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In-host adaptation in chronic fungal airway infections and development of new antifungals

Timeline

Starting in 2020

Group and collaboration

Dr. Hans de Cock – Molecular Microbiology, Institute of Environmental Biology, UU and Dr. Seino Jongkees – Molecular Pharmacy, Utrecht Institute for Pharmaceutical Sciences, UU

PhD student: -

Project description

This project focuses on the development of new antifungals. Aspergillosis is a lung associated Aspergillus fumigatus infection, which can lead to chronic infection in people with cystic fribrosis, resulting in decreased respiratory function. The resistance of Aspergillus fumigatus strains to antifungal agents is increasing and above all there are few antifungal agents available. In dogs it has already been demonstrated that the fungus adapts in dogs by accumulating mutations and there are also indications that such adaptations occur in human patients. "To effectively treat patients in the future we need to understand the adaptation of Af in airways of CF patients and to develop new antifungals.”

Task

  1. Selection and typing CF isolates
  2. Characterisation phenotypes of CF isolates
  3. Genomic and SNP analysis
  4. SNP-based mutants of CEA10 and FI model tests
  5. Development AO FI model with Af293/CEA10
  6. Comparison of subset CF isolates in FI models
  7. Cloning and expression of trehalase
  8. Synthesis and selection of trehalase inhibitors
  9. Screening peptide-based antifungals oCelloScope
  10. Screening peptide-based antifungal

Disease Intervention Strategies is the overarching theme for more than 10 PhD tracks in NCOH projects to create new interdisciplinary, inter-thematic, and inter-institutional research collaborations.