Dr Campbell Gourlay (University of Kent)/Dr Carol Munro (University of Aberdeen)
Project title: Investigating the role of mitochondrial electron transport chain function in fungal pathogenicity and drug resistance”. Supervisors/collaborators
PhD Student: Lucian Duvenage
Start date: 20 September 2014
The world is experiencing a rapid expansion in the number of aged and immune-compromised patients who are classified as at high risk from life threatening invasive fungal infections. There is therefore an increasing requirement for the development of new therapeutic strategies to counter the inevitable emergence of resistant pathogens. In addition there is also the need to train a greater number of scientists able to tackle these problems now and in the future. Our research will greatly increase our knowledge as to how mitochondria, an essential component of most eukaryotic cells, are involved in controlling the ability of two of the most common human fungal pathogens Candida albicans and Candida glabrata to infect and resist common treatment regimes. This will be achieved using cutting edge technologies and world-class supervision available within the Fungal Research Groups placed within the Universities of Kent and Aberdeen. Our investigations will identify new factors that are important for the establishment of fungal infections and so will allow for the development of future life-saving treatment regimes. Crucially this project will also lead to the development of a new and well trained researched specialized in the field of medical mycology.
 Dr Simon Johnston (University of Sheffield)/Professor Robin May (University of Birmingham)
Project title: How do fungal pathogens initiate and modulate localised immune signalling during an infection.
PhD Student: Alfred Kamuyango
Start date: 01 October 2014
When the immune system does not function properly e.g. in cancer, old age and HIV infection (the virus that causes AIDS), we are vulnerable to infections, especially fungi, that normally do not cause disease. One such infection is the fungal pathogen Cryptococcus that causes an estimated 660,000 deaths each year, the vast majority in people with AIDS. The zebrafish represents a unique opportunity to study these interactions as they are transparent in their early life and have an immune system that is similar to our own. We have developed ways to look at zebrafish in three- dimensions over time that mean we can study the individual behavior of many immune cells and microbes during infection. We are also testing large numbers of potential new drugs as well as trying to find new jobs for existing drugs. We believe that using knowledge gained from these experiments we will be able to develop new treatments for these diseases.
 Dr Elaine Bignell (University of Manchester)/Dr Julian Naglik (King’s College London)
Project title: Molecular basis of invasive growth during mould infection of the lung.
PhD Student: Joy Icheoku
Start date: 16 September 2014
Fungal spores are abundant in the air and most life-threatening fungal infections begin with inhalation of a fungal particle. However, the mechanisms by which fungal pathogens penetrate the lining of the lung (also called the epithelium) are unknown. This research will focus upon the fungus causing the highest burden of lung disease world-wide, Aspergillus fumigatus. Recently we discovered an A. fumigatus mutant which is unable to invade the lung epithelium. By observing the interaction of this mutant with human lung cells we found the mutant to be deficient in two distinct, and morphotype-dependent, modes of interaction with the epithelial stratum. The earliest interaction involves actin- and Dectin 1-mediated internalisation of fungal spores, which might provide the impetus for further pathogen-mediated damage. A subsequent interaction involves epithelial decay mediated by secreted fungal proteins. Our key hypothesis is that both host and pathogen activities promote epithelial decay. We now wish to further characterise the molecular basis of the host-pathogen interaction by a) Defining the inflammatory pathways activated in epithelial cells by spore internalisation, germination and hyphal growth and b) identifying the key secreted ‘effectors’ which damage epithelia in mice and man. These studies will enlighten the search for potential vaccine candidates with which to protect against invasive mould infections.
 Professor Lars Erwig and Professor Neil Gow (University of Aberdeen)
Project title: The impact of C-type lectin receptor mediated fungal recognition on phagosome maturation and the outcome of the host-pathogen interaction
PhD Student: Fernanda Alonso
Proposed start date: 01 October 2014
Host defence against fungal infections relies mainly on the ingestion and elimination of fungal cells (a process called phagocytosis) by cells of the innate immune system, especially neutrophils and macrophages. Pattern recognition receptors are the main type of receptors that recognise, bind and ultimately facilitate the uptake of fungal cells. Here we focus on a specific subset of pattern recognition receptors the so called C-type lectin receptors (CLRs) as they have been shown to be essential for anti-fungal immunity. Deficiencies in the function of CLRs in humans result in susceptibility to fungal infections. We have developed novel live cell imaging methodologies which enable us to break down and dissect the phagocytosis process into discrete steps: fungal recognition and binding, engulfment, phagosome maturation and finally death of either the fungus or the phagocyte. We will combine this with bespoke genetic tools to modify both the host and the pathogen. The overall purpose of this approach is to determine the roles of key C-type lectin receptors (CLRs) in the temporal dynamics of phagocytosis and phagosome maturation of fungal cells and ultimately the outcome of fungal infection. These studies will help to identify the suitability of CLRs and downstream receptor pathways as therapeutic targets.