A genome scale census of virulence factors in the major mould pathogen of human lungs, Aspergillus fumigatus

Lead Research Organisation: University of Manchester
Department Name: School of Biological Sciences


Infectious diseases caused by fungi are a worldwide problem causing as many deaths as malaria and tuberculosis. Azole drugs are the only orally available anti-mould agents and resistance to these drugs is increasing, possibly due to their use as agricultural fungicides. There is therefore a desperate need to develop new antifungal treatments. The major fungal pathogen in the air we breathe is called I and people affected by cancer, or requiring organ transplants, are at risk of fatal infections caused by it. We do not fully understand how A. fumigtaus survives inside the lung and urgently need more basic information about this pathogen so we can begin to design future therapies. By asking which transcription factors (TFs) control the ability of A. fumigatus to cause disease, we can achieve a global view of the regulatory network which drives infection. We have created a genome-scale collection of 401 A. fumigatus bar-coded mutants, each lacking a single TF. We will now use murine infection models with the mutant library and a state of the art DNA sequencing technology, to test the virulence of all TF mutants simultaneously. To identify the genes which are regulated by pathogenicity TFs we will use ChIP-Seq analysis and transcriptome profiling (RNA-Seq). Computational analyses of these datasets will reveal the regulatory network driving pathogenicity in A. fumigatus and lead us directly to the fungal processes we need to target with new drugs.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011208/1 30/09/2015 29/09/2023
1640253 Studentship BB/M011208/1 30/09/2015 29/09/2019 Norman Van Rhijn
Description Fungal regulators required for causing Aspergillus fumigatus infections have been identified from a panel of 484 transcription factors. The cohort required for infection correlates with regulators required for serum and temperature tolerance, potentially highlighting the evolutionary nature of this pathogen.
Exploitation Route The evolutionary nature of Aspergillus fumigatus pathogenicity and regulators required for infection can be further investigated.
Sectors Education,Healthcare,Pharmaceuticals and Medical Biotechnology

Description Killer Fungus 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Academics from Manchester Fungal Infection Group and Aberdeen Fungal Group created an event, Killer Fungus, as part of Manchester Science Festival. This generated awareness for fungal infections in an accessible manner for children of all age and parents.
Year(s) Of Engagement Activity 2017
URL http://www.killerfungus.org