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Imperial College London

Country: United Kingdom

Imperial College London

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5,318 Projects, page 1 of 1,064
  • Funder: UKRI Project Code: EP/X027457/1
    Funder Contribution: 204,031 GBP

    Glycans decorate the surface of all living cells and are among the most diverse post-translational modifications. Mediating manifold interactions between cells and their environment, glycans are also heavily altered during tumorigenesis and aberrant protein glycosylation is a hallmark of cancer. The efficacy of current antibody-based reagents for diagnosis and therapy can be enhanced if target glycosylation is considered. However, our capacity to find the right target protein glycoforms is limited, and the molecular details of tumour promotion by glycans and the corresponding glycosyltransferase enzymes are ill-defined. This work will identify key factors of glycosylation-mediated breast cancer progression by profiling the glycosyltransferase isoenzymes GalNAc-T4, T6 and T14. The three enzymes are of significant relevance in several subtypes and stages of breast cancer, but their protein substrates and mechanisms of disease promotion are unclear. We will use a chemical biology strategy termed bump-and-hole engineering to develop gain-of-function reporter systems for all three isoenzymes. The strategy employs click chemistry to identify protein substrates and, by mass spectrometry (MS) glycoproteomics, glycosylation sites on these substrate proteins in an isoenzyme-specific fashion. We will use these reporter systems to profile for the first time the glycosylation sites modified by GalNAc-T4, T6 and T14 in breast cancer cell lines and primary human tissue samples in the presence of all other glycosyltransferases. We will validate our results by methods of biochemistry, cell biology and, by collaboration, in vivo mouse models of disseminated lung metastasis. We will thereby begin to understand the complexity of glycosylation especially in malignant processes. Our results will not only shed light on the details of glycan-based tumour promotion, but also inform future strategies to develop targeted diagnostics and therapeutics.

  • Funder: UKRI Project Code: MR/J007668/1
    Funder Contribution: 351,587 GBP

    Cell-cell adhesion is a key event in the life of different cell types and is essential for their organization into higher ordered structures such as blood vessels, lung, skin, muscle, etc. Conversely, de-regulation of cell-cell contacts is found following bacterial infection, would healing or initiation of tumour invasion. We are interested in understanding how cells control their ability to glue to their neighbours as opposed to scatter into surrounding tissues. We identified a molecule, Ajuba, which plays a key role to strengthen cell-cell adhesion: in the absence of Ajuba, cell-cell aggregation is greatly reduced. Our unexpected finding is that Ajuba can manipulate the function of the small GTPase Rac, which is required to stabilize cell-cell contacts. In this proposal, we will address the mechanisms via which crosstalk between Ajuba and Rac leads to stronger cell-cell adhesion. Understanding the mechanisms via which Ajuba/Rac stabilize junctions will highlight potential strategies to interfere with tumour cell invasion and metastasis. Suitable strategies to stall metastatic growth will have important implications for the quality of life of cancer patients.

  • Funder: UKRI Project Code: 2607847

    The importance of carbon capture and storage in the mitigation of climate changes arises from the potential capacity for the injection of large volumes of CO2 into suitable subsurface geologic formations. The assessment reports of the Intergovernmental Panel on Climate Change estimate that in the average of scenarios where CO2 concentration is stabilised at 450 ppm by 2100, storage demand approaches 15 Gt CO2 per year by 2050, and persists at around 20 Gt per year from 2060-2100. This represents approximately 1200 Gt CO2 stored underground by 2100. However, these modeled estimates disregard potential limitations to achieving these rates and volumes of storage from either the geographic availability of subsurface storage reservoirs, or the pressure limitations to allowable rates of injection. In this project the PhD candidate will work with experts in subsurface CO2 storage at Imperial College London, as well as the leading industry partners in developing and deploying industrial scale CO2 storage - Equinor, BP, and Shell. The PhD project will evaluate the potential for geographic and reservoir injectivity constraints to lead to bottlenecks in the development of large scale CO2 storage globally. Ultimately, we will construct models for plausible development trajectories in which constraints from geography and reservoir limitations are reflected.

  • Funder: UKRI Project Code: 1811042

    Investigation into the properties of elementary particles and the fundamental forces of nature. Precision tests of the Standard Model (SM); searches for new phenomena and extensions to the SM; studies of CP violation in the b-system; measurement of neutrino oscillation parameters; WIMP dark matter searches, preparations for future experiments, including HL-LHC, feasibility studies for future neutrino factories, double-beta decay experiments, gravitational wave detectors and linear colliders.

  • Funder: UKRI Project Code: EP/I001727/1
    Funder Contribution: 2,517 GBP

    This grant will cover the costs of organising a workshop on recent developments in N=2 supersymmetric four-dimensional gauge theories and their string duals under the gauge/string correspondence. We aim to bring together the leading international researchers in the field to present their latest results, analyse the state-of-the-art of the field, and inspire collaborations to identify and tackle the outstanding problems in this research area.One of the most important developments in modern string theory has been the discovery of dualities between gauge theories and string theories. These remarkable dualities postulate the equivalence of non-abelian gauge theories and quantum theories of gravity, as described by string theories on curved spacetimes, unravelling an unexplored connection between these two, a priori very different, types of theories at a non-perturbative level. This has given us for the first time a quantitative handle on a strongly coupled gauge theory via string theory on a curved spacetime, which tackles one of the key questions in modern theoretical physics. Perhaps the most studied example of this duality is the maximally supersymmetric (32 supersymmetries) N=4 SU(n) super Yang-Mills (SYM) theory and the dual Type IIB superstring theory on AdS_5 x S^5. This dual pair has become relatively well understood in recent years, in part because of the large amount of supersymmetry preserved and in part because of integrable structures identified on both sides of the duality. Examples of N=2 dual pairs (16 supersymmetries) are known in the literature, but are in general less well understood. At the same time, gauge theories with N=2 supersymmetry have a much richer structure than N=4 gauge theories; for example N=2 theories can have fields in different representations of the gauge group, as is the case with the Standard Model. Following the celebrated work of Seiberg and Witten, N=2 gauge theories have been viewed as a half-way house: they have both many realistic features yet one retains a good deal of control due to the supersymmtry present. As a result, a detailed understanding of general N=2 theories and their string theory duals is lightly to shed light on our understanding of non-perturbative gauge theory dynamics.Recently, a number of novel results relating to theories with 16 supersymmetries have appeared in the literature. To name just three: Firstly, Gaiotto has identified an elegant construction of very general N=2 supersymmetric gauge theories, and, together with Maldacena, found a formalism for studying their gravity duals. Secondly, a number of authors (including the PI) have been extending the integrability approach used to study the maximally supersymmetric gauge/string dual pair to less supersymmetric cases (including cases with 16 supersymmetries), suggesting that such techniques may also be relevant for gauge/string dual pairs of N=2 supersymmetric four dimensional gauge theories. Finally, building on some previous results of Nekrasov, Alday, Gaiotto and Tachikawa and later Wyllard have conjectured a relation between certain sub-sectors of N=2 supersymmetric gauge theories and Liouville and Toda theories. To summarize, we believe that over the past year or so a growing body of literature has appeared which sheds new light on gauge theories with 16 supersymmetries. This suggests that a workshop on N=2 supersymmetric four-dimensional gauge theories and their string duals would be particularly timely, and may stimulate further significant breakthroughs.

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