Report of a joint FSA-MRC scientific workshop

Report of a joint FSA-MRC scientificworkshop

Opportunities for synergy between basic

immunology and food allergy research

Opportunities for synergy between basic immunology and food allergy research

Report of a joint FSA-MRC scientificworkshop

Opportunities for synergy between basic

immunology and food allergy research

Held on 22nd September 2009 at

The Royal Society of Medicine

Contents

PageIntroduction 3

The Workshop 3

Outcomes of the break-out discussions 4

Common themes and areas of concensus 8

Conclusions and way forward 9

Annex 1Information on the FSA’s Food Allergy & Intolerance Programme (T07) 10

Annex 2Executive summary of MRC Strategic Review of Human Immunology 12

Annex 3List of Workshop Participants 19

Annex 4Workshop Programme 20


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IntroductionFood Allergy is a major health issue, with 1-2% of adults and 5-8% of children affectedin the UK. There are currently no established primary preventative measures or proventherapies for food allergies and management of the condition relies on avoidance of therelevant 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 offood allergy research. This is achieved via a programme of research projects aimed atcharacterising the underlying causes and mechanisms of food allergy, and providing abasis for the development of sound, evidenced based, policies to enable consumersaffected by these conditions to make safe and informed food choices (see informationon the FSA’s Food Allergy & Intolerance Programme at Annex 1). The Medical ResearchCouncil (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 asAnnex 2). Together, these organisations have a shared commitment to deliveringpublic health and consumer benefits in food allergy through the funding of highquality research focussed on improving our understanding of the causes andmechanisms of food allergic disease.

Against this background, and following a recommendation from the independentreview panel who evaluated the FSA’s Food Allergy & Intolerance research programmein 2008, the FSA and MRC together convened a Workshop in September 2009. Theaim of this Workshop was to bring together leading UK researchers from the fields ofimmunology and food allergy and to explore opportunities for collaborative research.The expectation was that a closer alignment between basic immunology and foodallergy research will deliver important benefits to consumers and for public health bygenerating more powerful hypothesis driven research proposals that address thesignificant challenges that food allergy poses.

The Workshop

Over 50 leading research scientists and clinicians with expertise in food allergy andrelevant areas participated in the Workshop which was held at the Royal Society ofMedicine, London. In addition, representatives from some of the major UK funders ofallergy and immunology research, as well as policy makers were in attendance (see listof Workshop participants at Annex 3). The Workshop programme included several keynote presentations that described recent developments and current challenges in foodallergy and immunology research (see Workshop Programme at Annex 4). Therefollowed parallel break-out sessions during which participants identified areas of


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Report of a joint FSA-MRC scientific workshop

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synergy where there exist exciting opportunities to exploit recent advances in ourunderstanding of the cellular and molecular biology of immune function tocharacterise the mechanisms through which immune and allergic responses to foodproteins are initiated and regulated.

The Workshop closed with a plenary session that sought to provide a synthesis of thekey challenges and opportunities. The latter was delivered by Professor Ian Kimber, whochaired the Workshop in his capacity as external programme advisor to the FSA’s FoodAllergy and Intolerance Research Programme.

Outcomes of the break-out discussions

The break-out sessions led to some stimulating and thought provoking discussionsabout where the major scientific challenges are in our current understanding of theimmunobiology of food allergy, which could be informed by better exploitation ofexisting and emerging basic immunology know-how. The four break-out groups madea series of recommendations in this regard, as summarised below:

Group 1 Recommendations:

� There is a need to better understand the immunology of the transition fromsensitisation to clinical allergy to food proteins, in particular the immunologicaltransition from just having IgE antibody to having IgE antibody plus clinical allergy,in order to inform intervention and therapeutic strategies. As part of this, thefollowing may be important:

� � 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.�

�� 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.

�� The activities and role of allergen specific T cells could be identified and monitored/tracked using antigen-specific tetramers.

�� 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 antigenson the surface of basophils.

� There is a need to investigate and understand the common disparity between theskin 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 theimmune system that is important? In addressing this, the following may need to beinvestigated:

�� What are the mechanisms controlling the balance between oral tolerance to food allergens and immune reactivity in the gut?

�� What is the impact of the gut microflora and digestion on immune and allergic responses?

�� 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.

� The role of chemokines in food allergy warrants investigation but this must be viahypothesis driven research. Assays which give a broad systems-wide view (egLuminex), which enable the detection and quantification of multiple cytokines orother biological markers in the blood at one time, could prove useful in this regard.

� The role and functioning of macrocytes in the food allergic response is a neglectedarea of research.


This Group made recommendations in four areas:

� There is a need to better understand why some of us develop food allergy whilstothers do not. Consideration needs to be given as to what approaches would be ofmost value in identifying these factors:

�� 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.

�� 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.

� There is a need to better understand what immunological parameters define thefood allergic phenotype:


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�� 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?

� Linked with the above, there is a need to understand how to match theimmunology with the multiple phenotypes associated with food allergy (e.g. non-allergic/tolerant, sensitised but not clinically allergic, allergic, resolved allergy).

� There is a need to understand how best to study the development of food allergyat an immunological level. This will require elucidation of:

�� Which immunological parameters need to be measured/tracked.

�� What life stages are important (certainly paediatrics should be a focus of research, but knowledge of paediatric immunology generally is currently lacking).

�� 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).


� The clinical relevance and context of allergic disease is important to consider whenresearching the immunology of food allergy.

� There is a need for a better understanding of the different stages of food allergicdisease at an immunological level (sensitisation, clinical allergy/tolerance, resolution).

� There is a strong need for a better understanding of basic neonatal immunology,which would inform approaches to elucidating the immunobiological mechanismsinvolved in the development of food allergy in early life.

� Biomarkers of effect for food allergy phenotype should be developed usinginformation obtained from longitudinal studies of food allergy and seeking advicefrom immunologists about biomarkers being developed in other areas ofimmunology which may be of relevance. These should be used to understand andbetter define, at an immunological level, what constitutes oral tolerance versustransient allergy versus desensitisation. Such studies could also be informed by agreater understanding of the genetics of food allergy.

� Mechanistic studies are required to shed light on the induction, maintenance,progression, exacerbation and regulation phases of food allergic diseases:

�� As part of this, consideration should be given to the relevance of different types of tissue (e.g. skin/gut).

�� 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.

� 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 antigenpresentation by the cells should be assessed (both in animal models and in humans).

� Research on food allergens themselves, to better understand the factors predictingallergenicity, may also be warranted.

� To achieve all of the above, there is a need for scientists with different interests andfields of expertise to work together synergistically. This could be facilitated by:

�� meetings (such as the present FSA-MRC Workshop)

�� conferences and workshops

�� ensuring a broad range of knowledge and expertise (including food allergy expertise) on strategy and funding panels

�� having funding mechanisms that encourage collaborative studies

�� recognising the need for pump-priming studies

� Information derived from future research studies should be shared widely and freelyvia information repositories in order to inform and facilitate future research.

Group 4 recommendations:

� There is a need to understand, at an immunological level, why sensitisation doesnot always lead to allergic disease. In investigating this, parallels could be drawnwith what is known about immune responses to commensal bacteria.

� A key issue underpinning the above is that many people have immune responses toproteins, but what we need to understand better is what are the characteristics ofallergens that lead to sensitisation and which may lead to disease upondysregulation of the immune system? As part of this, it should be noted that:

�� Lessons from studies of gut parasites have been useful but are limited.

�� 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.


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� The interactions between allergens and target tissues (e.g. skin, gut) should befurther studied and this requires the set up and validation of appropriate tissue cellculture systems. Priority funding should be made available for this.

� 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 folicacid intake on inflammatory responses involved in allergy.

� 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 requirelarge cohorts and studies need to be functional (incisive) and not associative.

� More partnerships should be formed between researchers using human and animalsubjects as well as between researchers focussing on lung, gut and skinimmunology 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 fromthe discussions in the break-out groups and the plenary discussion. In particular, thereappeared to be strong agreement amongst participants that there are significant andfascinating 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 ourunderstanding about the mechanistic bases of food allergy will require research thatdraws on, and is informed by, recent advances to the science in allied areas of basicimmunology research.

There was also a clear sense that addressing these challenges via future researchproposals/projects will require continued and enhanced collaborations between scientistsworking in fields such as immunology, dermatology, gastroenterology, genetics,toxicology, biochemistry and of course food allergy, as well as incorporating the expertiseof both fundamental and clinical scientists. It was recommended that fundingorganisations and other influential players should consider what activities or initiativescould be undertaken to both promote and strengthen this type of collaboration inresearch going forward, and to build partnerships to facilitate such collaborations.

There was also a strong consensus amongst the specific recommendations for futureresearch that were put forward by the break-out Groups. Workshop participants agreedthat future research funding should be directed towards a number of themes in orderto have maximum impact on moving scientific understanding of the immunobiology offood allergic disease forward and, ultimately, informing public health policy andpractice. These ‘common’ themes were:

� There is a strong need for further research to understand, at the immunologicallevel, why sensitisation to food proteins does not always translate into allergicdisease. In particular there is a need to understand what factors, other than IgEantibody, are important.

� There is a need for further research to understand the immunological eventsassociated with desensitisation to food allergens and the induction of oraltolerance, and more generally to enable us to better define the various phenotypesassociated with food allergy which could lead to the identification of targets forimmunotherapy and inform clinical practice.

� There are potentially important tissue differences in immune and allergic responsesto 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 howthese operate in the context of the development, progression, exacerbation andregulation phases of food allergic disease.

� Greater investment in neonatal and paediatric immunology research would bebeneficial, and could significantly inform future research on the immunology offood allergy during early life, ideally employing a prospective longitudinal designand a systems biology approach, including the genomics of food allergy.

� There continues to be a need to better understand what makes a certain foodproteins allergenic, the impact of food processing on allergenicity, and whetherallergenicity operates at the level of dendritic cells or epithelial surfaces.

� Future research should shift away from associative studies and be stronglyhypothesis driven.

� 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 initiatediscussion between immunologists and food allergy scientists about what the majorscientific challenges are currently in food allergy research and where closer alignmentbetween these fields might benefit future research in this area. Clear recommendationsemerged from the Workshop and there was a general consensus regarding the keyopportunities. The value of building strong links between different areas of researchrelevant to food allergy was emphasised.

It is now the responsibility of funding organisations, such as the MRC and the FSA, toconsider the recommendations deriving from the Workshop and and how these canbest be addressed.


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Annex 1

Food Standards Agency’s - Food Allergy and Intolerance Research Programme (T07)

The Food Allergy & Intolerance Research Programme funds around £1million/year offundamental applied clinical and social research on different aspects of food allergyand intolerance to address identified policy needs. The programme was originally setup in 1994 by the Ministry of Agriculture Fisheries and Food (MAFF), with the primaryaim of investigating the causes and mechanisms of severe food allergy, in order toreduce the incidence and severity.

The Programme has evolved significantly since its inception with studies initiallycommissioned to focus on the characterisation of peanut and tree nut allergens andon the later stages of allergic disease when sensitisation has already occurred anddeveloped into clinical allergy. More recently the Programme’s focus has shifted toinvestigate to what extent the prevalence of food allergy is increasing, particularly inchildren and to peanuts. Following on from this, the Programme has also sought toidentify factors that might influence the development of sensitisation to food allergensand to identify those at risk of developing food allergy. Most recently the Programmehas commissioned research focusing on increasing our understanding of how the earlyinfant environment and, in particular dietary and other routes of exposure, mightinfluence or promote the acquisition of sensitisation or immunological tolerance toallergenic foods. In many of our studies we have been investigating the underlyingmechanisms of the development of food allergy in order to provide evidence tosupport advice to those affected.

The main aims of the Programme were updated in 2007 and are:

� To identify the risk factors (e.g. genetic, environmental, dietary and other)associated with the development of sensitisation to food proteins and thedevelopment of clinical food allergy, particularly in the early life stages of theindividual. Knowledge of these factors and how they influence the development ofsensitisation and allergy will enable us to develop appropriate advice for consumersto reduce the risk of development of food allergy.

� To investigate the immunological mechanisms of food allergy to understand, at theimmunological level, what factors are important in determining/regulating theallergic verses tolerant status.

� To determine the prevalence of food allergy (both total food allergy and theprevalence of allergy to individual foods) in the UK in infants, children and adults,and whether prevalence is changing over time.

� To develop the best research approach and methods to investigate whether there isany association between intolerance to certain foods and children’s behaviour.

� To develop suitable methods for the detection of allergens in food.

� To determine what factors influence the severity of allergic reactions to food.

We have, in February 2008, undertaken an independent critical review of the researchprogramme, to evaluate the success and productivity of the work commissioned andto consider the future focus of the Programme. The outcomes of this review aredetailed in the review report which is available from the Agency’s website at:food.gov.uk/multimedia/pdfs/t07review2008.pdf

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 theprioritisation of research going forward. These are detailed here below:

� Commission further research on the importance of environmental (includingdermal) exposure to allergenic foods as a route of sensitisation, building on previousAgency funded research in this area.

� Commission research to underpin work on deriving management thresholds forallergenic foods.

� Engage with other stakeholder activities both nationally and internationally asappropriate and consider commissioning research to improve the reliability of methodologies for the detection and quantification of food allergens in food products.

� Host a scientific workshop to identify and prioritise what further basic immunologywork needs to be conducted on food allergy, and issue future research calls in thisarea as appropriate.


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Annex 2

MRC Strategic Review of Human Immunology

Report of the Strategic Review Panel following theirmeetings on 17 and 18 October and 29 November 2007

Executive Summary


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1 Executive summary The purpose of this Strategic Review is to identify significant opportunities and gaps inthe field of human immunology research; to examine the MRC’s impact in humanimmunology research; and the contributions of the MRC’s extra- and intramuralinvestment now and in the future. The Strategic Review Panel was chaired by ProfessorHerb Sewell, University of Nottingham and a member of the MRC’s Council. The panelincluded broad human immunology expertise, the MRC’s Infections and ImmunityBoard (IIB) members, experts from academia and industry and corporate MRC HeadOffice representation. The first meeting was held on 17/18 October followed by a finalmeeting on 29 November. Although the findings and recommendations are from thepanel itself, we gratefully acknowledge the inputs of a number of national andinternational experts, universities, Health Departments and other stakeholders.

Status of the field

For the purpose of the review, the field of human immunology research was brokendown in to allergy, autoimmunity, cancer, infectious disease and transplantation. Wediscussed the current strengths and weaknesses in these fields; levels of funding; andfuture opportunities. From these discussions, we identified a number of gaps inscientific 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 newopportunities. Patchy and poorly connected research activity in this area could formthe basis for a new capacity building initiative. Included in this must be a strong basicscience component but also links to clinical research and access to human tissues andcells. Close interactions with the biotechnology and pharmaceutical industries are alsoessential in order for better understanding of innate immunity to inform thedevelopment of new therapeutics.

Inflammation as a subject in itself is vast in scope, much of which extends beyondthis review. Greater insight into gene/environmental interactions is yielding newinformation on the origins and persistence of chronic inflammatory disorders. Ourunderstanding of the basis of chronic inflammation and how the immune,inflammatory and structural cells interact in chronic disease needs to improve. Thefactors that localise or limit an inflammatory response are still unclear. Also, a majorfield that deserves more attention is wound healing and the mechanisms involved infibrosis. For the UK to maintain its competitive edge in this field, greater collaborationacross disciplines and between centres, as well as new ways of working with industryare urgently needed.

Immune cell subtypes: B cells are crucial in human immunology as antigen-presenting and effector cells. Despite the existence of a small number of outstandinggroups 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 lotof important information about their development and function but more research isneeded to evaluate how these responses translate to the human situation. Again, totake the field forward, a critical mass of research excellence needs to be developed.

Vaccines both preventative vaccination and therapeutic vaccination against chronicviral infection and non-communicable disease needs further investment to realise theirconsiderable potential. Vaccines could also be used to protect from epidemic zoonoticinfections. Novel vaccine technologies such as DNA vaccines, peptide vaccines andnanoparticle carriers are all exciting new avenues worth exploring. A greaterunderstanding of innate immunity would improve novel adjuvants and mucosal vaccinesand there should also be more imaginative use of vaccines as experimental tools.

Understanding the local immune response is an essential first step in allowing usto alter it. We need to understand the interactions at the point of contact betweenantigens and the immune system as this will ultimately dictate the progression ofdisease. Access to high-quality human tissue samples from established clinics andgreater 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 healthand disease is crucial in developing new treatments for immune-mediated diseases.The field of early life and foetal immune development has been neglected andresearch is needed in this area. Paediatric immunology, particularly the development ofthe immune system in neonates and in infants in relation to infections, vaccines andallergens warrants further study. Research on age-related immune decline will becomemore important as our population becomes an increasingly aged one.

Understanding the life-course of immune diseases will unravel how earlyimmune events dictate disease chronicity. The roles of the chronic inflammatoryresponse; tissue injury and repair; and development of autoimmunity all need to beaddressed to further our understanding of disease chronicity. Longitudinal studies ofdisease and therapy are essential to give us a better understanding of how the diseaseitself changes.

A greater understanding of the determinants of disease process andoutcomes is needed. Understanding the genetic basis for immune disease is still in itsinfancy; identification of novel genes and their functions needs to be improved,embracing a multidisciplinary approach. Greater advantage should be taken of birthcohort studies and other collections for DNA-based studies, epigenetics andconnecting epigenetic mechanisms with environmental epidemiology.


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Addressing disease complexity to understand disease processes and phenotypeswould then identify a range of new targets closer to the origins of the disease andpotential new treatments.

Biomarkers could lead to the earlier identification of disease, give a more informativereadout 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 weneed more sophisticated animal models that better inform the human system, forexample, humanised mouse models and better models of tumour development. Somecreative studies in larger mammals to address chronicity of immune diseases are nowemerging and these should be further encouraged. Although success in thedevelopment of intelligently designed animal models should limit the need for primateresearch, it is likely that ethics committees would still require pre-clinical data fromprimates for some studies and this needs to be delivered.

In vitro models and techniques should be improved and used alongside novel animalmodels. For example 3D in vitro models and in silico techniques could be used tomodel the interaction of immune cells and to study the interaction of cell receptorsand their ligands. There also needs to be greater access to high-quality human tissuefrom 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 functionfrom molecular and intracellular level right up to high resolution whole body imaging.Greater access to existing and improved facilities will benefit the human immunologycommunity.

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 environmentwould have a very large impact on the development of structure-based drug designand on the analysis of structure-activity relationships. There is also tremendouspotential for structural genomics and for post-genomic biomedical research.

Translating our knowledge of human immunology in health and disease isessential to develop new treatments and therapies. Experimental medicinestudies, small-scale studies looking at ‘first-in-human’ experiments, are essential asproof-of-concept for many treatments. Experimental medicine studies will beinstrumental in identifying and establishing novel biomarkers of disease and correlatesof protection of various treatments. These studies may also be of benefit in areaswhere animal models are lacking such as immunity in ageing.

Cohorts should be better used with further establishment of different cohorts tostudy large populations in health and disease. It is essential that they have long-termsupport to provide the necessary infrastructure and management required to extractas much information as possible. Long-term support is essential to allow cohorts tolook longitudinally at many issues, for example, the long-term consequences ofimmune 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 studieslooking at the short, medium and long-term immune responses after vaccine delivery.Primary genetic immunodeficiencies could also be used as models to investigateimmune function.

Genome sequencing and genome-wide association studies are expanding ourunderstanding of the genetic components of diseases. Following the identification ofgenes involved in disease processes, we will also need to identify the gene productsand mechanisms downstream. Huge advances in genome sequencing have allowedrapid sequencing of entire genomes making ‘personalised-medicine’ a realisticprospect. The fields of epigenetics, gene constellations, gene silencing, histoneacetylation and microRNAs in understanding gene/environmental interactions are intheir infancy and require more investment.

Developing a ‘systems medicine approach’ will allow us to integrate all levels ofinformation derived from new technologies and tools. This will require input from arange of disciplines including but not exclusively basic scientists, clinicians, modellersand computational biologists. The models produced should be consistent with theexperimental medicine approaches so that they respond to changes in phenotype andtreatments and so can be further refined.

Improved bioinformatics will be needed to translate the vast amount of novel datagenerated into knowledge. It will be essential to include bioinformatics andinformation 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’ onhow to implement them. We have set out a number of proposals that are keymilestones in creating a clear and distinctive roadmap to realise our scientific visionand strategy.

Creating an interdisciplinary environment will be essential to take humanimmunology research forward. Specialists need to work side by side in an interactivemultidisciplinary environment as opposed to ‘generalists’ in the lab. The mostsuccessful examples of interdisciplinary working are led by individuals with the drive to


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create this environment. The MRC should attract the right people to new posts. Inorder to translate research from lab to the clinic and also the other way, there needs tobe easier iteration at the basic/clinical interface.

Building capacity is a recurring theme throughout this report. Immunology researchneeds strengthening particularly in the disciplines of paediatrics, geriatrics and globalhealth as well as the core disciplines mentioned above. There is also a serious lack ofclinical academics to fulfil the translational research agenda. Also, basic scientistsshould be encouraged to undertake some clinical training. Building and retainingcapacity in basic research is also essential. The MRC should consider using four-yearPhD schemes to increase young scientists’ exposure to a range of labs and, in additionto the response mode schemes, establishing a ‘doctoral training account’ forestablished centres to train new clinical academics.

Sustainability of research activity also needs to be maintained. We recommend thatthe MRC, in partnership with universities, make some key leadership appointments instrategic areas, not only to boost capacity but to stimulate new research in that area.

Increasing connectivity will deliver multi-disciplinarity and build capacity but isdependent on creating sustainable partnerships between institutions and sectors. Weneed to create and increase partnerships between universities, the industrial sector andthe 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. Productdevelopment 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. Thesepresent excellent opportunities for industry and academia to collaborate. Industrycould also make products available to academics for testing in new experimental andclinical models – allowing new avenues to be explored with much smaller risks. Thereshould also be a greater exchange of personnel between academia and industry forexample, through training or joint appointments.

Partnering with the Health Departments to integrate UK health research strategyis 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 intohealth and economic benefits in the UK through better coordination of health researchand more coherent funding arrangements to support translation. The new structuresunder this arrangement offer significant opportunities to develop clinical immunology,engage with industry and ensure increased translational research whilst maintaining


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basic research. The NIHR Biomedical Research Centres will be instrumental in increasingconnectivity between basic and translational research. Also, the NHS is an under-usedresource and we recommend that research be incorporated into the reality of NHS lifeand that the immunology community engages with the Health Departments on howbest to achieve this. The NHS is the point of delivery for vaccines in the UK and so canalso play a role in long-term vaccine research and immunity studies. Cross-disciplinaritywill 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 intothe ‘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 comprehensivespending review settlement will offer new opportunities for human immunology. It isessential to continue response mode funding but there also needs to be some focusand selectivity introduced to achieve strategic impact. To promote new partnershipsand increase connectivity, an immunology network should be established. The size andshape of this network needs consideration but there are already some examples thathuman immunology could follow. Multi-institution/sector consortia are also a strongroute 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 towork with anybody wanting to conduct such research. For those not in the majorcentres, collaboration with these managers could then be encouraged.

Medium-term objectives are to attract and recruit new individuals to neglectedresearch areas; better integrate ‘human’ and ‘mouse’ immunology; and increasecapacity. 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 mechanismsfor this and both have advantages and disadvantages. Whatever the mechanism, forthese to succeed in the human immunology field, they should be closely integratedinto universities with associated medical schools and be highly interdisciplinary.

The long-term vision would be the implementation of this ‘strategy’ as a whole. Thecompletion of the new UK Centre for Medical Research and Innovation (CMRI) is anexciting future opportunity for long-term human immunology research.

www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC00530


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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

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 KimberUniversity of Manchester

10.40 - 11.00 An introduction to challenges for Prof I Kimberresearch into the immunology of University of Manchesterfood allergy.

Session 1 : Current challenges in understanding the immunology of food allergy

11.00 - 11.25 Key challenges in food allergy research Prof G Lackcurrently 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 Nicolettifood allergy. IFR

12.00 - 12.10 Questions

12.10 - 12.35 Understanding the allergenicity Dr Rebecca Dearmanof proteins : a role for immunotoxicology. University of Manchester

12.35 - 12.45 Questions

12.45 - 1.30 Lunch


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Session 2: Emerging topics in immunology

1.30 - 1.55 Title to be confirmed :The role of T-cells Prof Fiona Powrieand their products in immunoregulatory Oxford Universitymechanisms 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 HaydayUnconventional T cells. Kings College London


2.40 - 3.05 An overview of novel imaging techniques Prof Paul Garsidethat could be applied to food University of Strathclydeallergy research.


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 Kimberbetween the two fields of research

4.45 - 4.55 Summary Prof I Kimber

4.55 - 5.00 Closing remarks

Close

© Crown copyright

Published by Food Standards Agency

March 2010

FSA/1560/0310

Documents

Report of a joint FSA-MRC scientific workshop