NIHRDataInsights/HRCSData huggingface dataset:
Title: Novel use of Machine Learning to prevent consumer injuries and product recalls resulting from errors in food supply-chain data
Funder: Innovate UK

Abstract: Food allergies occur when your immune system reacts to a harmless food protein, which are often due to the creation of Immunoglobulin E (IgE) antibodies which are specific for that particular protein. When the protein is consumed, the antibodies recognise the protein and link to it, causing the release of substances such as histamine, which will result in allergic symptoms. An immediate reaction (within two hours of eating the food), usually involves IgE antibodies, and the development of classic symptoms such as an itchy rash, swelling and in some cases vomiting and diarrhoea. Symptoms can vary in severity and can, in the worst case, lead to life threatening problems including difficulty in breathing and collapse, also known as anaphylaxis. LiberEat provides the only digital resource to offer product scanning, product filtering, menu filtering, and a recipe bank all in one place. We allow multiple profiles, which helps users to see exactly who can eat every product, dish and recipe via our app. We ensure our data comes from reliable sources and we never screen scrape, we only work with partner restaurants who give us the information directly. LiberEat was recently named as a winner of the Tech Nation Rising Stars 3.0 Scotland and UK Competitions and selected for Tech Nation's applied AI program. This project will now add the ability to detect discrepancies in declared allergens, identify situations where there is a higher risk of errors, and allow our allergen identification technology to be integrated into supplier allergen management systems. The technology will become a vital safety net to catch the mistakes we know from experience are being made through human error. The proposal has been validated by several food service chains and food producers, a number of which will be involved in testing during the project.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Revive Adrenaline Auto-injector: Industrial Research
Funder: Innovate UK

Abstract: An adrenaline auto-injector (AAI) is prescribed to people who are susceptible to severe allergies that put them at risk of anaphylaxis -- a life threatening allergic reaction. Despite medical advice to carry the injector on person at all times, our user studies show: 1. People do not carry them nearly as much as they should 2. Not receiving adrenaline for an anaphylactic reaction is the biggest common factor in fatalities as adrenaline is the only drug known to prevent death due to anaphylaxis 3. Women are a key area of concern as current needle lengths do not guarantee intramuscular delivery in this patient population Revive is a new AAI concept developed as a graduation project at the _Royal College of Art (RCA)_. After successful technical feasibility of the Revive auto-injector in the Innovate UK Smart Grant January 2020 we can undertake activities for experimental evaluation at laboratory scale, evaluate proof of concept and safety, and explore potential production mechanisms in this proposed project. This project proposal is to validate the preliminary adherence to the regulatory requirements of an AAI and particular attention will be paid towards the supply chain (proof of concept aseptic filling and stoppering for container closure integrity in a lab-scale model). We will also conduct a user study to quantify comparative increase of our device being carried vs. existing products. Designed with the patient at its centre, its credit card size makes it easy to carry and its form makes it discreetly fit within a patient's life. These combine like never before to counteract the identified problems of being too large to practically carry continuously. Revive, unlike most current offerings in the market, incorporates the UK Resuscitation Council's recommended guidelines for a longer needle to reduce the gender disparity in allergy management systems. Revive achieves this through a fresh examination of how a syringe should be designed for an AAI. The proprietary needle injection system concept has been awarded InnovationRCA's support and is patent pending in the UK (Intellectual property office has moved application towards grant). The company is currently incubated at InnovationRCA, Medcity's Pilot Community Program and part of NHS Innovation Service Beta program. It has received publicity from _The Evening Standard_ & _Blueprint magazine_ and also won support from the Global Grad Show, British Invention Show and Embryo Ventures.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Exosomes as tools for cell-to-cell communication during inflammatoty processes
Funder: Welsh Government Office for Science

Abstract: This project aims at decoding the messages exchanged between mesenchymal stem cells (MSC) and macrophages (MF) during inflammation with the ultimate goal of developing bio-inspired exosome-mimetic vesicles for tissue regeneration


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.2 CELLULAR AND GENE THERAPIES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Sêr Cymru II Chair in Systems Medicine
Funder: Welsh Government Office for Science

Abstract: We propose the recruitment of a Sêr Cymru Chair, Professor Peter Ghazal, for Cardiff University’s College of Biomedical & Life Sciences, based in the Systems Immunity University Research Institute (SIURI) and School of Medicine. Prof Ghazal’s relocation to Wales as an active researcher running his own translational research programme as well as contributing to high-level strategic development of systems inflammation research would be transformative in terms of impact, collaboration and innovation in an area of high global importance. The appointment will act as a major enabler for Wales’ efforts to drive research in the area of clinically focussed systems research in infectious and inflammatory conditions, especially diseases of early life. Importantly, it will catalyse Wales’ ability to commercialise/innovate in the emerging area of “Precision Medicine” –relating to next generation diagnostic and therapeutic design innovations using ‘omic’ patient data derived from genomics and metabolomics. While immune-based diseases and the linkage to metabolism are obviously well positioned for advancing precision medicine, to date, no single clinical research or service laboratory embracing a fusion of these approaches has been established. This appointment lays the groundwork for such a Centre to deliver and an opportunity for Wales to be world leading in this area.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: determining the role of the enzyme dipeptidyl peptidase I (DPPI) in allergic inflammation, and investigate factors regulating the expression, activity and secretion of DPPI and other enzymes responsible for activating mast cell proteases. The project should allow evaluation of DPPI as a new therapeutic target in asthma and other inflammatory conditions
Funder: The Academy of Medical Sciences

Abstract: investigate also the HMC-1 (Mayo Clinic) and LAD2 (NIH) human mast cell lines, and the basophil-like line, KU812. For comparison, mast cells will be maintained in short term culture following purification from lung tissue (obtained at surgical resection) by application of an immunomagnetic purification procedure .Expression of mRNA for tryptase, chymase and carboxypeptidase will be monitored by TaqMan quantitative RT-PCRFlow cytometry will be performed on permeabilised cells with antibodies specific for chymase, tryptase, and carboxypeptidase. Enzyme histochemical techniques will be applied. Evidence will be sought for altered expression of mast cell proteases, and findings will be compared with those of mast cells in comparable tissues from subjects without this condition, and in cultured mast cells.Cellular expression of DPPI: Monoclonal antibodies specific for DPPI prepared by the host laboratory will be applied to determine the distribution of DPPI in cultured mast cells and cell lines, and in other cell types by immunocytochemistry


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: In Utero Therapy for the Induction of Immune Tolerance
Funder: The Academy of Medical Sciences

Abstract: In this study, I aim to show therapeutic engraftment (which is engraftment of more than 20% of the total CD45+ cells in the bone marrow (BM) of the recipient mice) in a mouse model of in utero transplantation using BM partially matched, allogenic, haematopoietic stem cells (HSCs) with Tregs. Initially, I will harvest and expand Tregs from the spleen of the donor mouse (FoxP3 eGFP, B6.Cg-Foxp3tm1Mal/J). The FoxP3 model will be used in order to be able to trace the Tregs in vivo since they express GFP. The BM HSCs will be isolated from adult mouse BM F1 (BALBc/j x FoxP3 eGFP, B6.Cg-Foxp3tm1Mal/J) using lineage depletion and CD117/Sca1 positive selection. The in utero transplantation will be performed as described at E13.5 and I will study the fate and function of transferred Tregs in the wild type CD57BL6 mouse as well as their ability to enhance the HSCs transplantation potential. I will compare BM HSCs and BM HSCs-Tregs transplantation. I will use a stereo microscope to trace the Tregs, as well as flow cytometry to trace BM HSC Donor cells using donor-specific antibodies (H2Kd). The serum from the injected Dams and recipients pups will also be kept in order to perform antibody response assays. Multilineage analysis will be done at embryonic day 18 initially and then postnatally as described in the main text to assess if there is a gradual rejection of the transplanted cells and stable engraftment. The engraftment will be assessed for a maximum of 8 weeks.

Lay abstract: Diseases which are inherited through families, such as those affecting the genes in red blood cells eg sickle cell disease, are not very common but can have a serious effect on health. this project will study whether replacement of the faulty red blood cell in the developing baby whilst still in the womb could correct or reduce the problem before the baby is born. In this project, we will aim to "reprogram" the early fetus by using new technology which will allow the recognition of the donor cells with the corrected genes as ‘self’. This project will address the need to maximise the efficacy of stem cell (HSC) transplantation and to promote the correction of gene disorders in utero. The project is novel especially because it will complement and enhance the current transplantation research programme at KCL in defining the contribution of immune cells, namely Tregs, in facilitating HSC-mediated survival of fetuses. . In addition, the use of a clinically relevant sickle cell disease model meets the translational challenge of promoting correction of single gene defects prenatally

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Investigating the role of WNK1 in T cell killing
Funder: The Academy of Medical Sciences

Abstract: Cytotoxic CD8 T Lymphocytes (CTL) are a critical component of the adaptive immune system and are responsible for clearing virus infected cells and cancer cells by secreting a deadly cocktail of cytolytic enzymes through a specialized structure called the cytolytic synapse. This project aims to study the biochemical pathways that underly T cell killing. Particularly, we are interested in the serine/threonine kinase WNK1, which until recently was mostly known for its role in regulating ion homeostasis in the kidney, but from which we now know is also a novel positive regulator of T cell killing. Previous data by our lab has shown that in CTLs WNK1 is a negative regulator of integrin-dependent adhesion and a positive regulator of migration in response to chemokines. New data obtained from CTLs doubly deficient for the well-studied WNK1 effectors OXSR1 and STK39, shows, that these, despite having the same adhesion and migration defects kill normally, suggesting that the killing defect is not due to those WNK1 function. We therefore hypothesize that WNK1 directly controls the formation of the immune synapse by phosphorylating novel yet to be determined substrates. We will therefore use a two-pronged approach and use high resolution imaging modalities to determine which step in the killing cascade is defective in combination with phospho-proteomics and biochemistry experiments to elucidate the underlying signalling pathways.

Lay abstract: Cytotoxic T cells are a critical part of our immune system. They are the white blood cells responsible for detecting and destroying virally infected cells and cancer cells. For them to function properly they first need to migrate to the site of infection or into the cancer tissue. They then tightly adhere to their targets before killing them. Our research focuses on cytotoxic T cells and we plan to determine how the above-mentioned killing process is carried out. Particularly, we will investigate the function of a protein called WNK1, which previously has only been studied for its role in salt reabsorption in the kidney, but which we now know plays vital roles in T cell biology. We know that WNK1 controls both the adhesion of cytotoxic T cells to infected cells or cancer cells as well as their subsequent removal (“killing”). We will therefore investigate how WNK1 participates in transmitting the biochemical signals from the surface of the T cell to its adhesion and killing machinery. The knowledge gained in this study will help to develop drugs that can either inhibit or enhance the function of T cells and will therefore impact on developing treatments against viral infections, autoimmune diseases or cancer.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Zooming in on adaptive immunity with high-speed super-resolution microscopy
Funder: The Academy of Medical Sciences

Abstract: The aim of this project is to enhance the speed of super-resolution microscopy to improve our understanding of how the T-cell receptor (TCR) is triggered. My objectives are to develop a novel high-speed super-resolution microscopy technique, to apply it to visualise reorganisation of membrane proteins during T-cell activation and compare it to the mechanism of an immunotherapy drug ImmTAC. The findings will be used to identify new molecular targets and mechanisms for adoption in immunotherapy, with the aim of improving efficacy and specificity. T-cells are capable of targeting pathogens without destroying healthy tissue, however our understanding of how membrane proteins organise to achieve this is limited as conventional fluorescence microscopy cannot visualise the dynamic nanoscale processes involved. T-cell redirection is a recent anti-cancer strategy that utilises this activation mechanism and has been particularly successful for targeting blood cancers. By improving optical techniques to visualise the T-cell activation process it will be possible to identify which proteins are key for maintaining specificity and the mechanisms involved, which offers new routes to designing T-cell redirection therapies. I will develop high-speed super-resolution imaging, to enable real-time observation of nanostructures in living cells. I will apply this technology to observe how membrane proteins organise during T-cell activation and compare this to cells activated by the immunotherapy drug ImmTAC. The success of this proposal will lay the foundation for the development of 3D super-resolution microscopy in living cells, which will for the first time enable nanoscale visualisation of T-cell activation in cell-cell contacts.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Pre-clinical studies for a stem cell gene editing platform to treat primary immunodeficiencies
Funder: LifeArc

Abstract: Children born with severe Wiskott-Aldrich syndrome (WAS) experience wide-ranging symptoms and are at risk of early death without proper treatment. Symptoms of this immunodeficiency disease include easy bruising, bloody diarrhoea and prolonged bleeding following nose bleeds or minor trauma. They are more vulnerable to infection and at higher risk of developing certain cancers. WAS is caused by errors written into a section of DNA, the X-chromosome. WAS affects almost exclusively boys – around three in every million worldwide – because females have two copies of the X-chromosome and males just one. This gives females an insurance against the errors in one X-chromosome that cause WAS. As there is no effective treatment, many people born with WAS die before they are 20. The current standard treatment is a bone marrow transplant, but only around 20% of patients can find a suitable matching donor. Last year Dr Alessia Cavazza’s team published encouraging results for an adapted gene therapy. Using CRISPR-Cas9 technology – sometimes called ‘molecular scissors’ – they made a physical cut through DNA at the precise place where the WAS gene is usually found. This guided the gene delivery system to slot the corrected gene into the part of the sequence where it is found in a healthy person. This precise placement of the WAS gene corrected around 60% of cells, while leaving them otherwise unaffected. These cells continued their normal life cycle of maturing into different types of immune system cells. The team aims in this project to confirm the safety of this particular gene editing technique. If they do, they could start clinical trials at Great Ormond Street Hospital in 2-3 years. The hospital sees around 20-25 patients with WAS each year.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.2 CELLULAR AND GENE THERAPIES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Randomised controlled trial of early introduction of allergenic foods to induce tolerance in infants (EAT trial)
Funder: Medical Research Council

Abstract: In the UK 6% of children under the age of 6 years will develop food Allergies (FA), 25% eczema, 20% asthma and 10% allergic rhinitis (AR). DH guidelines advise exclusive breast feeding (EBF) for the first 6 months and delayed introduction of allergenic foods. There is little evidence that this reduces allergic disease. Interventional trials of delayed weaning have consistently failed to reduce FA and atopy. Animal models and preliminary human data demonstrate that high dose oral tolerance to food proteins in early life prevents allergic sensitisation. Three separate studies show that prolonged EBF is a risk factor for developing atopic disease. The trebling of allergic disease since the 1970s has coincided with a two-thirds reduction in early weaning. Thus delayed weaning could promote FA and even other atopic diseases. We propose a randomized controlled study in infants to determine whether early weaning and exposure to food allergens (3 months of age) prevents the development of FA, eczema, asthma and AR. This study will provide an informed basis for future weaning practices in both atopic and normal infants.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;3.3 NUTRITION AND CHEMOPREVENTION
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: Characterisation of the cellular mechanism that prevents the development of insulin-dependent diabetes mellitus 2
Funder: Medical Research Council

Abstract: The size and composition of the peripheral T cell compartment is remarkably stable in spite of constant production of new T cells from the thymus and during immune responses. This homeostasis is achieved through the highly specific regulation of survival, proliferation and death of T cells within the peripheral T cell compartment. What is more, the specific mechanisms that regulate homeostasis vary depending on T cell lineage (CD4 vs CD8) and states of differentiation (Naove vs memory). Cytokines and signals via the T cell antigen receptor (TCR) are among the chief environmental queues involved. In the latter case, TCR signals elicited by the recognition of self peptide-MHC complexes result in survival or cell division but not differentiation of T cells.The focus of the research within my group is to better understand how these signals contribute to the regulation of peripheral T cell homeostasis. To achieve this, we are developing novel mouse models that will permit genetic manipulation of the signalling pathways involved. To this end, we have developed mice that conditionally expression IL-7 receptor and Zap70, a key kinase in the transduction of TCR signals. With these models, we will be able to precisely quantify the contribution of these receptor signals to the homeostasis of the various subsets of peripheral T cells. They will also allow us to dissect the roles of the different signalling pathways downstream of these receptors and identify the genes whose expression is crucial for mediating homeostatic responses by T cells.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: INFLAMMATORY AND IMMUNE SYSTEM
Title: The signaling pathways that regulate the production of pro-inflammatory cytokines
Funder: Medical Research Council

Abstract: Aims 1. To dissect the protein kinase cascades activated proinflammatory cytokines, infection and cellular stresses. 2. Elucidation of the physiological roles of each protein kinase that participates in this process. Plan of Investigation The techniques of protein chemistry, enzymology, cell biology, molecular biology, immunology and mouse genetics are being used to elucidate the molecular mechanisms by which infection by bacteria and viruses stimulate the production of pro-inflammatory cytokines, interferons and chemokines and why the deregulation of these pathways causes immunodeficiency diseases, increased susceptibility to bacterial infection, inflammatory diseases like Rheumatoid Arthritis and Crohns disease and autoimmune diseases such as Lupus. Our recent research has helped to elucidate the intracellular pathways that control the production of pro-inflammatory cytokines and interferons and pinpointed protein kinases that are attractive targets for the development of drugs to treat these diseases. Scientific/Medical and Commercial Opportunities Drugs that inhibit the protein kinases in these pathways may be efficacious for the treatment of chronic inflammatory diseases. Indeed such efficacy has already been demonstrated in some cases. These drugs are, however, likely to have additional/alternative uses; for example to treat cancer, or prevent tissue rejection during organ transplants. We facilitate the development of protein kinases inhibitors to treat disease through a collaboration between our MRC Unit and six of the worlds major Pharmaceutical companies that started in 1998. We have also been collaborating with MRC Technology to help them develop a new drug that suppresses interferon production. In addition, many of the reagents that we have developed are marketed by Millipore. This provides the Unit with significant revenue to support its research, and another benefit of this relationship was the setting up of a new company (Upstate Discovery Ltd) in Dundee, that now employs 70 people.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM