The genetics and epigenetics underpinning a broad spectrum of human fungal pathogens (360G-Wellcome-215239_Z_19_Z)

£97,523

Fungal pathogens are a global threat to human health. Few antifungal drugs are effective, and even these are becoming less useful as fungi increasingly develop resistance. New treatments and mitigation efforts are hampered by the lack of basic science on the genetic basis of virulence in these pathogens. I will address this, by describing how pathogenic fungi regulate gene expression by genetic and epigenetic means in cell culture vs. ex vivo (macrophages). I will further characterize and verify regulatory networks, changes to nucleosome positions and histone modifications in response to macrophages. Foci may include the cell membrane component ergosterol, which is an important antifungal drug target, as well as capsule genes that are essential virulence factors in some pathogens. By comparing across multiple pathogen systems, I will identify the extent genomic instability provides a mechanism for adaptation, how gene expression correlates with the host environment and what role chromatin state plays in virulence. Understanding the molecular mechanisms that drive the evolution of these phenotypic determinants will enable the development of new remedial measures.

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Grant Details

Amount Awarded 97523
Applicant Surname Farrer
Approval Committee Science Seeds Advisory Panel
Award Date 2018-11-02T00:00:00+00:00
Financial Year 2018/19
Grant Programme: Title Seed Award in Science
Internal ID 215239/Z/19/Z
Lead Applicant Dr Rhys Farrer
Partnership Value 97523
Planned Dates: End Date 2022-06-30T00:00:00+00:00
Planned Dates: Start Date 2020-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South West