NIHRDataInsights/HRCSData huggingface dataset:
Title: Investigating Fluctuations in the Transcriptional Status of a Gene in Individual Nuclei.
Funder: Wellcome Trust

Abstract: I have developed a way of being able to see a gene in action ie exactly when it is switched on and off in a living mammalian cell, under the microscope. In theory I could use my system to monitor any gene in any cell but the field I am going into is stem cells. Embryonic stem cells have the potential to produce any tissue in the body and therefore are an exciting prospect for future medicine. Adult stem cells are cells which are responsible for the repair of damaged tissues in the body throughou t a human s lifespan. E.g. When lung tissue is damaged or worn out, adult lung stem cells divide to form fully functional lung cells to replace the damaged tissue. Working at the University of Cambridge, I will use my system in mice to look closely at a gene which is important in the functioning of adult lung and embryonic stem cells and to see how the on and off activity of this gene varies depending on what the cells are doing. In the future this could help us improve the way we grow tiss ue from stem cells so that these tissues can be used in medicine.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE;RESPIRATORY
Title: Hair follicle induction by cultured human hair follicle dermal stem cells
Funder: Medical Research Council

Abstract: To a considerable extent, our laboratory has pioneered the concept of hair follicle neogenesis using hair follicle dermal cells as the inductive source. This project provides a key enabling technological step that advances the concept of hair follicle induction towards translational use in humans. The hair follicle dermal papilla is a unique component of the hair follicle, which has been shown to be fundamental for hair follicle cycling, and when isolated from the hair follicle is capable of inducing de novo hair follicle formation (neogenesis). Nevertheless, when human dermal papilla cells are propagated in culture, the hair inductive capability of these cells is lost. By carrying out molecular profiling of dermal papilla cells after they are isolated from the hair follicle and at stages during their subsequent culture, we have established a molecular signature of these cells in relation to their inductive status. We have also demonstrated that manipulating the cultured cells to create three-dimensional structures partially restores their original molecular profile. Our hypothesis is that restoration of genes that are essential for hair follicle induction through a combination of methods will fully restore the ability of dermal papilla cells to induce de novo hair follicles. 1) From our profiling we will introduce key missing transcription factors by transduction ? we will also introduce dermal papilla signature reporter genes into the cells 2) We will manipulate culture conditions by adding secreted factors elucidated from epithelial cells; 3) By spatially restricting three dimensional dermal cell cultures either in a bioengineered matrix or by surrounding them with epidermal cells we will alter the interaction between cells in such a way that we promote a functional in vivo dermal papilla profile. The inductive status of the cells will be tested throughout, using different in vivo functional studies, the most stringent of which assesses follicle neogenesis directly in human skin pre-grafted to immunocompromised mice. The use of these functional assays will be governed in part by reporter readouts. A successful outcome at the end of this project will firmly establish the proof-of-principle for procedures required to achieve hair follicle induction in the clinical setting, thereby providing the opportunity for rapid translational development. Moreover, while bioengineering of hair follicles is an innovative alternative in the hair follicle transplantation field, it is also a key step towards the ultimate aim of creating an engineered skin incorporating skin appendages for skin grafting and replacement.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE;SKIN
Title: Improving diagnosis and treatment for the quantified patient
Funder: Medical Research Council

Abstract: Stratified approaches to the clinical management of disease promise a substantial public health benefit. The proposed research seeks to identify and validate generalisable stratified approaches, using psoriasis as a model disease, based on unique clinical, genomic and population-scale datasets. Firstly, using data generated by the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) project, a genome-wide association study will be completed to identify genetic variants robustly associated with response to multiple biologic therapies. A framework will be established to evaluate combined genetic and clinical predictors of response. A treatment algorithm will be recommended and opportunities to validate it locally or via collaboration will be sought. Secondly, the contribution of genetic and environmental/lifestyle factors to disease course and severity will be investigated. Initial efforts will focus on utilising several established methods to infer and validate psoriasis phenotypes in population-scale datasets such as UK Biobank, including linked electronic health records. Derived data along with PSORT data will be used to refine our understanding of genome-wide psoriasis susceptibility signals via case-control meta-analysis. Genetic and environmental contributions to psoriasis incidence and severity at the population level will be investigated, to include study of gene-environment interaction and comorbidity risk. Thirdly, artificial intelligence (AI)-based skin disease assessment and management recommendations will be developed. Novel data collection mechanisms will be explored to generate sufficiently large/dense longitudinal datasets; for example, image or text data collected via mobile technology. AI frameworks will be developed and evaluated which use these data to predict when clinical intervention can most effectively reduce disease burden. Pilot analyses will focus on analysis of longitudinal image and patient-reported "life quality" data.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE;SKIN
Title: An investigation of circadian rhythms in psoriasis skin and time-of-day dependent response to ultraviolet B radiation
Funder: Medical Research Council

Abstract: I aim to undertake three experiments with a translational focus to investigate the circadian clock and circadian rhythms found in psoriasis skin and compare the response to UVB irradiation applied locally to psoriasis plaques in a powered clinical study. Experiment 1: Mechanistic enquiry (10 patients) Hypothesising that circadian rhythms are present in skin derived from psoriasis plaques, I will carry out lentiviral transduction of epidermal keratinocytes and dermal fibroblasts with a clock gene reporter and quantify the expression of this in real-time over 1 week via luminometry. Experiment 2: Clinical study (16 patients) I have generated pilot data suggesting that clock gene expression varies between the morning and afternoon, and that UVB irradiation to plaques of psoriasis will lead to significantly more DNA damage and keratinocyte apoptosis in the morning compared with the afternoon. To confirm these findings, I will carry out a larger clinical study of 16 patients (powered from pilot data). I will administer a standardised dose of UVB to individual plaques of psoriasis in the AM and PM, then take 6mm skin biopsies from these areas as well as similar non-irradiated areas (four biopsies per patient). I will also take AM/PM blood samples for future RNA and DNA analysis. I will process these biopsies to perform RNAseq and by immunohistochemistry to quantify AM/PM DNA damage and apoptosis. Experiment 3: Bioinformatics enquiry I will use the RNAseq data from my clinical study and also from an existing large cohort study (PSORT, >120 patients with timestamped biopsies) for AM/PM differential expressed gene (DEG) analysis and Ingenuity Pathway Analysis (IPA). This Fellowship will greatly increase the current knowledge about circadian rhythms in psoriasis and provides built-in translational application to phototherapy, a commonly used treatment for psoriasis. Future aims would be a RCT comparing phototherapy outcomes for psoriasis patients.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE;SKIN
Title: Robotic Actuated Imaging Skins
Funder: Royal Academy of Engineering

Abstract: This work will develop robotic surface structures with embedded sensors that can adapt their shape and size using artificial intelligence algorithms to control and interpret sensory information. Using this data, Professor Stoyanov’s new systems will help to enhance imaging capabilities during minimally invasive surgery and enable safer and more precise procedures to treat diseases across different anatomical regions.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE;SKIN
Title: China kadoorie biobank - University of Oxford
Funder: Medical Research Council

Abstract: China has undergone a rapid transition in disease patterns, with chronic non-communicable diseases such as stroke, ischaemic heart disease (IHD), cancer and emphysema (COPD) accounting for most of the remaining mortality and disability. For these diseases, there are still large unexplained variations in the age specific rates between different countries and between different regions in China, indicating that important causes remain to be discovered. Heterogeneity in disease rates, non-genetic risk factors and genetic architecture, between Chinese and Western populations, and between different parts of China, helps identify new risk factors and explore known causes more comprehensively. This is particularly true for stroke, which is much less well understood in terms of genetic and non-genetic determinants than IHD.2,5,6 Stroke can be investigated particularly effectively in China, as disease rates are high and widespread use of CT/MRI allows reliable determination of stroke subtypes. Better understanding of the genetic and environmental causes of disease can lead to improvements in disease prevention, risk prediction and development of new therapies. Although retrospective case-control studies suffice for studying purely genetic factors, large bloodbased prospective studies are required for studying many non-genetic causes, and many interactions. Genome-wide association studies (GWAS) in Caucasian have identified many disease correlates. However, some loci extend over hundreds of kilobases, involving several genes and many variants that are indistinguishable because of linkage disequilibrium (LD). Comparisons of GWAS data from the Chinese and Caucasian populations will provide opportunities to exploit local LD structure in different ethnic groups, leading to finer mapping of these known loci. To maximise the potential of the CKB as a comprehensive and unique biomedical research resource, we wish to undertake cohort-wide genotyping, using a custom-designed 700K SNP array (Affymetrix) optimised for Chinese populations. Newton Fund support would be used exclusively for genotyping and imputation, and will allow up to 100,000 participants to be genotyped within two years. To complete genotyping of the entire CKB cohort of 0.5 million participants, additional funding will be sought from other sources in the UK and elsewhere. Because extensive baseline information and follow-up information already exists, and planned multi-omics assays of the stored biological samples is likely to be funded from other sources, information from the proposed genotyping would create a uniquely powerful and rich resource for biomedical research over the next decade or more.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE;STROKE
Title: Measuring the impact of stroke in Sierra Leone through stroke register methodology
Funder: Medical Research Council

Abstract: I plan the following four part structure for my PhD: (1) Systematic review (2) Analysis of register data (3) Assessment of HRQL after stroke (4) Assessment of completeness of register case ascertainment. 1. The design, composition and completeness of stroke registers in Sub Saharan Africa- a systematic review Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the review will synthesise the design, composition and completeness of registers in Sub Saharan Africa. 2. What are the impacts of demographics and stroke type on the outcomes for stroke in Sierra Leone: an analysis of a prospective hospital-based stroke register Prospective hospital-based stroke register including all stroke types, that meet WHO definition of stroke. Multivariate analysis will be performed to determine odds ratios (e.g. age, gender, educational level, stroke type) for poor outcome at 90 days and one year after stroke. 3. What is the quality of life after Stroke? HRQL data from the EQ-5D-3L and survival data immediately after stroke, at 3 months and 12 months will be utilised to calculate QALYs for stroke patients. Multivariate regression analysis will examine associations of patient characteristics (gender, age, educational level), stroke severity, stroke type and functional status with health utility scores at admission and QALYs at 3 months and 12 months. Sensitivity analysis will consider the impact of alternative strategies for replacing missing data. 4. Assessing completeness and co-variates for selection bias in a hospital-based stroke register I will examine and compare descriptive statistics of three stroke datasets including demographics, stroke type and outcomes. Relative odds ratios for key variables across datasets will highlight which co-variates are involved in selection bias. Capture-recapture techniques will estimate completeness of case ascertainment.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION;8.1 ORGANISATION AND DELIVERY OF SERVICES;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE;STROKE
Title: MRF Meningococcus Genome Library
Funder: Meningitis Research Foundation

Abstract: The increase in sequencing capacity and concomitant reductions in cost make the assembly of draft sequences of large numbers of bacterial isolates practicable, with several studies of hundreds of bacterial genome sequences published recently. It is now a realistic proposal to determine the whole genomes of bacterial isolates routinely isolated for diagnostic purposes and in the near future this will be possible in real time. This project will combine advances in sequence determination and analysis approaches to determine and make publicly available the complete genome sequences for the meningococcal isolates received by the HPA MRU in the epidemiological year 2010-2011 (489 isolates). Chromosomal DNA will be prepared at the MRU and shipped to the Sanger Institute, where sequences will be determined using the Illumina platform. The short reads will be deposited in the short read archive and assembled at the University of Oxford and deposited into the PubMLST database, along with publicly releasable isolate properties and provenance data. The assemblies will be immediately available to the scientific community. Within the database, the sequences will be assigned to strain types, including designation to clonal complexes. Potential vaccine antigens variants will be identified as a priority and the entire core genome annotated for each isolate in an ongoing annotation process. Each genome sequence will also be subject to a gene discovery pipeline, enabling the members of the accessory genome to be cumulatively identified. Association studies will be conducted to associate the genetic variants identified with clinically relevant phenotypes


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Defining meningitis in UK children in the conjugate vaccine era
Funder: Meningitis Research Foundation

Abstract: Introduction in to the UK infant immunisation schedule of highly effective conjugate vaccines against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenza type b has dramatically changed the epidemiology of childhood meningitis such


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Epidemiological and economic models to assess the potential impact of immunisation against group B streptococcus (GBS)
Funder: Meningitis Research Foundation

Abstract: Group B streptococcus is an important cause of neonatal meningitis and septicaemia. Previous research has indicated that immunisation is likely to be the most cost effective strategy for reducing the GBS disease burden in infants and a new vaccine is in p


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS;3.4 VACCINES
Health categories: INFECTION
Title: Understanding the molecular epidemiology of Scottish meningococcus through genome sequencing
Funder: Meningitis Research Foundation

Abstract: Advances in genome sequencing technology which allow us to rapidly and cheaply sequence the whole genomes of organisms are revolutionising our understanding of biology. In the case of pathogenic bacteria, the insights gained from genome sequencing are off


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Point of care nucleic acid-based duplex test for detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoae (NG
Funder: Innovate UK

Abstract: The project objective is to develop a nucleic acid-based duplex test for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) for point-of-care use. The project will be carried out by a consortium, composed of Diagnostics for the Real World (Europe) Ltd. and the Diagnostics Development Unit, University of Cambridge. The expertise brought by the consortium parties covers all activities required to conduct the project: product development; scale up; validation and clinical trials in health care settings for regulatory submission. The CT/NG duplex test is based on a simple nucleic acid chemistry platform called SAMBA (“Simplified AMplification Based Assay). Simple to collect and non-invasive samples will be used, such as self-collected vaginal swabs or urine collected by FirstBurst®, a unique and patented first-void urine collection device, which collects the first 3 ml of urine containing 84% of bacteria from a urine stream. The highly stable reagents are provided in unit-dose cartridges and the results can be visually read using a patented lateral flow device. The test can be easily carried out by minimally trained personnel at point of care settings and can provide results to clinicians while the patients are still at the clinic, thus allowing immediate treatment and efficient contact tracing.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Development of a rapid multiplex Lab on a Chip system for detection of 10 STI pahtogens using Biochip Array Technology
Funder: Innovate UK

Abstract: Randox is a UK-based diagnostic company with a track record in offering innovative diagnostic solutions to healthcare providers worldwide. We are expanding into point of care diagnostics, initially with pathogen arrays, utilising our expertise multiplex detection. We require input from a partner with a history of success in disposable bio-analytical devices; the Micro Reactor Group at the University of Hull fit this requirement. Randox and University of Hull will design an integrated microfluidic chip with control and data processing instrumentation for identification of pathogens associated with sexually transmitted infection (STI). The chip will be capable of rapid extraction of DNA from a patient sample, PCR amplification, hybridisation and array detection of DNA target sequences specific to the 10 STI pathogens of interest. This automated fully integrated highly sensitive and specific screening instrumentation will perform full analysis in 30 minutes; well within the average waiting times associated with GUM clinics or GP surgeries, so one visit will provide time to collect a sample, run the test and provide any required medical intervention.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Development of an ultra-rapid, point-of care diagnostic system for Chlamydia and gonorrhoea
Funder: Innovate UK

Abstract: This project is to develop a system for ultra-rapid and highly sensitive, DNA-based Point-Of-Care tests for Chlamydia and gonorrhoea. The system will use a disposable cartridge for testing a patient sample which will be processed using a low cost reader instrument. The system will have innovative features ensuring ease of use & accuracy which include: • automated end-to-end processing of samples with no user intervention • all reagents stored on cartridge making the reader simple to use and virtually maintenance-free • a novel & sensitive electrochemical detection system allowing the reader to be small and low cost • on-board quality controls, and high multiplex capability for future menu expansion The core technology comes from research carried out at Atlas and the project combines the expertise in electrochemical assay design, reagent formulation and fluidic design at Atlas with market understanding and engineering capability at Randox Laboratories, a leading UK diagnostics company. The Health Protection Agency will provide clinical expertise, and coordinate the clinical evaluation. The project will deliver a pre-production prototype of the system fully tested in relevant clinical settings.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: A rapid cost-effective and highly sensitive point of care platform for detection of Chlamydia and Gonorrhoea
Funder: Innovate UK

Abstract: The consortium will develop a rapid, affordable, sensitive platform for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae from urine samples. The platform will be fully integrable with LIMS (laboratory information management system). This will enable rapid point of care (POC) testing within the hospital and genitourinary medicine (GUM) clinic environments. Existing rapid tests are available however these lack the sensitivity/specificity criteria achieved by laboratory based tests. The developed platform will combine the speed of the current rapid tests with the sensitivity /specificity criteria of molecular methods. The platform will provide a novel, single step, sample management system. The analysis will be based upon amplification of targeted genetic sequences and will combine both existing and novel technologies. This will provide a nucleic acid based amplification platform capable of use within a non-laboratory environment for this application and enhancing established performance criteria. The portable, battery driven analyser will incorporate high intensity/ sensitivity imaging in combination with highly efficient data interpretation. The interfaced platform will allow direct data transfer to hospital/clinic LIMS systems


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION