BMS Research Grants of up to £10,000 are available to fund fungal biology research-related activities at different levels, from small equipment or lab consumables to pump-priming a new research direction. Read about recently awarded grants below.
Research Grants are competitive and are awarded annually; applications must be received by the end of March.
Grants awarded in 2024
Investigating the role of epigenetic mechanisms in antifungal adaptive responses
Antifungal resistance (AFR) is a growing problem that poses a significant threat to global human health. Resistance to the very limited available set of antifungal drugs is emerging worldwide and poses a significant challenge in the clinical management of invasive fungal infections, which kill over 3.7 million people annually. Beyond genetic adaptation mechanisms, emerging data has begun to show the vital roles of “epigenetic mechanisms” in the emergence of AFR. However, our understanding of epigenetics in human fungal pathogens is very limited and the role of epigenetic mechanisms in AFR largely remains unexplored.
The aim of this research project is to investigate the role of epigenetic mechanisms in antifungal adaptive response using A. fumigatus as a model system. To achieve this, I will carry out systematic profiling of epigenetic factor knockout (EPKO) mutants in their antifungal adaptive responses. The key objectives of this proposal are: (i)To determine key epigenetic modifications driving antifungal susceptibility and cell heterogeneity involving antifungal tolerance; (ii) To identify epigenetic factors responsible for antifungal priming response (iii) To characterise the impact of EPKO in the adaptive evolution of antifungal resistance and its clinical implications.
Domestication of clinical isolates of human fungal pathogens
Fungal infection is currently very difficult to diagnose, and mortality rates are far higher than almost all other infectious diseases. However, the effectiveness of the drugs used to treat infection is reducing as antifungal drug resistance has emerged. Candida albicans and Candida glabrata rank first and second respectively as the most common fungal pathogens of humans. The incidence of infection has grown rapidly over the last 20 years with the reason for this increasing incidence not fully understood but these species have a high intrinsic tolerance to antifungals.
In a laboratory setting the primary media used to grow yeast strains is YPD (Yeast dextrose, Peptone, Glucose). For the microbes this environment is extremely cozy: there is an abundance of high-quality nutrients and little competition from neighbouring microbes. My hypothesis is that by growing clinical isolates on YPD, we are losing critical information on the genetic and phenotypic traits associated with the emergence of drug resistance. To address this hypothesis, I aim to answer two questions: (i) What is the rate of domestication of clinical isolates in the presence of YPD? (ii) which single nucleotide polymorphismss related to drug resistance are lost first, returning the clinical isolates to a new baseline state similar to that of laboratory strains?
Grants awarded in 2023
Fungal ageing as a driver of antimicrobial resistance in Candida species
Fluconazole-resistant Candida glabrata isolates are increasing in the clinical setting and Candida auris is an emerging multidrug-resistant yeast. Pilot data shows that replicatively aged (RAGE) or old C. albicans cells are more tolerant to clinically relevant antifungal drugs when compared to young C. albicans. I predict that RAGE cells within mixed cultures of other fungal species will also be tolerant to antifungals. I will use the “track and trace” methodology to identify whether C. auris and C. glabrata RAGE subpopulations persist following antifungal treatment with azoles and echinocandins. These experiments will provide valuable insight into the pathways that contribute to the enhanced antifungal resistance exhibited by old C. albicans cells, and whether aging influences antifungal drug resistance in other important fungal pathogens. Such information will provide a springboard for this start up project in my lab to secure future longer-term funding.
Internal transcribed spacer (ITS) primer evaluation for fungal metabarcoding in soils
Fungi are the dominant soil eukaryotes performing crucial ecosystem functions. Next Generation Sequencing has expanded our ability to characterise fungi and their ecological roles, and molecular ecologists typically use part or all of the internal transcribed spacer (ITS) region to assess fungal community composition and diversity. There is a lack of consensus about which portion of the ITS region should be targeted, and what primers achieve the greatest taxonomic coverage. Studies evaluating different ITS primers have been limited, targeting bioaerosols, or only investigating single soil type (e.g. temperate soil). We will conduct a new review of different ITS primers across multiple soil types to assess which primers, or combinations, are required to fully capture fungal biodiversity. Results wil be published as a guide for ITS-based metabarcoding studies and projects targeting soil fungal communities.
Pathogenic fungi in Alzheimer’s disease: can Cryptococcus neoformans infection potentiate neuroinflammation in murine models of Alzheimer’s Disease?
Alzheimer’s disease (AD) is a devastating neurodegenerative disease affecting >50 million people at a global economic cost of >$1 trillion. Risk of developing AD depends on both genetic and environmental factors. Microbial infection is a likely trigger for AD by initiating central nervous system inflammation and production of pathological proteins. Of the microbes that could initiate AD, neurotropic pathogens abundant in the environment are the best candidates: >80% of humans are exposed to the neurotropic fungus Cryptococcus in their lifetime. Our project will: ascertain whether AD is associated with the presence of fungi in the central nervous system; determine whether cryptococcosis affects expression of AD-associated risk genes and mediators of neuroinflammation. We aim to establish key pilot data to support follow-on proposals for dissecting whether neurotropic fungal infection can trigger or potentiate AD and related neurodegeneration, which will create an exciting research avenue.
Biotechnological application of fungal expression systems for the heterologous production of invertebrate neurotoxins
Many animals produce venom with neurotoxic activity via the modulation of neuronal ion channels. These venoms are produced as a mixture of hundreds of different peptides causing severe toxic effects. However, individual peptides show a high specificity by targeting selected subtypes of receptors and ion channels, making them highly attractive for pain therapy, as a cure for epilepsy and cancer, or as insecticides. Despite the great potential of these peptides for pharmaceutical applications, their characterisation and utilisation are severely hampered by the cumbersome isolation and low yield from natural sources.
Filamentous fungi have an inherent ability to secrete proteins for solubilisation of nutrients, and the protein secretory pathway has been well studied. This project focuses on the exploitation of protein secretion by filamentous fungi for venom peptide production. If successful, the system will be used for the systematic expression, purification, and characterisation of neurotoxins with an emphasis on the characterisation of spider and centipede toxins for their application in pain therapy.
Grants awarded in 2022
Spore-specific mechanisms of Cryptococcus pathogenicity
Cryptococcus neoformans is an invasive fungal pathogen that causes over 200,000 deaths a year. Cryptococcal disease occurs by dissemination of the pathogen from the lung into the brain and, importantly, can ensue years after exposure. However, the mechanisms of Cryptococcus dissemination and intracellular latency are still unclear. Margherita’s study aims to investigate the interaction of Cryptococcus spores with Airway Epithelial Cells (AECs), the frontline cells in the respiratory tract, with a view to understanding the mechanisms by which spores contribute to Cryptococcus latency, dissemination and ultimately pathogenesis.
Mycotoxin presence in plant-based diets across the UK: survey and assessment
Plant-based lifestyles have grown significantly in recent years. Currently, 19% of the UK population classify themselves as vegetarians or vegans and the current trends point out an increase in the near future. However, a plant-based diet can increase the exposure to chemical contaminants such as mycotoxins. The long-term objective is to study the exposure of these sub-populations in-depth and improve risk communication and management approaches for this niche of ever-growing tendencies in plant-based diets. Esther’s study will enable the research group to generate preliminary data, supporting the creation of a long-term relationship with all major vegetarian and vegan associations and charities in the UK.
The simultaneous use of arbuscular mycorrhizal fungi and cyanobacteria to improve wheat productivity
With the urgent need to sustainably feed an increasing human population, attention is turned into using microbial inoculants to reduce the need for chemical fertilisers in agricultural systems. Among these, arbuscular mycorrhizal fungi (AMF), and Nostoc, a genus of cyanobacteria with nitrogen-fixing abilities, are two promising avenues. Sandra’s study will test the hypothesis that the dual application of AMF and cyanobacteria improves wheat growth to a greater extent than when each organism is introduced alone or compared to no introduction at all.