NIHRDataInsights/HRCSData huggingface dataset:
Title: Role of neuro-immune-epithelial interactions in the initiation of Parkinson's Disease within the gut
Funder: Wellcome Trust

Abstract: Parkinson’s Disease (PD) is generally known as a neurodegenerative disease that affects motor function; but it is also frequently associated with abnormalities in the gut. Indeed, many scientists believe that PD might start in the gut. This is because a key biological sign of PD, a mis-folded protein called &alpha;-synuclein (&alpha;-Syn), can first be found in the nerves and brain regions that connect to our intestines. However, evidence for this theory comes largely from animal studies. In humans, we only have “correlational evidence”. For example, if you have inflammatory bowel disease, you are more likely to develop PD. With my PhD, I aim to develop a human cell culture model to help study whether PD starts in the gut. I will grow human intestinal organoids with different types of gut neurons made from human pluripotent stem cells. I will then investigate how inflammation of this system affects the communication between different cell types and whether it will make it more likely for misfolded &alpha;-Syn to “cross-over” from the gut organoids into nerves. My system will help better understand what initially causes PD, with the hope of identifying new ways to prevent or treat it early, before it reaches the brain.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL;NEUROLOGICAL
Title: Detailed exploration of the market need for a novel solution for the hypothermic machine perfusion of abdominal organs
Funder: Department of Health and Social Care

Abstract: LS-A (Leeds-Solution-Abdominal), is a novel static cold storage (SCS) solution for preservation of abdominal organs between removal from donor and transplantation. SCS is standard clinical practice; the organ is placed in hypothermic preservation solution to minimise metabolic activity and ischemic damage during transport. LS-A improves preservation, outperforming &ldquo;gold standard&rdquo; SCS in animal models and will progress into clinical investigation late2022/early2023, pending further funding[1]. This project explores if the clinical use of LS-A should be expanded to machine perfusion as well as simple cold storage. The number of donor organs is dwarfed by clinical need; patients wait years for transplant and 7500 people die on waiting lists each year in Europe and US[2]. The need for transplant is growing with aging population and prevalence of complex co-morbidities. The global organ preservation market is projected to reach USD 317 million by 2026 at a CAGR of 6.6%[3]. Innovations in SCS are scarce but machine perfusion (MP) systems have been developed to increase the pool of donated organs, growth in this market sub-section dominates. MP systems actively pump solutions through the organs; benefits include improved preservation and the ability to make real-time assessments of organ function[4]. Accurate assessment, even treatment, whilst outside the human body could significantly increase the number of successful transplants in a cost-effective manner[5]. This project explores if and how OPSL should develop LS-A to meet the needs of the MP market in order to expand the business case for onward investment. We will explore the need for a novel MP solution, key product requirements and necessary technical modifications to existing LS-A. The project involves a combination of desk-based research and interviews with surgeons, perfusionists and other stakeholders. The funding is needed now to refine commercial strategy to reflect current market trends and to strengthen OPSL's campaign for further investment.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: ORAL AND GASTROINTESTINAL;RENAL AND UROGENITAL
Title: Environmentally sustainable and reusable incontinence products for men, women and children
Funder: Innovate UK

Abstract: With a core team of Richard Summerfield, Frances Lucraft, Vera Chetty and Nikki Cotterill, Eco Hygiene Care Ltd (ECH) is a UK Health and Hygiene SME which has recently established a successful existing product in the period care market (Grace & Green). Building on this expertise, EHC is partnering with research institutions to develop a range of incontinence products to meet the growing market demand across all age groups, along with the desire for solutions that are reusable, sustainable and affordable. The company also invests in corporate responsibility and charitable giving.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: ORAL AND GASTROINTESTINAL;RENAL AND UROGENITAL
Title: Investigation of the effect of male cholestasis on the epigenome of sperm and the impact on the health of children of men with cholestasis.
Funder: PSC Support

Abstract: Aims to address unanswered questions around ‘Aetiology and identification of subpopulations of PSC’ and ‘Treatment’. It will establish whether men with PSC have altered sperm, and aims to establish whether the observed alterations are reduced or prevented in those treated with ursodeoxycholic acid. Similarly, it will investigate whether cholestasis when fathering a child results in the children having an increased risk of having metabolic disease in later life (and whether this is less likely if the father was treated with ursodeoxycholic acid).

Lay abstract: as per abstract

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Utilisation of N-glycans from breast milk by infant-associated microbes
Funder: Wellcome Trust

Abstract: The human gut microbiota is a dense and interdependent community and has a mutualistic relationship with the human host. These microorganisms have significant but poorly-understood impacts on health, development, and disease. The major carbon source for these microbes are glycans and polysaccharides and a proportion of these are derived from the host, such as those from mucins and immunoglobulins. This research will focus on how the infant gut microbiota uses the N-glycans in breastmilk as a nutrient source. These N-glycans are an abundant nutrient source for the infant gut microbiota, but remarkably understudied in this context. The anticipated output of this research would be to highlight healthcare improvements, such as pre- and probiotics, that can be made for those infants that do not have access to breastmilk. This is significant as the UK has one of the lowest rate of breastfeeding in Europe, with only 34 % of mothers continuing to 6 months and 0.5 % to 12 months. This output will be achieved by producing a detailed molecular understanding of the enzymes used by Bifidobacterium spp. to access this nutrient source. This study will also characterise how these nutrients are cross-fed between different species and strains.

Lay abstract: There are more bacteria in a person’s gut than there are stars in our galaxy and it is the densest ecosystem on the planet. These microorganisms are collectively known as the human gut microbiota and we have a mutualistic relationship with them; we provide them with nutrients and they contribute to health throughout our lives. This is especially important for our development when we are very young. To understand the many connections that form this complex relationship in infants, my research focusses on how these microorganisms extract their nutrients from breastmilk glycoproteins. I will look how the bacteria use these nutrients and characterise the molecular details of the key enzymes. The findings of this project will provide new prebiotics and/or probiotics for use in infant formula to increase its similarity to breastmilk. This will provide those infants without access to breastmilk with the health advantages that are associated with breastmilk.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: ORAL AND GASTROINTESTINAL;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: RegenVOX: phase I/II clinical trial of stem cell based tissue engineered laryngeal implants
Funder: Medical Research Council

Abstract: There are no satisfactory conventional solutions for patients with end-stage laryngeal stenosis, which can result from trauma or after cancer resection. This has profound impacts on quality of life, especially swallowing, breathing and talking. Based on our 'first-in-human' successes with tracheal implants1,2, we developed an autologous stem cell and biologic scaffold based partial laryngeal implant to correct severe structural disorders. In preclinical studies, this was biocompatible in rats, and safe and effective in pigs (human cells in immunosuppressed animals). We have developed robust processes for production of cells, scaffold, bioreactor and implant within our fully Good Manufacturing Practice (GMP) licensed cell therapy facility. UCLH hosts the national airway service, which has the largest pool of potential recipients in Europe, and skilled clinical staff. We propose a 50 months' project to encompass a phase I/IIa clinical trial of customized stem cell based laryngeal implants in ten patients with severe laryngeal stenosis who have exhausted conventional therapeutic options, and with two years' follow-up. Milestones will be: 1. Obtain necessary authorisations, and perform first implant 2. Complete recruitment and submit processes for IP assessment 3. First two patients attain 6- and 12-month efficacy targets; cost-reduction achieved 4. Completion of follow-up, reporting to MRC and MHRA and publication in high impact journal


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: ORAL AND GASTROINTESTINAL;RESPIRATORY
Title: Clinician Scientist: Prevention by HMGCoA reductase inhibition of ARDS associated with one lung ventilation following oesophagectomy by a Reduction of Pulmonary vascular dysfunction and inflammation (Prevention-HARP 2)
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Complications of the lung (in severe cases lead to a condition called Acute Respiratory Distress Syndrome (ARDS)) and heart (heart attack) are serious and can occur after surgery such as removal of the food pipe (oesophagectomy). In this research, we will investigate the potential of simvastatin (a cholesterol lowering drug) in reducing the occurrence of these complications. This research conducted in multiple UK hospitals, will follow methods that will ensure high quality research. The researchers and patients will not be aware of whether they are on the study drug (simvastation) or a dummy pill (placebo) and this allocation will be made by a computer system. This will ensure that the results are not influenced by the study team. The development of these complications can lead to the need for artificial breathing support, stay in intensive care unit, longer hospital stay, a prolonged period of recovery amongst survivors or even death. This will also result in immediate and long-term costs to the NHS. Simvastatin could significantly improve outcomes in patients if shown to reduce the incidence of lung and heart complications after surgery and will also prevent additional financial and resource burden to the NHS.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: ORAL AND GASTROINTESTINAL;RESPIRATORY
Title: Development of in-vivo 19F Clinical MR imaging Using a Novel 19F/1H Coil in Combination with an Intravenous Perfluorocarbon (ABL-101)
Funder: Wellcome Trust

Abstract: Inflammation is part of the body's defence system against a wide range of harmful stimuli.Inflammation also plays an important role in human diseases, including stroke, Alzheimer's,hardening of arteries, arthritis, and cancer. The ability to image inflammation inside thehuman body would provide an improved understanding of this process and provide newopportunities for diagnosing disease and guiding treatment. ABL-101 is a fluorinated oxygencarrier which is being investigated for treatment of stroke. It is made up of a large number offluorine atoms that can be visualised in MRI using a detector that is tuned to fluorine (19FMRI). Once injected, cells that are also part of the inflammatory response (macrophages)take up ABL-101. ABL-101 could therefore be an imaging agent for inflammation. 19F MRIuses a specially developed radiofrequency coil and some specialised programming that DrSantosh and the team at the University of Glasgow wish to assess as a vital step todeveloping clinical uses.

Lay abstract: Inflammation is part of the body’s defence system against a wide range of harmful stimuli. Inflammation also plays an important role in human diseases, including stroke, Alzheimer's, hardening of arteries, arthritis, and cancer. The ability to image inflammation inside the human body would provide an improved understanding of this process and provide new opportunities for diagnosing disease and guiding treatment.ABL-101 is a fluorinated oxygen carrier which is being investigated for treatment of stroke. It is made up of a large number of fluorine atoms that can be visualised in MRI using a detector that is tuned to fluorine (19F MRI). Once injected, cells that are also part of the inflammatory response (macrophages) take up ABL-101. ABL-101 could therefore be an imaging agent for inflammation. 19F MRI uses a specially developed radiofrequency coil and some specialised programming that we wish to assess as a vital step to developing clinical uses.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL;STROKE
Title: Using ABM to examine how social network formation processes shape drinking behaviour and alcohol-related harm
Funder: Wellcome Trust

Abstract: Drinking behaviour of one’s friends is found to be a strong predictor of one’s alcohol use, especially among adolescents. Two mechanisms have been extensively explored to explain drinking similarity among friendship groups: 1) selection, i.e. adolescents choosing to become friends with those who have similar drinking behaviours, and 2) influence, i.e. adolescents changing their drinking behaviours to match with their friends. The main aim of this study is to develop or adapt an agent-based model (ABM) to examine how social network formation processes shape drinking behaviour and alcohol-related harm. We will focus on exploring the bidirectional relationship between drinking behaviours and friendship groups among first year university students, and its health economic consequences. This study will build on the social contagion theory ABM developed by the CASCADE (Calibrated Agent Simulations for Combined Analysis of Drinking Etiologies) project, which will be calibrated by evidence found in literatures and collected from first-year undergraduate students at the University of Sheffield via web-based questionnaires. We aim to provide insights on the how social network formation processes shape drinking behaviour and alcohol-related harm among young British adult drinkers, when they drink within a newly formed friendship group, and inform individual-level or group-level intervention policies accordingly.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: ORAL AND GASTROINTESTINAL;STROKE;CANCER AND NEOPLASMS
Title: Targeting the gut in metabolic disease
Funder: Wellcome Trust

Abstract: This project aims to identify new strategies to target the gut for the treatment of type 2 diabetes and obesity. Intestinal hormones regulate intestinal nutrient absorption, insulin secretion and appetite, and therapeutics based on the gut peptide GLP-1 are widely used for type 2 diabetes and obesity. Bariatric surgery causes weight loss and resolves diabetes at least in part via gut endocrine changes. This project will characterise human enteroendocrine cells using intestinal organoid cultures, building on our previous work using transgenic mouse models. To identify cells of interest, organoids will be engineered by CRISPR/Cas9 to express fluorescent sensors driven by hormonal promoters, allowing cellular analysis by transcriptomics, electrophysiology and real-time fluorescence imaging of e.g. Ca2+ and cAMP. We will characterize nutrient sensing pathways and identify receptors and signaling pathways potentially modifiable therapeutically. Using mouse and human tissues, we will identify circuitry involved in bidirectional cross-talk between gut endocrine cells and enteric/autonomic nerves. Building on our new methods to analyse peptides and the low molecular weight proteome by mass-spectrometry, we will investigate how plasma peptides respond to nutrient ingestion in health and metabolic diseases including diabetes, obesity, lipodystrophy and anorexia nervosa, and following bariatric surgery or dietary calorie restriction in obesity.

Lay abstract: Hormones from the gut control blood glucose and appetite. Gastric bypass surgery, used to treat obesity, often reverse diabetes, at least partly by increasing gut hormone levels. Peptides based on the gut hormone GLP-1 are already used for diabetes and obesity treatment, and other gut peptides are in clinical trials. To develop alternatives to injecting peptide-based drugs we aim to understand what controls the release of gut hormones. Gut hormone-releasing cells are, however, difficult to identify, so we will tag them with fluorescent markers in human mini-gut cultures. This makes it possible to study these cells in detail and to identify novel ways to stimulate them. We will also look for new gut hormones that are altered after food intake, or in metabolic disease. The long-term aim is to identify new oral treatments for diabetes and obesity mimicking intestinal changes after gastric bypass surgery.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL;STROKE;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE
Title: Assessment of plant-based food suitable for comparative nutritional assessments of dietary anthocyanins for healthy ageing
Funder: Wellcome Trust

Abstract: Healthy ageing poses a constant challenge we are facing globally. We strive for feasible and affordable solutions to combat age-related chronic diseases. Evidence is accumulating of the health-promoting properties of plant-rich diets. Characteristically, anthocyanins are red, purple or blue, and water-soluble pigments, commonly found in many fruits and vegetables. Anthocyanins have drawn considerable interest due to their biological importance and versatile applications in many fields. Notably, dietary anthocyanin intake has been associated with a low risk of human chronic disorders (e.g., cardiovascular disease, type 2 diabetes mellitus and neurological diseases), and consumption mediates inflammatory markers, weight control, memory and is associated positively with mood enhancement.I aim to investigate how the consumption of coloured potatoes containing anthocyanins might contribute to gut and brain health. Overall, the primary objective is to identify varieties of common foods that differ in their anthocyanin content, and the approach is to undertake compositional analysis prior to comparing their efficacy in protecting against chronic disease and/or in enhancing mood and memory. Finally, this study will enable me to gain insights into the mechanisms by which how anthocyanin-enriched foods benefit health, and provide evidence-based recommendations for diets to relieve the socioeconomic burdens of unhealthy ageing.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: ORAL AND GASTROINTESTINAL;STROKE;METABOLIC AND ENDOCRINE;CARDIOVASCULAR
Title: Can renal functional measurements based on Magnetic Resonance Imaging (MRI) detect renal damage following kidney transplantation in children?
Funder: Kids Kidney Research

Abstract: Kidney transplantation is the best form of kidney replacement therapy for children with end stage kidney failure. Despite improvements in surgery for kidney transplantation, and medications used to prevent kidney transplant recipients rejecting the new kidney, damage is seen in over 95% of cases one year after transplant. Current blood tests are insensitive to early kidney damage, so pre-planned kidney biopsy following transplantation (protocol biopsy) is recommended to detect damage, despite recognised complications (bleeding) and limitations of biopsy Biopsy only samples a small part of the kidney; Magnetic Resonance Imaging (MRI) evaluates the entire kidney. New techniques in MRI quantify how different parts of the kidney use oxygen (BOLD) and how water molecules within the kidney are affected by the body’s attempt to reject the transplanted kidney (Diffusion Tensor Imaging (DTI)). The MRI is non invasive as these parameters do not require the injection of any contrast agent. We believe that non-invasive functional MRI may provide sensitive markers of early damage of the transplanted kidney. The principal objective is to establish the relationship between the new functional MRI measurements (BOLD & DTI) and biopsy findings of transplanted kidneys. If successful this may establish MRI as a non-invasive test of renal damage. Sequential changes on MRI within transplanted kidneys will be analysed to see if, in each patient, the trend of these changes offers the possibility of understanding the sub-clinical disease pathway and how treatment may alter this trajectory This project will study children undergoing renal transplantation at Great Ormond Street Hospital NHS Trust. Timed renal biopsy at 2 and 12 months will be undertaken post-transplantation; we propose MRI between 10-20 days and 2, 6, 9 and 12 months post-transplantation. The parent donor will undergo MRI prior to and following kidney removal, thus functional MRI from both the transplanted kidney and the parent’s remaining kidney will be recorded before and following transplantation If successful non-invasive MRI will be a new biomarker of renal function and may alter patient management by allowing timed renal biopsies.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL
Title: Genetics of renal disease
Funder: Kids Kidney Research

Abstract: The majority of kidney disorders in childhood are present from birth (congenital). An inherited (genetic) basis is very likely in these cases. Identifying the underlying gene(s) is desirable, as it provides an accurate diagnosis, which will provide the patient and their family with precise information about the condition, enable planning for care (medical, social, educational) and put them in contact with relevant patient and support organisations. It allows appropriate genetic counselling of the family and informs about treatment and prognosis. Moreover, it provides new knowledge about the nature of the underlying problem and thus enables the development of potential new treatments. Disease gene identification, however, has been difficult due to the labour and time demanding task of sequencing potential underlying genes in order to identify the actual disease-causing mutation. New technologies now dramatically accelerate this process. We propose to apply these new technologies to identify new disease genes and mutations in patients followed at the Renal Unit at Great Ormond Street Hospital.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL