Exeter academics awarded grants for pioneering fungal research

Dr Carolina Coelho and Dr Liliane Mukaremera

Two scientists from the The MRC Centre for Medical Mycology, based at the University of Exeter, have received prestigious Springboard Awards from The Academy of Medical Sciences for their research into a deadly fungal disease.

Biomedical researchers Dr Liliane Mukaremera and Dr Carolina Coelho will both use the funding to support their investigations into the fungal pathogen Cryptococcus neoformans.

Meningitis caused by the pathogen kills many people with weakened immunity, such as those with cancer, organ transplant recipients and HIV/AIDS. In HIV/AIDS patients alone, this meningitis kills over 181,000 people each year even with antifungal treatment.

Therefore, there is an urgent need to better understand the fungal pathogen causing the disease in order to develop new drugs.

Dr Liliane Mukaremera’s project will determine how the cell wall changes in the presence of drugs used to treat patients suffering from Cryptococcus Meningitis.

Cryptococcus has a shield made of two layers; the capsule and the cell wall, which protects it from harsh environmental conditions and the immune system.

Many studies have focused on the role of the capsule in Cryptococcus infections while the knowledge about the cell wall has fallen behind, despite it being a major target for the treatment of other fungal infections.

Dr Mukaremera will compare the cell wall composition of Cryptococcus cells grown in the laboratory with and without antifungal drugs, and Cryptococcus cells isolated directly from patients before treatment and 7 days into treatment.

She will also identify how genes responsible for cell wall components are controlled in the presence of these antifungal drugs. The cell wall is absent in human cells, and therefore is a great target for antifungal drug development

“I am delighted to receive the Academy of Medical Sciences Springboard Award” said Dr Mukaremera.

“This award will allow me to investigate the impact of the cell wall plasticity on the pathogenesis of the fungal pathogen Cryptococcus neoformans and antifungal drug resistance.

“As an African scientist, this Springboard award will allow me to work both in Uganda and Exeter, and establish important collaborative networks between Africa (Kampala, Uganda) and the UK (University of Exeter).

“This will support my ambitions to broaden my research to other fungal diseases endemic to Africa in the future.”

Dr Carolina Coelho will use her award to investigate how Cryptococcus neoformans can invade the brain so quickly.

Cryptococcus neoformans kills by infecting the human lungs (pneumonia) and brain (meningitis). However, it is not clear how the fungusinvades the human body, or how it travels from the lungs via the air we inhale, into the bloodstream, to reach the human brain. Dr Coelho recently discovered that Cryptococcus can transit from the lungs to the brain extremely quickly (within hours).

Dr Coelho will map exactly when and where this fungus reaches the brain using state-of-the-art microscopy and imaging technologies to visualise the fungus in the act of invasion.

She will then identify key components used by Cryptococcus to bind and damage our tissues in the critically-invaded sites.

Together, these two objectives will greatly enhance knowledge of fungal invasion – a critical step in the progression of this deadly disease – with a view to developing better methods of prevention, such as novel drugs or vaccines.

“I am very excited and honoured to accept the Academy of Medical Sciences Springboard Award” said Dr Coelho.

“This grant will be used to study the dynamics of brain invasion by my “favourite” human fungal pathogen, Cryptococcus neoformans.

“I will have help from my fabulous team of collaborators, in Exeter and abroad, and I hope this will be the start of beautiful discoveries.

“I will be hiring someone with experience in cell culture, mouse models of infection, microscopy and molecular biology, so stay tuned. “

Springboard offers a bespoke package of support to biomedical researchers at the start of their first independent post to help launch their research careers. This includes funding of up to £100,000 over two years and access to the Academy’s acclaimed mentoring and career development programme.

See the full list of awardees here: https://acmedsci.ac.uk/grants-and-schemes/grant-schemes/springboard/springboard-awardees

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