome-wide screening strategy in Drosophila RNAi lines.
(b) Confirm in humans the functional role of novel Drosophila host defense genes by silencing the relevant homologues in human phagocytic cells

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• medical and health sciences basic medicine physiology pathophysiology
• medical and health sciences health sciences infectious diseases
• natural sciences biological sciences microbiology mycology
• medical and health sciences basic medicine immunology
• medical and health sciences clinical medicine oncology

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2010-RG
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IRG - International Re-integration Grants (IRG)

Coordinator