MRC Centre for Medical Mycology

Lead Research Organisation: University of Exeter
Department Name: Biosciences

Abstract

The major contribution of fungi to the global burden of disease is not widely appreciated, despite the fact that fungi infect billions of people annually. While most infections are non-life threatening superficial infections, such as athlete's foot, millions of people contract invasive fungal diseases resulting in global mortality figures that rival those of tuberculosis or malaria. Despite their huge burden and high rates of death, fungal infections remain understudied compared with other infectious diseases and there is a pressing need for more research in this field. Experts in the field, including Aberdeen scientists, have identified three priorities that require urgent attention: (i) to improve our ability to detect fungal infections, (ii) to generate better antifungal drugs, and (iii) to enhance the understanding of fungal immunity and its exploitation to fight these diseases. The limited progress in tackling these challenges is due, in large part, to a lack of basic and clinical scientists working in this field in the UK and worldwide.

The UK has a small but highly active community of scientists working on fungal diseases (medical mycologists), with the largest group based at The University of Aberdeen (the Aberdeen Fungal Group, AFG). The AFG, which consists of 11 independent research teams, totalling around eighty individuals, is internationally recognised as a leading group in this field. We aim to achieve maximal synergistic potential within the diverse expertise of the AFG by establishing a world-leading MRC Centre of excellence for research and training in Medical Mycology (MCMM). The MCMM will focus on performing cutting-edge interdisciplinary research and on training the next generation of scientists to increase research capacity in this neglected field in the UK.

Establishing the MCMM will facilitate full integration of the complementary areas of expertise into six exciting research themes that address the key priorities of this field. Moreover, creation of the MCMM will lead to the recruitment of two academics whose expertise will add significant complementary value to the current group, and enable expansion of our research capacity into important new areas. One post will be in Bioinformatics, which will study and help process our massive biological datasets. This post will empower new technologies that will allow us to gain important insights into the mechanisms of fungal disease. The second post will be in immunology which, in addition to delivering cutting-edge science, will help promote the translation of our scientific discoveries into new diagnostic, preventative and therapeutic applications. The MCMM will also be used as a platform to raise awareness and influence policy regarding the management of fungal diseases within the broader academic community and the general public.

A major objective of the MCMM is to increase capacity in medical mycology in the UK by delivering a cohort of 21 basic and clinical researchers through a range of world leading training programmes. This will include a bespoke four-year MRes-PhD programme for 13 students that will provide a broad interdisciplinary training that is not available anywhere else; 3 Early Career Fellowships to promote an early independent research career in medical mycology for outstanding individuals; 5 Fellowships for excellent clinical trainees to provide one year of focussed academic training and research and to establish a foundation for subsequent PhD fellowship applications; and 10 eight-week summer scholarships for fourth-year medical students to stimulate their interest in medical mycology, and to promote links between the MCMM and other centres in this field. The MCMM Fellows, PhD students and clinical trainees will underpin the integration of the AFG, through appointment to jointly-supervised projects within our new research themes, and will significantly advance our understanding of fungal disease.

Technical Summary

We will create an MRC Centre which is recognised internationally as a leading centre of excellence for research and training in Medical Mycology (the MCMM). Creation of the MCMM will enable us to establish an optimal configuration that will exploit our collective strength and will maximise our potential for fundamental and translational science, as well as for providing world-leading training in medical mycology. New posts in bioinformatics and in experimental immunology will add scope, depth and translatability to our existing research strengths. Six innovative and cross-disciplinary research themes are proposed:

1. Fungal cell surface dynamics and its impact on antimicrobial chemotherapy and host immunity;

2. Fungal components as antifungal drug targets, diagnostics, vaccine antigens and adjuvants;

3. Fungal growth, adaptation and morphogenesis in the context of infection;

4. Temporal host-fungal interactions and key mediators that influence disease establishment and progression at molecular, cellular and organismal levels;

5. Exploiting emerging technologies to generate global perspectives that broaden our mechanistic understanding of host-fungal interactions;

6. Unravelling patient susceptibility to enable directed diagnosis, treatment and prevention of fungal disease.

MCMM Early Career Fellows, PhD students and clinical trainees will enable these research themes and foster interconnectivity and interdisciplinarity within and beyond the MCMM. The training of these Fellows and students will address the urgent requirement for increased capacity in basic and clinical research in this neglected field in the UK. Creation of the MMCM will also accelerate translation of our science and promote a vibrant public outreach programme, maximising the impact of the excellent mycology research that occurs in Aberdeen.

Planned Impact

We propose to establish an MRC Centre in Medical Mycology (MCMM), an area of infectious disease that has enormous impact on morbidity and mortality but whose influence on human health is not widely appreciated. Creation of a world-leading centre of excellence for research and training in medical mycology will provide benefit to academia, industry, clinicians and the general public.

Benefits to academia: The training programmes within the MCMM will produce a cohort of basic scientists and clinicians with expertise in medical mycology. This cohort will contribute to building research capacity in this neglected field in the UK, adding vitality to the sector. The training and mentoring of a new cohort of Early Career Fellows will similarly contribute to capacity building in this field. Research projects addressing our new themes will lead to new interdisciplinary collaborations and advance our understanding of fungal disease. The results generated will be of interest to a wide range of specialities including, for example, immunologists and systems biologists as well as clinical academics in several specialities including, for example, infectious disease and dermatology.

Benefits to industry: Research in the MCMM will address the most pressing questions in medical mycology and is very likely to generate exploitable data, tools and resources that will advantage industry. For example, our ongoing and planned research activities will contribute directly to the development of new diagnostic platforms and drug discovery screens. Exploitation of these discoveries will be achieved through our extensive and longstanding links with other universities, SMEs and pharmaceutical companies, and the support of key translational infrastructure that is available at the University of Aberdeen. These activities will be enhanced by our institution's MRC Confidence in Concept and Wellcome Trust ISSF awards.

Benefits to clinicians: In addition to increasing capacity in clinical medical mycology through our training programme, MCMM research has the potential to improve management strategies and patient outcome in the future. In addition to the exploitable discoveries described above, for example, the new insights into antifungal immunity that we will generate may help explain susceptibility to infection and lead to the development of novel immunotherapeutic approaches. As described in the Case for Support, we have already made impacts in such areas.

Benefits to patients and the general public: The creation of the MCMM will help focus national and international attention on this important area of infectious disease. Our research will be of interest to the general public because many individuals suffer from fungal infections, as detailed in our Case for Support. We plan to disseminate information about fungal infections in the scientific and popular press, on the Internet and social media, through live events and our other outreach activities. The MCMM will host open days, continue school outreach activities, and host work experience and placement programmes for undergraduate students. MCMM members will continue to provide guest lectures on medical mycology to basic science and clinical undergraduates and postgraduates at universities throughout the UK, to raise awareness of this field. Moreover, MCMM members will continue to be involved in national patient organizations and to present our research to patients and their relatives. All MCMM staff will be involved in public outreach activities. In the longer term, MCMM research will contribute to improved treatment and outcome, resulting in enhanced quality of life and reduced impact on health care budgets.

Benefits to our Students and Fellows: In addition to world-leading training in medical mycology, the MCMM will actively promote the career development of trainees through close mentoring, training in transferable skills, and the development of strong support networks.

Publications

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