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  • 1. Report of a joint FSA-MRC scientific workshop Opportunities for synergy between basic immunology and food allergy research
  • 2. Opportunities for synergy between basic immunology and food allergy research Report of a joint FSA-MRC scientific workshop Opportunities for synergy between basic immunology and food allergy research Held on 22nd September 2009 at The Royal Society of Medicine
  • 3. Opportunities for synergy between basic immunology and food allergy research Contents Page Introduction 3 The Workshop 3 Outcomes of the break-out discussions 4 Common themes and areas of concensus 8 Conclusions and way forward 9 Annex 1 Information on the FSA’s Food Allergy & Intolerance Programme (T07) 10 Annex 2 Executive summary of MRC Strategic Review of Human Immunology 12 Annex 3 List of Workshop Participants 19 Annex 4 Workshop Programme 20 1
  • 4. Opportunities for synergy between basic immunology and food allergy research Introduction Food Allergy is a major health issue, with 1-2% of adults and 5-8% of children affected in the UK. There are currently no established primary preventative measures or proven therapies for food allergies and management of the condition relies on avoidance of the relevant allergen(s) coupled with use of rescue medication in the event of a reaction. The Food Standards Agency (FSA) has a long-standing commitment to the funding of food allergy research. This is achieved via a programme of research projects aimed at characterising the underlying causes and mechanisms of food allergy, and providing a basis for the development of sound, evidenced based, policies to enable consumers affected by these conditions to make safe and informed food choices (see information on the FSA’s Food Allergy & Intolerance Programme at Annex 1). The Medical Research Council (MRC) also has interests in allergy as part of its wider investment in basic, clinical and translational research in immunology and disorders of the immune system (see executive summary of MRC Strategic Review of Human Immunology attached as Annex 2). Together, these organisations have a shared commitment to delivering public health and consumer benefits in food allergy through the funding of high quality research focussed on improving our understanding of the causes and mechanisms of food allergic disease. Against this background, and following a recommendation from the independent review panel who evaluated the FSA’s Food Allergy & Intolerance research programme in 2008, the FSA and MRC together convened a Workshop in September 2009. The aim of this Workshop was to bring together leading UK researchers from the fields of immunology and food allergy and to explore opportunities for collaborative research. The expectation was that a closer alignment between basic immunology and food allergy research will deliver important benefits to consumers and for public health by generating more powerful hypothesis driven research proposals that address the significant challenges that food allergy poses. The Workshop Over 50 leading research scientists and clinicians with expertise in food allergy and relevant areas participated in the Workshop which was held at the Royal Society of Medicine, London. In addition, representatives from some of the major UK funders of allergy and immunology research, as well as policy makers were in attendance (see list of Workshop participants at Annex 3). The Workshop programme included several key note presentations that described recent developments and current challenges in food allergy and immunology research (see Workshop Programme at Annex 4). There followed parallel break-out sessions during which participants identified areas of 3
  • 5. Report of a joint FSA-MRC scientific workshop synergy where there exist exciting opportunities to exploit recent advances in our understanding of the cellular and molecular biology of immune function to characterise the mechanisms through which immune and allergic responses to food proteins are initiated and regulated. The Workshop closed with a plenary session that sought to provide a synthesis of the key challenges and opportunities. The latter was delivered by Professor Ian Kimber, who chaired the Workshop in his capacity as external programme advisor to the FSA’s Food Allergy and Intolerance Research Programme. Outcomes of the break-out discussions The break-out sessions led to some stimulating and thought provoking discussions about where the major scientific challenges are in our current understanding of the immunobiology of food allergy, which could be informed by better exploitation of existing and emerging basic immunology know-how. The four break-out groups made a series of recommendations in this regard, as summarised below: Group 1 Recommendations: G There is a need to better understand the immunology of the transition from sensitisation to clinical allergy to food proteins, in particular the immunological transition from just having IgE antibody to having IgE antibody plus clinical allergy, in order to inform intervention and therapeutic strategies. As part of this, the following may be important: N Use of in vivo imaging technology (e.g. carboxyfluorescein succinimidyl ester - CFSE labelling) to monitor lymphocyte proliferation, migration and location and which could help elucidate the roles of cytokines such as IL-4 and IFN-γ. N Re-circulation of T lymphocytes (between blood and tissues via the lymph) should be studied to better understand their role in the developing immune response. N The activities and role of allergen specific T cells could be identified and monitored/tracked using antigen-specific tetramers. N The role of basophils in the transition from sensitisation to allergy has been neglected and warrants further study. More research should be carried out on the expression of major histocompatability complex (MHC) class II antigens on the surface of basophils. 4
  • 6. Opportunities for synergy between basic immunology and food allergy research G There is a need to investigate and understand the common disparity between the skin prick test response to food allergens and the lack of gut response to allergen. Is it about how the allergen is affected by digestion and presentation to the immune system that is important? In addressing this, the following may need to be investigated: N What are the mechanisms controlling the balance between oral tolerance to food allergens and immune reactivity in the gut? N What is the impact of the gut microflora and digestion on immune and allergic responses? N More studies are needed on the de-glycosylation of food antigens as there is potential for this to be a strategy for reducing the allergenicity of foods. G The role of chemokines in food allergy warrants investigation but this must be via hypothesis driven research. Assays which give a broad systems-wide view (eg Luminex), which enable the detection and quantification of multiple cytokines or other biological markers in the blood at one time, could prove useful in this regard. G The role and functioning of macrocytes in the food allergic response is a neglected area of research. Group 2 Recommendations: This Group made recommendations in four areas: G There is a need to better understand why some of us develop food allergy whilst others do not. Consideration needs to be given as to what approaches would be of most value in identifying these factors: N In particular there is a need to understand what the secondary factors are that lead to food allergic disease in sensitised individuals, (IgE antibody being the primary factor) and to determine whether these factors are protective or synergistic in their actions. N There is a need for genetic studies of food allergy applying a systems biology approach (which will require large sample sizes), to identify those at risk and to help identify mechanisms as a basis for future research. In the related field of asthma such studies have led to a paradigm shift in understanding and fuelled further research. G There is a need to better understand what immunological parameters define the food allergic phenotype: 5
  • 7. Report of a joint FSA-MRC scientific workshop N Known examples include allergen specific IgE antibody, basophil degranulation and allergen specific T lymphocyte responses. It is also known that Double Blind Placebo Controlled Food Challenges (DBPCFC’s) are the Gold standard diagnostic method for establishing clinical food allergy. What may be learned from other approaches? G Linked with the above, there is a need to understand how to match the immunology with the multiple phenotypes associated with food allergy (e.g. non- allergic/tolerant, sensitised but not clinically allergic, allergic, resolved allergy). G There is a need to understand how best to study the development of food allergy at an immunological level. This will require elucidation of: N Which immunological parameters need to be measured/tracked. N What life stages are important (certainly paediatrics should be a focus of research, but knowledge of paediatric immunology generally is currently lacking). N The best experimental approach. One approach put forward is the need to study a birth cohort made up of individuals at high and low risk of food allergy and study the immunology of food allergy over time alongside other childhood diseases (such as asthma). Group 3 Recommendations: G The clinical relevance and context of allergic disease is important to consider when researching the immunology of food allergy. G There is a need for a better understanding of the different stages of food allergic disease at an immunological level (sensitisation, clinical allergy/tolerance, resolution). G There is a strong need for a better understanding of basic neonatal immunology, which would inform approaches to elucidating the immunobiological mechanisms involved in the development of food allergy in early life. G Biomarkers of effect for food allergy phenotype should be developed using information obtained from longitudinal studies of food allergy and seeking advice from immunologists about biomarkers being developed in other areas of immunology which may be of relevance. These should be used to understand and better define, at an immunological level, what constitutes oral tolerance versus transient allergy versus desensitisation. Such studies could also be informed by a greater understanding of the genetics of food allergy. G Mechanistic studies are required to shed light on the induction, maintenance, progression, exacerbation and regulation phases of food allergic diseases: 6
  • 8. Opportunities for synergy between basic immunology and food allergy research N As part of this, consideration should be given to the relevance of different types of tissue (e.g. skin/gut). N In order to be able to conduct such studies there is a need to develop new approaches for studying the mechanisms of food allergy. Experiments could be carried out using appropriate mouse models which require further development. G The role of antigen presenting cells (APCs) in food allergic responses should be studied. Consideration needs to be given to how APCs should be assessed and how antigen presentation by the cells should be assessed (both in animal models and in humans). G Research on food allergens themselves, to better understand the factors predicting allergenicity, may also be warranted. G To achieve all of the above, there is a need for scientists with different interests and fields of expertise to work together synergistically. This could be facilitated by: N meetings (such as the present FSA-MRC Workshop) N conferences and workshops N ensuring a broad range of knowledge and expertise (including food allergy expertise) on strategy and funding panels N having funding mechanisms that encourage collaborative studies N recognising the need for pump-priming studies G Information derived from future research studies should be shared widely and freely via information repositories in order to inform and facilitate future research. Group 4 recommendations: G There is a need to understand, at an immunological level, why sensitisation does not always lead to allergic disease. In investigating this, parallels could be drawn with what is known about immune responses to commensal bacteria. G A key issue underpinning the above is that many people have immune responses to proteins, but what we need to understand better is what are the characteristics of allergens that lead to sensitisation and which may lead to disease upon dysregulation of the immune system? As part of this, it should be noted that: N Lessons from studies of gut parasites have been useful but are limited. N There is a need to understand the role of industrial food processing (industrialisation of our diet) in modulating (increasing?) the allergenic properties of foods (for example, via food matrix modification). This warrants further study, as does the study of the indirect effect of the overall diet on allergic disease risk via obesity and metabolic syndromes. 7
  • 9. Report of a joint FSA-MRC scientific workshop G The interactions between allergens and target tissues (e.g. skin, gut) should be further studied and this requires the set up and validation of appropriate tissue cell culture systems. Priority funding should be made available for this. G In the longer term, there should be studies of the epigenetics of food allergy, including investigation into the role of the FoxP3 gene and the influence of folic acid intake on inflammatory responses involved in allergy. G There is a real need for a large scale pregnancy cohort followed through post- partum with bio-banking and tissue analysis for food allergy, but this will require large cohorts and studies need to be functional (incisive) and not associative. G More partnerships should be formed between researchers using human and animal subjects as well as between researchers focussing on lung, gut and skin immunology and between basic and clinical scientists in these areas. Common themes and areas of concensus There were a number of recurring themes and areas of consensus that emerged from the discussions in the break-out groups and the plenary discussion. In particular, there appeared to be strong agreement amongst participants that there are significant and fascinating scientific challenges still to be addressed in the food allergy research arena. Furthermore, it was clear that the ability to address these challenges and further our understanding about the mechanistic bases of food allergy will require research that draws on, and is informed by, recent advances to the science in allied areas of basic immunology research. There was also a clear sense that addressing these challenges via future research proposals/projects will require continued and enhanced collaborations between scientists working in fields such as immunology, dermatology, gastroenterology, genetics, toxicology, biochemistry and of course food allergy, as well as incorporating the expertise of both fundamental and clinical scientists. It was recommended that funding organisations and other influential players should consider what activities or initiatives could be undertaken to both promote and strengthen this type of collaboration in research going forward, and to build partnerships to facilitate such collaborations. There was also a strong consensus amongst the specific recommendations for future research that were put forward by the break-out Groups. Workshop participants agreed that future research funding should be directed towards a number of themes in order to have maximum impact on moving scientific understanding of the immunobiology of food allergic disease forward and, ultimately, informing public health policy and practice. These ‘common’ themes were: G There is a strong need for further research to understand, at the immunological level, why sensitisation to food proteins does not always translate into allergic disease. In particular there is a need to understand what factors, other than IgE antibody, are important. 8
  • 10. Opportunities for synergy between basic immunology and food allergy research G There is a need for further research to understand the immunological events associated with desensitisation to food allergens and the induction of oral tolerance, and more generally to enable us to better define the various phenotypes associated with food allergy which could lead to the identification of targets for immunotherapy and inform clinical practice. G There are potentially important tissue differences in immune and allergic responses to food allergens (e.g. an individual can be tolerant in the gut but react on skin). We need to understand differences in specific organ/tissue immunology and how these operate in the context of the development, progression, exacerbation and regulation phases of food allergic disease. G Greater investment in neonatal and paediatric immunology research would be beneficial, and could significantly inform future research on the immunology of food allergy during early life, ideally employing a prospective longitudinal design and a systems biology approach, including the genomics of food allergy. G There continues to be a need to better understand what makes a certain food proteins allergenic, the impact of food processing on allergenicity, and whether allergenicity operates at the level of dendritic cells or epithelial surfaces. G Future research should shift away from associative studies and be strongly hypothesis driven. G There is a need to develop new in vitro and in vivo methods to model food allergy (as opposed to sensitivity). Conclusions and way forward The Workshop was considered to have been a very useful opportunity to initiate discussion between immunologists and food allergy scientists about what the major scientific challenges are currently in food allergy research and where closer alignment between these fields might benefit future research in this area. Clear recommendations emerged from the Workshop and there was a general consensus regarding the key opportunities. The value of building strong links between different areas of research relevant to food allergy was emphasised. It is now the responsibility of funding organisations, such as the MRC and the FSA, to consider the recommendations deriving from the Workshop and and how these can best be addressed. 9
  • 11. Report of a joint FSA-MRC scientific workshop Annex 1 Food Standards Agency’s - Food Allergy and Intolerance Research Programme (T07) The Food Allergy & Intolerance Research Programme funds around £1million/year of fundamental applied clinical and social research on different aspects of food allergy and intolerance to address identified policy needs. The programme was originally set up in 1994 by the Ministry of Agriculture Fisheries and Food (MAFF), with the primary aim of investigating the causes and mechanisms of severe food allergy, in order to reduce the incidence and severity. The Programme has evolved significantly since its inception with studies initially commissioned to focus on the characterisation of peanut and tree nut allergens and on the later stages of allergic disease when sensitisation has already occurred and developed into clinical allergy. More recently the Programme’s focus has shifted to investigate to what extent the prevalence of food allergy is increasing, particularly in children and to peanuts. Following on from this, the Programme has also sought to identify factors that might influence the development of sensitisation to food allergens and to identify those at risk of developing food allergy. Most recently the Programme has commissioned research focusing on increasing our understanding of how the early infant environment and, in particular dietary and other routes of exposure, might influence or promote the acquisition of sensitisation or immunological tolerance to allergenic foods. In many of our studies we have been investigating the underlying mechanisms of the development of food allergy in order to provide evidence to support advice to those affected. The main aims of the Programme were updated in 2007 and are: G To identify the risk factors (e.g. genetic, environmental, dietary and other) associated with the development of sensitisation to food proteins and the development of clinical food allergy, particularly in the early life stages of the individual. Knowledge of these factors and how they influence the development of sensitisation and allergy will enable us to develop appropriate advice for consumers to reduce the risk of development of food allergy. G To investigate the immunological mechanisms of food allergy to understand, at the immunological level, what factors are important in determining/regulating the allergic verses tolerant status. 10
  • 12. Opportunities for synergy between basic immunology and food allergy research G To determine the prevalence of food allergy (both total food allergy and the prevalence of allergy to individual foods) in the UK in infants, children and adults, and whether prevalence is changing over time. G To develop the best research approach and methods to investigate whether there is any association between intolerance to certain foods and children’s behaviour. G To develop suitable methods for the detection of allergens in food. G To determine what factors influence the severity of allergic reactions to food. We have, in February 2008, undertaken an independent critical review of the research programme, to evaluate the success and productivity of the work commissioned and to consider the future focus of the Programme. The outcomes of this review are detailed in the review report which is available from the Agency’s website at: The review discussions identified a number of areas which, along with the current aims, will form the focus of the T07 programme for the next 5 years and assist in the prioritisation of research going forward. These are detailed here below: G Commission further research on the importance of environmental (including dermal) exposure to allergenic foods as a route of sensitisation, building on previous Agency funded research in this area. G Commission research to underpin work on deriving management thresholds for allergenic foods. G Engage with other stakeholder activities both nationally and internationally as appropriate and consider commissioning research to improve the reliability of methodologies for the detection and quantification of food allergens in food products. G Host a scientific workshop to identify and prioritise what further basic immunology work needs to be conducted on food allergy, and issue future research calls in this area as appropriate. 11
  • 13. Opportunities for synergy between basic immunology and food allergy research Annex 2 MRC Strategic Review of Human Immunology Report of the Strategic Review Panel following their meetings on 17 and 18 October and 29 November 2007 Executive Summary 12
  • 14. Report of a joint FSA-MRC scientific workshop 1 Executive summary The purpose of this Strategic Review is to identify significant opportunities and gaps in the field of human immunology research; to examine the MRC’s impact in human immunology research; and the contributions of the MRC’s extra- and intramural investment now and in the future. The Strategic Review Panel was chaired by Professor Herb Sewell, University of Nottingham and a member of the MRC’s Council. The panel included broad human immunology expertise, the MRC’s Infections and Immunity Board (IIB) members, experts from academia and industry and corporate MRC Head Office representation. The first meeting was held on 17/18 October followed by a final meeting on 29 November. Although the findings and recommendations are from the panel itself, we gratefully acknowledge the inputs of a number of national and international experts, universities, Health Departments and other stakeholders. Status of the field For the purpose of the review, the field of human immunology research was broken down in to allergy, autoimmunity, cancer, infectious disease and transplantation. We discussed the current strengths and weaknesses in these fields; levels of funding; and future opportunities. From these discussions, we identified a number of gaps in scientific knowledge, most of which cut across all of these fields. Knowledge gaps in human immunology research The field of innate immunity has recently acquired a new direction and momentum. The US is moving ahead quickly whereas Europe has been slower to respond to new opportunities. Patchy and poorly connected research activity in this area could form the basis for a new capacity building initiative. Included in this must be a strong basic science component but also links to clinical research and access to human tissues and cells. Close interactions with the biotechnology and pharmaceutical industries are also essential in order for better understanding of innate immunity to inform the development of new therapeutics. Inflammation as a subject in itself is vast in scope, much of which extends beyond this review. Greater insight into gene/environmental interactions is yielding new information on the origins and persistence of chronic inflammatory disorders. Our understanding of the basis of chronic inflammation and how the immune, inflammatory and structural cells interact in chronic disease needs to improve. The factors that localise or limit an inflammatory response are still unclear. Also, a major field that deserves more attention is wound healing and the mechanisms involved in fibrosis. For the UK to maintain its competitive edge in this field, greater collaboration across disciplines and between centres, as well as new ways of working with industry are urgently needed. 13
  • 15. Opportunities for synergy between basic immunology and food allergy research Immune cell subtypes: B cells are crucial in human immunology as antigen- presenting and effector cells. Despite the existence of a small number of outstanding groups working on B cell biology in the UK, there is insufficient critical mass in this area. T cells are central to immune processes and disease. Animal models have yielded a lot of important information about their development and function but more research is needed to evaluate how these responses translate to the human situation. Again, to take the field forward, a critical mass of research excellence needs to be developed. Vaccines both preventative vaccination and therapeutic vaccination against chronic viral infection and non-communicable disease needs further investment to realise their considerable potential. Vaccines could also be used to protect from epidemic zoonotic infections. Novel vaccine technologies such as DNA vaccines, peptide vaccines and nanoparticle carriers are all exciting new avenues worth exploring. A greater understanding of innate immunity would improve novel adjuvants and mucosal vaccines and there should also be more imaginative use of vaccines as experimental tools. Understanding the local immune response is an essential first step in allowing us to alter it. We need to understand the interactions at the point of contact between antigens and the immune system as this will ultimately dictate the progression of disease. Access to high-quality human tissue samples from established clinics and greater use of improved imaging technology will be of huge benefit in this area. A greater understanding of the life-course of the immune system in health and disease is crucial in developing new treatments for immune-mediated diseases. The field of early life and foetal immune development has been neglected and research is needed in this area. Paediatric immunology, particularly the development of the immune system in neonates and in infants in relation to infections, vaccines and allergens warrants further study. Research on age-related immune decline will become more important as our population becomes an increasingly aged one. Understanding the life-course of immune diseases will unravel how early immune events dictate disease chronicity. The roles of the chronic inflammatory response; tissue injury and repair; and development of autoimmunity all need to be addressed to further our understanding of disease chronicity. Longitudinal studies of disease and therapy are essential to give us a better understanding of how the disease itself changes. A greater understanding of the determinants of disease process and outcomes is needed. Understanding the genetic basis for immune disease is still in its infancy; identification of novel genes and their functions needs to be improved, embracing a multidisciplinary approach. Greater advantage should be taken of birth cohort studies and other collections for DNA-based studies, epigenetics and connecting epigenetic mechanisms with environmental epidemiology. 14
  • 16. Report of a joint FSA-MRC scientific workshop Addressing disease complexity to understand disease processes and phenotypes would then identify a range of new targets closer to the origins of the disease and potential new treatments. Biomarkers could lead to the earlier identification of disease, give a more informative readout of disease progression and indicate positive outcomes after treatments - increased activity in this area in addition to previous MRC calls would be welcomed. New technologies and tools Animal models can be valuable tools in the study of human immunology but we need more sophisticated animal models that better inform the human system, for example, humanised mouse models and better models of tumour development. Some creative studies in larger mammals to address chronicity of immune diseases are now emerging and these should be further encouraged. Although success in the development of intelligently designed animal models should limit the need for primate research, it is likely that ethics committees would still require pre-clinical data from primates for some studies and this needs to be delivered. In vitro models and techniques should be improved and used alongside novel animal models. For example 3D in vitro models and in silico techniques could be used to model the interaction of immune cells and to study the interaction of cell receptors and their ligands. There also needs to be greater access to high-quality human tissue from established banks and clinics. Imaging is widely accepted to hold huge potential for human immunology research. Advances in imaging techniques now enable us to look at all levels of immune function from molecular and intracellular level right up to high resolution whole body imaging. Greater access to existing and improved facilities will benefit the human immunology community. Structural biology is strong in the UK with a number of groups working in this area. Embedding structural biology, cell biology and immunology in the same environment would have a very large impact on the development of structure-based drug design and on the analysis of structure-activity relationships. There is also tremendous potential for structural genomics and for post-genomic biomedical research. Translating our knowledge of human immunology in health and disease is essential to develop new treatments and therapies. Experimental medicine studies, small-scale studies looking at ‘first-in-human’ experiments, are essential as proof-of-concept for many treatments. Experimental medicine studies will be instrumental in identifying and establishing novel biomarkers of disease and correlates of protection of various treatments. These studies may also be of benefit in areas where animal models are lacking such as immunity in ageing. 15
  • 17. Opportunities for synergy between basic immunology and food allergy research Cohorts should be better used with further establishment of different cohorts to study large populations in health and disease. It is essential that they have long-term support to provide the necessary infrastructure and management required to extract as much information as possible. Long-term support is essential to allow cohorts to look longitudinally at many issues, for example, the long-term consequences of immune manipulation. We can use established tools in novel ways to study the human immune system. For example, vaccination to study immune responses – there are very few studies looking at the short, medium and long-term immune responses after vaccine delivery. Primary genetic immunodeficiencies could also be used as models to investigate immune function. Genome sequencing and genome-wide association studies are expanding our understanding of the genetic components of diseases. Following the identification of genes involved in disease processes, we will also need to identify the gene products and mechanisms downstream. Huge advances in genome sequencing have allowed rapid sequencing of entire genomes making ‘personalised-medicine’ a realistic prospect. The fields of epigenetics, gene constellations, gene silencing, histone acetylation and microRNAs in understanding gene/environmental interactions are in their infancy and require more investment. Developing a ‘systems medicine approach’ will allow us to integrate all levels of information derived from new technologies and tools. This will require input from a range of disciplines including but not exclusively basic scientists, clinicians, modellers and computational biologists. The models produced should be consistent with the experimental medicine approaches so that they respond to changes in phenotype and treatments and so can be further refined. Improved bioinformatics will be needed to translate the vast amount of novel data generated into knowledge. It will be essential to include bioinformatics and information management in any future systems approach and long-term strategy. A roadmap Having identified key gaps and ways to address them, we now present a ‘roadmap’ on how to implement them. We have set out a number of proposals that are key milestones in creating a clear and distinctive roadmap to realise our scientific vision and strategy. Creating an interdisciplinary environment will be essential to take human immunology research forward. Specialists need to work side by side in an interactive multidisciplinary environment as opposed to ‘generalists’ in the lab. The most successful examples of interdisciplinary working are led by individuals with the drive to 16
  • 18. Report of a joint FSA-MRC scientific workshop create this environment. The MRC should attract the right people to new posts. In order to translate research from lab to the clinic and also the other way, there needs to be easier iteration at the basic/clinical interface. Building capacity is a recurring theme throughout this report. Immunology research needs strengthening particularly in the disciplines of paediatrics, geriatrics and global health as well as the core disciplines mentioned above. There is also a serious lack of clinical academics to fulfil the translational research agenda. Also, basic scientists should be encouraged to undertake some clinical training. Building and retaining capacity in basic research is also essential. The MRC should consider using four-year PhD schemes to increase young scientists’ exposure to a range of labs and, in addition to the response mode schemes, establishing a ‘doctoral training account’ for established centres to train new clinical academics. Sustainability of research activity also needs to be maintained. We recommend that the MRC, in partnership with universities, make some key leadership appointments in strategic areas, not only to boost capacity but to stimulate new research in that area. Increasing connectivity will deliver multi-disciplinarity and build capacity but is dependent on creating sustainable partnerships between institutions and sectors. We need to create and increase partnerships between universities, the industrial sector and the Health Departments to take human immunology forward. Partnering with the industrial sector will improve the translation of basic research. Researchers in industry are keen to work in partnership with public sector academics. These relationships should be based on a strong match of interests together with clear, mutually beneficial agreements, agreed in advance by all partners. Product development is high-risk but the risks can be partially mitigated by high-quality proof- of-concept studies such as the MRC’s new experimental medicine initiatives. These present excellent opportunities for industry and academia to collaborate. Industry could also make products available to academics for testing in new experimental and clinical models – allowing new avenues to be explored with much smaller risks. There should also be a greater exchange of personnel between academia and industry for example, through training or joint appointments. Partnering with the Health Departments to integrate UK health research strategy is now the mission of the Office for the Strategic Coordination of Health Research (OSCHR). Their aim is to facilitate more efficient translation of health research into health and economic benefits in the UK through better coordination of health research and more coherent funding arrangements to support translation. The new structures under this arrangement offer significant opportunities to develop clinical immunology, engage with industry and ensure increased translational research whilst maintaining 17
  • 19. Opportunities for synergy between basic immunology and food allergy research basic research. The NIHR Biomedical Research Centres will be instrumental in increasing connectivity between basic and translational research. Also, the NHS is an under-used resource and we recommend that research be incorporated into the reality of NHS life and that the immunology community engages with the Health Departments on how best to achieve this. The NHS is the point of delivery for vaccines in the UK and so can also play a role in long-term vaccine research and immunity studies. Cross-disciplinarity will be important to engage the NHS and DH. Human immunology is naturally cross- disciplinary and the role of the ‘clinical immunologist’ will be critical to help break into the ‘organ-based’ nature of the NHS. How can the MRC deliver in the short, medium and long-term? In the short-term, new funding opportunities offered by a favourable comprehensive spending review settlement will offer new opportunities for human immunology. It is essential to continue response mode funding but there also needs to be some focus and selectivity introduced to achieve strategic impact. To promote new partnerships and increase connectivity, an immunology network should be established. The size and shape of this network needs consideration but there are already some examples that human immunology could follow. Multi-institution/sector consortia are also a strong route for bringing together diverse expertise to tackle challenging research problems. Regulation is a major issue for anyone conducting clinical research. In major centres, the MRC should provide funding for managers with experience of regulatory issues to work with anybody wanting to conduct such research. For those not in the major centres, collaboration with these managers could then be encouraged. Medium-term objectives are to attract and recruit new individuals to neglected research areas; better integrate ‘human’ and ‘mouse’ immunology; and increase capacity. This will require significant funding but the MRC should not ‘over-prescribe’. The universities should be encouraged to approach MRC with their own plans. However, there is also the need to look at mechanisms for funding long-term, large- scale support for human immunology. Units and centres are the current mechanisms for this and both have advantages and disadvantages. Whatever the mechanism, for these to succeed in the human immunology field, they should be closely integrated into universities with associated medical schools and be highly interdisciplinary. The long-term vision would be the implementation of this ‘strategy’ as a whole. The completion of the new UK Centre for Medical Research and Innovation (CMRI) is an exciting future opportunity for long-term human immunology research. 18
  • 20. Report of a joint FSA-MRC scientific workshop Annex 3 List of Workshop Participants Dr Steve Anderton University of Edinburgh Dr Robert Boyle Imperial College London Dr Joelle Buck Food Standards Agency Professor Ben Chain University College London Dr Chun-Han Chan Food Standards Agency Dr Andrew Clark Addenbrookes Hospital Professor Maggie Dallman Imperial College London Professor Dan Davis Imperial College London Dr Rebecca Dearman University of Manchester Professor Graham Devereux University of Aberdeen Dr Anthony Frew Brighton and Hove NHS Trust Professor Paul Garside University of Strathclyde Professor Gerry Graham Glasgow University, MRC IIB Board Member Professor Richard Grencis Manchester University Mrs Sue Hattersley Food Standards Agency Professor Adrian Hayday Kings College London Dr Lesley Heppell BBSRC Miss Ruth Hodgson Food Standards Agency Professor Eric Jenkinson MRC Centre for Immune Regulation, Birmingham Professor Ian Kimber University of Manchester, T07 Programme Advisor Ms Verity Kirkpatrick Food Standards Agency Professor Gideon Lack Kings College London Dr Jane Lucas University of Southampton Dr Martin Penagos Kings College, London Professor Claudio Nicoletti Institute of Food Research Dr Graham Ogg Human Immunology Unit, Oxford Professor Fiona Powrie Oxford University Dr Graham Roberts University of Southampton Dr Isabel Skypala Royal Brompton Hospital Dr Jessica Strid Kings College London Dr Stephen Till National Heart and Lung Institute Dr Victor Turcanu Kings College London Dr Des Walsh Medical Research Council Dr Alisdair Wotherspoon Food Standards Agency Professor David Wraith University of Bristol, MRC IIB Board Member Dr Ann Ager Cardiff University Professor John Warner Imperial College London 19
  • 21. Opportunities for synergy between basic immunology and food allergy research Annex 4 Opportunities For Synergy Between Basic Immunology And Food Allergy Research 22nd September 2009 Wimpole Room at the Royal Society of Medicine 10.00 - 10.30 Registration 10.30 - 10.40 Chair’s introduction and welcome Prof I Kimber University of Manchester 10.40 - 11.00 An introduction to challenges for Prof I Kimber research into the immunology of University of Manchester food allergy. Session 1 : Current challenges in understanding the immunology of food allergy 11.00 - 11.25 Key challenges in food allergy research Prof G Lack currently and the need to understand Guy’s and St Thomas’ the immunology of food allergy. Hospital, London 11.25 - 11.35 Questions 11.35 - 12.00 The role of dendritic cells in Prof C Nicoletti food allergy. IFR 12.00 - 12.10 Questions 12.10 - 12.35 Understanding the allergenicity Dr Rebecca Dearman of proteins : a role for immunotoxicology. University of Manchester 12.35 - 12.45 Questions 12.45 - 1.30 Lunch 20
  • 22. Report of a joint FSA-MRC scientific workshop Session 2: Emerging topics in immunology 1.30 - 1.55 Title to be confirmed :The role of T-cells Prof Fiona Powrie and their products in immunoregulatory Oxford University mechanisms in the gut in the context of inflammatory bowel disease. 1.55 - 2.05 Questions 2.05 - 2.30 Lymphoid Stress-Surveillance by Prof Adrian Hayday Unconventional T cells. Kings College London 2.30 - 2.40 Questions 2.40 - 3.05 An overview of novel imaging techniques Prof Paul Garside that could be applied to food University of Strathclyde allergy research. 3.05 - 3.15 Questions 3.15 - 3.30 Coffee Break Session 3: Reflection on the presentations and Discussion of areas of synergy 3.30 - 4.00 Syndicate group brain storming session Group Chairs: Dr Graham Roberts, Dr Andrew Clark, Prof. Adrian Hayday, Prof. Paul Garside 4.00 - 4.45 Open discussion of areas of synergy Chair: Prof I Kimber between the two fields of research 4.45 - 4.55 Summary Prof I Kimber 4.55 - 5.00 Closing remarks Close 21
  • 23. © Crown copyright Published by Food Standards Agency March 2010 FSA/1560/0310