PhD Drug repurposing for the treatment of aspergillosis

About the Project

The mould Aspergillus fumigatus was classified by the WHO as a critical priority pathogen in 2022. It causes a spectrum of invasive, allergic and chronic disease. It results in high mortality in the immunocompromised and causes a significant symptom burden in those with chronic lung disease. However, there are only three classes of drugs with meaningful activity against Aspergillus: the azoles, the echinocandins and the polyene Amphotericin B. The rate of resistance to the azoles, the only available oral agent, is increasing both in the environment and during treatment in patients, severely limiting our options to treat this fungus.

As newer agents may not reach the market soon, repurposing of existing drugs should be considered. After screening an FDA library of drugs for synergy with the antifungal voriconazole, we found the statins to be the most promising agents. Before embarking on clinical trials, real-world clinical data should be analysed to explore the potential for repurposing of existing drugs to treat aspergillosis. This project will aim to

a.      Identify suitable agents for drug repurposing in aspergillosis

b.      Explore the effect of statins, agents shown to have antifungal properties in vitro, on outcomes of patients with diagnosed aspergillosis syndromes. This will be done by analysing primary care data through an existing research database.

c.      Explore the role of concomitant medications on outcomes of patients treated with antifungals. This will be done by analysing a large patient population with chronic pulmonary aspergillosis treated at a national referral centre.

Eligibility

Candidates are expected to hold (or be about to obtain) a minimum upper second-class honours degree (or equivalent) in Data Science, Biological Sciences or a related area / subject. Masters degree in biostatistics is desirable.

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 application form please select PhD Medical Mycology

For international students, we offer the opportunity for you to undertake an accredited teaching certificate whilst carrying out your research with our PhD with Integrated Teaching Certificate. We also offer self-funded international students the chance to study a master’s before progressing onto a PhD with our Integrated PhD. Visit our international postgraduate researchers page to find out more.

Equality, Diversity & 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

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website View Website

References

van Rhijn N, Storer I, Birch M, Oliver J, Bottery M, Bromley M (2023) The novel agrochemical fungicide ipflufenoquin drives cross-resistance to olorofim in the human pathogen Aspergillus fumigatus. Research Square preprint DOI: 10.21203/rs.3.rs-2621591/v1

Braeckel… Kosmidis C. et al. (2022) Treatment outcome definitions in chronic pulmonary aspergillosis: a CPAnet consensus statement. European Respiratory Journal. DOI: 10.1183/13993003.02950-2021

Kosmidis C. et al (2020) Isavuconazole therapeutic drug monitoring during long-term treatment for chronic pulmonary aspergillosis. AAC. DOI: 10.1128/AAC.01511-20

Bongomin F, Harris C, Hayes G, Kosmidis C, Denning DW (2018) Twelve-month clinical outcomes of 206 patients with chronic pulmonary aspergillosis. PloS one. DOI: 10.1371/journal.pone.0193732