The key objective of this ambitious and adventurous program of research is to develop an entirely new method of spacecraft orbit transfer and orbit control using solar sails, driven only by solar radiation pressure. The new method will enable ultra-low cost libration point missions, with numerous applications in space science, Earth observation and telecommunications. To achieve this goal, orbit transfer and orbit control for such libration point missions will be investigated using modern dynamical system theory with solar radiation pressure. This provides a key advantage over conventional thrusters, since a solar sail does not require propellant, thus reducing spacecraft mass and launch costs while significantly lengthening mission duration. Through this programme of research, practical control strategies will be evaluated and engineering requirements on solar sail size and performance assessed. The programme of research will be supported by the interdisciplinary Space Glasgow Research Cluster and the host’s extensive network of international collaborators on solar sailing (ESA, NASA, NOAA). The host supervisor is the acknowledged international leader in the rapidly developing field of solar sailing. The therefore project offers a golden opportunity to link the Experienced Research’s prior work on real-world solar sail mission operations at the Japanese Space Agency (JAXA) with the host’s extensive expertise in solar sail orbital dynamics.

The Large Hadron Collider (LHC) has allowed us to make measurements of high energy particle interactions with unprecedented accuracy. Recently, previously unexplored particle masses and decays are being measured with such high precision that they are starting to show signs of disagreement with predictions from the Standard Model (SM) of particle physics. As the precision of experimental results from the LHC continues to improve, and new measurements are made, the precision of the corresponding SM predictions will need to be improved as well in order to provide a stringent test of the theory. However, many previous and current SM predictions rely on approximations which are not expected to be valid at the precision the LHC is starting to reach. Moreover, many of these decays involve composite particles; hadrons made up of two or three elementary particles called quarks. Studying these from first principles, without approximations, requires a special computational technique known as lattice quantum chromodynamics (lattice QCD). In lattice QCD, the continuous space-time of the SM is discretised onto a grid or "lattice", with quarks living on the points and gluons, the particles which carry force between the quarks, living on the lines connecting the points. The physics of the quarks can then be studied using lattices with different edge lengths (or "lattice spacings") in order to obtain results in the continuum limit at which the lattice spacing goes to zero. This technique requires the use of large supercomputing facilities, and has worked very well for studying the physics of lighter quarks, such as up, down, strange or charm quarks. Many of the signs of disagreement with theory, and hints of new physics beyond the SM, seen at the LHC are in the physics of bottom quarks. These are much heavier than up, down, strange or charm quarks and require the use of lattices with a very small lattice spacing. This is in turn much more computationally expensive and, until only very recently, doing these calculations without additional approximations remained intractable. However, advances that I have made allow for the high precision study of bottom quark decays using lattice QCD, reaching the level of accuracy required for comparison to projected LHC measurements. Utilising the new upgrade to the UK's STFC high performance computing resources, DiRAC-3, the first objective of my project is to apply these new, state of the art techniques to six different, but complementary bottom quark decays. These decays are under intense ongoing scrutiny by the experimental and theoretical physics community with upcoming measurements at the LHC. I will analyse my results for these decays, incorporating the results from the LHC, searching for hints of new physics and providing a guide for possible future measurements. The second focus of my project is the study of bottom quarks appearing in exotic particles known as "tetraquarks". These are composite particles with four quarks rather than the normal two or three that we see predominantly in nature. The LHC experiment has very recently observed both a four-charm tetraquark and a one-charm tetraquark, while a two-charm tetraquark was observed back in 2003 by the Belle experiment. It has become clear that observations of other types of tetraquark are likely to be made in the future, with compelling theoretical arguments for the existence of tetraquarks with two bottom quarks. However these have not yet been observed, no precise theoretical predictions for their masses have been made, and, furthermore, their internal structure is currently completely unknown. My aim is to make high precision predictions for the masses of these states, as well as to study their internal structure using a novel method of adding electric charge to lattice simulations.

Acute Kidney Injury (AKI) as a severe complication in hospitalized patients, a life-threatening complication that still has a high mortality. In addition, AKI is associated with high costs for intensive and prolongued treatment. To date, no early detection of AKI is possible. However, early detection is essential to initiate appropriate treatment, thereby preventing development of disease, or at least reducing the severity. Such an appproach would reduce mortality, and also costs. The proposal aims at developing a technology platform that enables early detection of AKI, based on specific proteins an peptides in urine, so-called biomarkers. These biomarkers have already been identified. For their efficient clinical application a plattform that allows accurate and fast analysis has to be developed, this development is the scope of the project. Upon successful completion of the project, a robust technology will be available that enables early detection of AKI, hence initiation of appropriate early therapeutic measures. We anticipate that as a result of this project, mortality due to AKI can be significantly decreased, and costs can be reduced.

Colorectal cancer (CRC) kills up to 170,000 Europeans annually. Although survival rates have improved gradually, new treatment strategies are certainly needed. Hyper-activation of WNT/Beta-catenin signalling occurs in up 93% of CRC cases and MYC appears to be an obligate effector of Beta-Catenin in the gut, making MYC an attractive target for therapeutic intervention. MYC, however, is difficult to target directly, owing to its lack of enzymatic activity or obviously druggable structural features. An alternative strategy is to target the biological consequences of MYC deregulation. The Murphy lab recently showed that MYC overexpressing tumour cells in culture exhibit an ectopic dependency on a little-known kinase called ARK5/NUAK1: whereas cells lacking MYC overexpression are able to withstand NUAK1 depletion or inhibition, cells with overexpressed MYC are unable to maintain energetic homeostasis in the absence of NUAK1, deplete their ATP levels, and consequently lose viability. We have therefor taken a genetic approach to examine the requirement for NUAK1 during tumour development in a genetically engineered mouse model of sporadic Beta-Catenin-driven CRC. Our preliminary results show that NUAK1 is required for CR tumour initiation and, more importantly, that NUAK1 depletion shrinks pre-existing tumours, suggesting that NUAK1 is an excellent candidate target for treatment of CRC. Based on these exciting preliminary data, I now propose to thoroughly evaluate NUAK1 as a target for therapy in CRC and to use a combination of proteomic, phosphor-proteomic and metabolomics analysis to determine the mechanism by which NUAK1 suppression erodes tumour cell viability.