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Immunocore Ltd

Immunocore Ltd

2 Projects, page 1 of 1
  • Funder: UK Research and Innovation Project Code: MR/S024220/1
    Funder Contribution: 863,858 GBP

    Background I aim to research the interaction between human immune cells (T-cells) and a specific protein (CD1c) which may play a key role when fighting tuberculosis (TB) infection. The knowledge created by this research project will help to direct future, more successful treatments for TB. TB is a lung infection that spreads by people coughing. It continues to cause disease worldwide, killing over 4,000 people every day, and is becoming progressively more resistant to the antibiotics used to treat it. New approaches to control the disease are urgently needed as standard vaccination, diagnosis and treatment have remained largely unchanged for over 40 years. A human protein called CD1c binds fatty substances on the cell surface in order for human immune cells (called T-cells) to recognise them, these T cells can then protect us from infection. CD1c can also bind substances from the bacteria that causes TB and then show them to T-cells to activate them. However, many T-cells that recognise CD1c bound to bacterial components (such as TB) also seem to recognise CD1c bound to fatty substances derived from our own cells. Currently, it is not understood how these T-cells that exhibit dual recognition of our own cells and bacteria, work within the context of human tuberculosis infection. I propose that CD1c and its T-cells regulate the interface between the TB causing bacteria and its human host and will investigate this using a range of cutting edge scientific approaches. Aims To fully understand CD1c and the role of responsive T-cells in human TB infection, I will proceed from understanding the fundamental process of how cells communicate through the binding of CD1c to its receptor and then move to studies in patients and infected cells. I will perform detailed studies at the molecular level to understand how CD1c binds and presents fatty lipid components to T-cell receptors through a combination of techniques including structural, mutational, computational, and cellular methods that will help to dissect the fundamental basis for binding of T-cells to CD1c. I will then investigate how CD1c responsive T-cells recognise fatty lipid components that are shared by human and bacterial cell walls. For this I will isolate T-cells from human blood and tissues, and investigate their reactivity to fatty components that are shared by human and bacterial cells. Finally, I will investigate the role of CD1c and its T-cells in human TB infection through employing a newly developed TB infection cell culture model using tiny 3 dimensional spheres within which human cells are infected with TB bacteria. This model is a closer representation of what happens in TB infected human lung. I will investigate the role of CD1c by modulating its expression and through manipulating the pathways that control the levels of fatty components that are produced in cells. I will also augment the infected spheres with CD1c-responsive T-cells in order to fully understand their functional impact in human TB infection. Application benefits This study will perform the first in depth investigation of the role of CD1c and its T-cells in human TB. My findings will result in new discoveries that could deliver new treatment opportunities to help tackle the TB pandemic and the basic scientific findings will also be relevant to treating cancer and inflammatory disease. This will help to keep the UK at the forefront of the research area and more importantly will help the many people affected by TB worldwide.

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  • Funder: UK Research and Innovation Project Code: EP/Y034791/1
    Funder Contribution: 9,353,240 GBP

    Synthetic Biology is a growing field of science that combines Biosciences, Chemistry, Physics, Information Technology and Engineering, and involves the redesigning end engineering of organisms for functional purposes, for example to produce valuable substances (e.g. medicines) or gain new functions (e.g. sensing and responding to something in the environment). Synthetic Biology aspires to tackle grand challenges surpassing what is possible through traditional technologies: it has wide-ranging applications in healthcare, environmental protection, energy, agriculture, computing, advanced chemicals and materials. Synthetic Biology has grown significantly in the UK over the past decade, thanks to a >£400M investment via the Synthetic Biology for Growth Programme. One of the key investments has been the SynBioCDT: the first UK CDT in Synthetic Biology funded in 2014 by the EPSRC and BBSRC and run by the Universities of Oxford, Bristol and Warwick. The SynBioCDT trained 79 excellent PhD students selected from >650 applicants, and attracted support from industrial, academic and public-facing partners. Our graduate students have gone on to work within the bioeconomy and have established disruptive start-ups. The term "Engineering Biology" has been recently adopted to highlight the essential transition of Synthetic Biology into a mature Engineering discipline. The recent UKRI National Engineering Biology Programme (NEBP) sets the UK ambition for the field and encompasses the capabilities that can support the exploitation of Engineering Biology for economic and public benefit. The Universities of Bristol and Oxford aim to establish a new CDT in Engineering Biology, the EngBioCDT, to train the academic and industrial Engineering Biology leaders of tomorrow, and to equip them with skills needed to contribute toward scalable, robust, and transformative engineering of biomimetic and biological systems. The EngBioCDT builds on our experience with the SynBioCDT and will address the NEBP requirement for a new generation of biological engineers able to translate cutting-edge science into real-world impact; it will support the EPSRC focus area 'Frontiers in Engineering and Technology'. The EngBioCDT will enable cohesive cohorts of students to gain expertise in the design, modelling and engineering of biological components and systems; to understand broad concepts ranging from biomolecular interactions to cell function; and to augment the Engineering Biology approach with robotics, automation and AI. Students will obtain advanced skills in programming and engineering; implement biological design across scales; place research in the context of both basic and applied science; and become cognisant of challenges such as process development and scale-up in biotechnology. Students will undertake both group and individual projects before starting their doctoral project. The EngBioCDT will take advantage of the expertise provided by the two Universities and our industrial partners, which will all be catalysts for inter-University and inter-sector training and research. Students will also have superb opportunities to engage with leading international academics, for example through an annual Summer School, and by participating in international conferences and workshops. The environment is exceptional. Bristol hosted BrisSynBio, one of six UKRI-funded Synthetic Biology Research Centres, and now hosts the Bristol BioDesign Institute and the Bristol Centre for Engineering Biology; the CDT Director is a EPSRC Fellow. Oxford, which led the SynBioCDT, received three fellowships and a programme grant in Engineering Biology, and offers vibrant translational opportunities. The applicants provide expertise in graduate training and many of them have previously worked together effectively. Our pool of >70 supervisors reflects the truly multidisciplinary nature of Engineering Biology, and includes internationally renowned researchers.

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