'CoolBlue is a highly innovative project with a goal to develop next generation GaN laser technology for implementation in quantum sensors based on atomic cooling. Conventional laser sources for these applications are complex and inefficient whereas a direct blue laser diode source could offer many advantages such as increased power, lower complexity, and smaller size, potentially transforming quantum sensors such as frequency standards from laboratory instruments into miniaturised, robust devices. The project will consist of two cycles of laser design, fabrication and test, in which we will optimise key laser parameters including linewidth and power. The project will be led by CSTG Ltd in partnership with the University of Glasgow and Aston University.'

Bone cancer typically occurs in children and young adults. Current treatments involve removal of the tumorous area followed by chemotherapy. Following surgery a large bone defect is present due to the removal of the tumour and care must be taken to ensure that the cancer does not return. If the cancer reoccurs at the primary site then survival rates drop significantly. Currently these two key factors, repairing the bone defect and preventing tumour reoccurrence, are treated as two different problems. A common treatment and the ability to treat the cancer promptly can lead to a better clinical outcome and thus, there is an urgent need to develop new therapeutic strategies based on the use of third-generation biomaterials that can simultaneously target cancer cells, prevent further reoccurrence, and stimulate the regeneration of damaged tissue. Bioactive glasses containing gallium hold great potential for this purpose as has been shown in previous studies undertaken in our laboratory. These materials display remarkable osteoconductive and osteoinductive properties and can be tailored to carry therapeutic ions such as gallium, zinc, and cobalt, to name a few. Furthermore, bone is after blood the most transplanted tissue worldwide and bioactive glasses are seen as some of the most promising materials to replace conventional surgical reconstruction procedures such as prostheses, orthopaedic implants, allografts, and autografts. Gallium is a metal ion widely used for cancer treatment due to its ability to inhibit tumour growth. It shares certain chemical properties with iron that enable it to bind to transferrin, a cellular ion receptor. Since iron plays a critical role in cell function, the intake of gallium disrupts the ion homeostasis within the cell leading to cell apoptosis. Cancer cells exhibit an increased dependence on iron compared with healthy cells which can be harnessed to develop novel strategies for cancer treatment using gallium. The inhibitory effects of gallium on malignant cells not only depend on the dose delivered, but also on the duration of exposure. Therefore, the release of ions needs to be strictly controlled in order to enhance their therapeutic effect and avoid adverse cell behaviour. Bioactive glasses are excellent carriers for bioactive molecules and therapeutic drugs as their degradation rate can be tailored by modifying their molecular structure. In addition, when bioactive glasses dissolve their basic components form a mineral layer that greatly enhances bone regeneration as it mimics the innate structure of bone, providing a framework for new tissue and blood vessels to grow into. However, ossification is a process that involves several stages from the osteogenic differentiation of stem cells to the formation of bone-like structures known as bone nodules. A large part of the current literature with regards to bone tissue engineering claims to generate bone using bioactive glasses though the characterisation methods used to prove these claims fall short. Gallium bioactive glasses have generally been studied for their antibacterial properties, but little research has been made on their potential clinical applications for bone cancer. This project will build on previous studies that successfully inhibit cell proliferation of osteosarcoma cells in vitro using silica-based bioactive glasses containing gallium. The overall project aim will be to synthesise bioactive glasses containing different concentrations of gallium, investigate their effects on different cell lines and optimise them to target bone cancer cell lines while promoting healthy cell proliferation. The ability of these bioactive glasses to form bone structures will also be thoroughly examined.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

G protein coupled receptors (GPCRs) are the largest family of proteins in the human genome and also the largest target for therapeutic drugs; thus they are of enormous scientific and practical interest. They are divided into a number of families. Of these, family-A is the best understood, but family-B includes receptors which are likely to be important in many disease states and so it is important to understand how these function, both to further our knowledge of fundamental biology and also for the design of new drugs. Calcitonin gene-related peptide (CGRP) is found throughout the nervous system and is particularly important in regulating both the cardiovascular system (the heart and blood vessels) and also the immune system and inflammation. The receptor for CGRP is of special scientific interest as it involves a GPCR called CLR and also a second protein called RAMP1. RAMP1 is a member of a protein family that modulates a number of GPCRs of which the best characterised is CLR. CGRP is also likely to be important both in cardiovascular disorders and any disease that involves inflammation. The peptide is a major cause of migraine and drugs which block CGRP receptors have shown great promise in clinical trials; however, so far it has not been possible to use these clinically because of toxicity problems. Thus, there is an urgent need to develop new drugs that could act on CGRP receptors. The CGRP receptor is made up of two parts. A portion called the transmembrane domain is found in the membranes of cells. This is connected to the extracellular domain, which is on the outside of cells. CGRP interacts with both parts of this structure and causes the transmembrane domain to change shape. This causes the receptor to interact with other proteins, leading to cell activation. We have a crystal structure of the part of the CGRP receptor that is on the outside of cells. Unfortunately, we do not know how CGRP binds to this, nor do we know how it binds to the transmembrane domain. This severely limits our understanding of the receptor and our ability to design drugs that could target it. We have previously used experimental data from a technique known as site-directed mutagenesis to construct a computer model of the transmembrane domain of the CGRP receptor. This transmembrane domain is very similar to the transmembrane domains of two family-B GPCRs which were crystallised after our computer model was produced. This gives us confidence that our approach of combining experimental and computational methods is valuable. In this project, we intend to extend the approach to study how CGRP binds to both domains of the receptor and how this causes the receptor to become activated. We will use mutagenesis and also methods where we physically cross-link CGRP to the receptor to identify contact points. We will then use these to construct computational models, which we can refine through further experimentation. Using a computer, we can predict how the receptor shape will change when CGRP binds to it, so identifying the mechanism for receptor activation. This knowledge will be benefitial in the design of new drugs which can either block the receptor or promote its activation.