Cryptococcus neoformans causes life threatening meningitis when inhaled propagules escape the lung and disseminate to the brain. Here, the fungal cells proliferate as budding yeast, where the buildup of cerebral pressure causes headaches, disorientation, and death in 600,000 people each year worldwide. These C. neoformans yeast can take on a novel morphology, called Titans, which are resistant to anti-fungals and can act as a reservoir of infection. Titan cells are very large, apolar, highly polyploidy cells that develop through unknown mechanisms, but which involve the activity of conserved RhoGTPases. We study the role of these proteins in cell morphology, ploidy, and pathogenesis using microscopic, molecular biological and proteomic approaches with the long term aim of identifying drug targets for this important human disease.
Most fungi produce long filaments called hyphae, which navigate and steer as they grow through the environment in search of nutrients. Hyphae play an important role in disease – they identify host penetration sites and enable fungi to root themselves deep in internal tissues. We are studying:
Depending upon the immune status of the individual, Candida albicans can colonise diverse niches in humans such as the mouth, gastrointestinal tract, urogenital tract, blood and internal organs. From the perspective of the fungus, the successful colonisation of these niches depends upon the activation of robust stress responses that help to protect it against host immune defences, and the efficient assimilation of available nutrients. We are integrating genomics with proteomics, molecular and cellular biology and systems biology to determine how the fungus integrates stress adaptation with nutrient assimilation during infection, and how these processes influence the pathogenicity of C. albicans and its resistance to antifungal drug therapies.
Professor Gordon Brown's primary research area is innate immunity, with particular emphasis on C-type lectin receptors and their role in antimicrobial immunity and homeostasis. Much of his earlier work revolved around studying the functions of the C-type lectin Dectin-1, a receptor for beta-glucan carbohydrates that plays a key role in anti-fungal immunity. Dectin-1, and subsequently other C-type lectins, were found to be able to mediate numerous cellular responses, to trigger intracellular signalling through novel pathways, and to moduate and directly induce innate and adaptive immune responses. His current research continues to explore the roles and functions of C-type lectins as wel as their involvement in antifungal immunity.
Professor Erwig’s primary research interest is innate immunity in particular the role of macrophages in the progression and healing of inflammation. His past work has focussed on the consequences of apoptotic cell uptake for phagocyte function and in particular on how the digestion of ingested cells or pathogens is controlled within macrophage phagosomes. His current primary research employs novel live cell imaging and analysis methodology to enable the temporal, spatial and functional analysis of phagocyte-pathogen interactions to be dissected and to exploit this to reveal the dynamics of innate immune interactions with cells of fungal pathogens.
Research in Professor Gow's lab focuses on:
Research in Dr MacCallum’s group focuses on:
Research in Dr Munro's lab combines a number of complimentary, molecular biology, microscopy, biochemistry, systems biology, proteomics and genomics approaches to understand fungal pathobiology and design better therapeutics. Key areas of research include:
Dr Adilia Warris’ primary research area is innate immunity with a particular focus on the host-fungus interaction in specific patient groups. Her work has provided new concepts and hypotheses concerning fungal pathogenesis in patients with Chronic Granulomatous Disease (CGD). Invasive infections by A. nidulans are exclusively seen in patients with this particular primary immunodeficiency disorder and behave more aggressively and are significantly more likely to result in death. The phenotype of A. nidulans with regards to its interaction with CGD phagocytes is clearly different from A. fumigatus being the most common cause of invasive aspergillosis in other susceptible patient groups. The defective immune responses in the patient with Cystic Fibrosis shows commonalities with the CGD host with respect to antifungal effector mechanisms, and these are currently being explored by her group.
In a host, certain trace minerals, such as iron and zinc, are actively withheld from invading microbes in a process called nutritional immunity. Therefore, pathogens must have evolved specialised uptake systems in order to proliferate in their hosts and cause disease. We are using a combination of molecular and cellular biology, together with models of host-pathogen interactions, to dissect the mechanisms of micronutrient assimilation by the major human fungal pathogen, Candida albicans.
The Wellcome Trust has funded a £5.1 million Strategic award in Medical Mycology and Fungal Immunology to members of the Aberdeen Fungal Group. Through this Aberdeen will act as the hub of a pan-UK network of collaborations that will involve many of the major institutions that are invested in this area. It represents the single largest award in this field and is testament to the strength and depth that the College enjoys in this field.
The WTSA will fund a number of international studentships, postdoctoral fellows and clinical PhDs to stimulate cross-disciplinary research and training and to build capacity in this field. Details of the objectives for the award, collaborators, as well as opportunities for new Clinincal PhD positions, a Clinical Readership and a new MRes programme in Aberdeen can be found by following the link below.
The Aberdeen Fungal Group was awarded MRC Centre status in 2016, and the new MRC Centre for Medical Mycology (MRC CMM) at the University of Aberdeen will spearhead innovative research and training to generate knowledge that will improve the diagnosis, prevention and treatment of fungal diseases. The MRC CMM represents a joint £6.5m investment by both the MRC and the University of Aberdeen.
The major objectives of our new Centre are to make major scientific advances in areas of urgent medical need, to translate research discoveries into the clinic and industry, to increase future capacity by training the next generation of basic and clinical mycologists, and to raise public awareness of the significant impact of fungal infections on human health.
Funding is available for Early Career Fellowships, Clinical Fellowships, MRes-PhD Studentships and Medical Student Summer Scholarships. To find out more about the Centre and these funding opportunities please follow the link below.