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Fungal pathogenicity emerging through functional adaptations to host environments

Project description

Decoding what makes fungi deadly

Fungal infections are a serious global threat: invasive Candida infections kill around 40 % of those affected. While related non-pathogenic species exist, scientists still do not fully understand what makes some fungi deadly and others harmless. The ERC-funded FungalPath project aims to uncover the molecular roots of fungal pathogenicity. Specifically, it will combine molecular profiling using advanced mass spectrometry with high-throughput phenotyping to compare diverse yeast pathogens with their non-pathogenic relatives. The researchers will study and simulate how fungi adapt and how they interact with the human body, identifying traits and metabolic adaptations that distinguish pathogenic from harmless species. This will provide insights that could improve infection control, guide treatments and help predict the emergence of new fungal threats.

Objective

Fungal infections pose a serious medical threat, especially when they invade the bloodstream. The most common cause of fungal bloodstream infections is invasive candidemia, primarily attributed to a small group of pathogens, including Candida albicans, Nakaseomyces glabratus, Candida tropicalis, and Candida parapsilosis. Such infections are associated with crude mortality rates nearing 40%. Increasing numbers of very closely related yet non-pathogenic species have been sequenced and identified. However, a functional understanding of what differentiates them from their pathogenic counterparts is lacking. As fungal pathogenicity is a multifactorial trait that is influenced by intrinsic and extrinsic factors, it is hard to explain directly from genomic data. This proposal aims to address these challenges by integrating molecular data with physiological contexts across a broad set of species with varying pathogenicity. By leveraging recent advances in mass spectrometry-based analytics that allow for large-scale molecular profiling of both microbial pathogens and human biofluids, combined with high-throughput methods for deep phenotyping of microbial isolates, and by using and identifying scalable yet physiologically relevant growth conditions and infection-relevant phenotypes, we aim to (1) identify adaptations required for pathogenicity and their molecular basis; (2) identify infection-relevant phenotypes and metabolic differences that distinguish pathogenic from non-pathogenic species; and (3) obtain a quantitative understanding of host-pathogen physiology and their interactions. Thus, we aim to uncover traits, phenotypes, and conditions that enable and intersect with pathogenicity. These breakthroughs will be critical for managing and combating these life-threatening infections and predicting the future emergence of human fungal pathogens.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2025-STG

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Host institution

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Net EU contribution
€ 1 478 047,00
Address
Chariteplatz 1
10117 Berlin
Germany
Region
Berlin Berlin Berlin
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 478 047,00

Beneficiaries (1)