Community Research and Development Information Service - CORDIS


MitoFun Report Summary

Project ID: 614562
Funded under: FP7-IDEAS-ERC
Country: United Kingdom

Mid-Term Report Summary - MITOFUN (Mitochondria as regulators of fungal virulence)

The overarching objective of MitoFun is to understand the regulation and evolution of virulence in a key human fungal disease, cryptococcosis, and by extension to investigate whether such mechanisms exist in other pathogens.

Our primary achievements on this project thus far are listed below.

1. In collaboration with groups in the USA and elsewhere in the UK, we have used whole-genome sequencing and comparative phenotyping to identify the genomic rearrangements and single-gene changes that underlie the evolution of virulence in hypervirulent strains of Cryptococcus gattii 2,4
2. In collaboration with Dr. Simon Johnston, we have established and validated the zebrafish model for cryptococcosis 3 and used it to identify a novel virulence mechanism in Cryptococci (manuscript in preparation).
3. We have discovered a novel, vesicle-mediated mechanism of hypervirulence in C. gattii, which regulates the Division of Labour phenomenon described in our original proposal (manuscript in preparation)
4. We have characterized an important role for antiviral cytokine signaling in modulating antifungal resistance in host cells (manuscript in preparation)
5. We have developed a large number of fluorescent fungal strains, of use not only to our own research but to the community as a whole. Several of these strains have already been distributed to colleagues in other research groups.

In addition, we have made a number of important advances that were not directly envisaged in the original MitoFun project proposal, but which have emerged via research undertaken on this project. Specifically:

1. We have made significant advances in understanding the mechanism that underlies vomocytosis, a novel, non-lytic expulsive process that releases Cryptococci from host phagocytes (manuscript in preparation)
2. We have developed a novel software algorithm for quantifying intracellular parasitism by fungi in live-cell imaging experiments
3. We have started to characterize the importance of host genetic variation in underlying responses to systemic fungal pathogens.

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United Kingdom
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