A. fumigatus is the primary etiological agent of invasive aspergillosis, a disease that primarily affects individuals who are immunocompromised, and causes 200k life threatening infections annually. A. fumigatus also causes chronic diseases in the ostensibly immunocompetent population which affects around 3 million individuals and leads to c.400k deaths (http://www.gaffi.org/why/fungal-disease-frequency). About 20 million have lifelong conditions caused by an immune hyperactivity to A. fumigatus. Only three classes of drugs are currently recommended for the treatment of aspergillosis with the azole class being recommended for primary therapeutic purposes. Resistance to the azoles is rapidly emerging and for individuals that are infected with a resistant isolate mortality rates are almost 90%. Our understanding of the mechanisms that lead to resistance to the azoles is somewhat limited and novel agents to treat all forms of Aspergillosis are desperately needed.
We have recently discovered 12 transcriptional regulators that are associated with drug resistance in A. fumigatus. The functional role of many of these factors is unknown. In this project our aim is to use our extensive functional genomics toolkit, including tn-seq (a next generation sequencing approach to identify drug sensitive mutants), to fully characterise these transcriptional regulators, identify transcriptional co-regulators and identify routes to disrupting their function. The outputs of this project will support the development of novel diagnostics to detect antifungal resistance and help in the development of new antifungal drugs.
Training/techniques to be provided:
The student will benefit from a diverse and enriching environment and will be trained in the molecular manipulation and characterisation of the human pathogenic fungus Aspergillus fumigatus, molecular techniques including next generation sequencing and qPCR, in vitro assays including MIC determination, mammalian cell culture and in vivo animal models. These skills will provide the student with a competitive advantage for future professional job applications both to academia and industry.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Genetics
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”
For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk