The Transformative Imaging for Quantitative Biology (TIQBio) partnership aims to develop disruptive technology for the benefit of UK Plc and for solving problems in industry and academia. The mainstay of current imaging methods to look at pre-clinical biological samples is fluorescence microscopy. This technique relies on the use of tags, which emit light when illuminated by the microscope, allowing the location of the structures or molecules to which they are attached to be determined. Insertion or attachment of a tag is an invasive process for any living system and can alter its behaviour and the way it functions. Furthermore, all living systems, tissue and cells are inherently 3-dimensional. Therefore to image in 3D one has to point-by-point collect fluorescence signal and reconstruct an image. This is a very slow and damaging process especially for 3-D live samples that represent real-life conditions. For discovering new drugs or for studying mechanisms in diseases or healing it is obvious that one should use conditions that are as near to real life as possible, before human testing. This is why most biomedical researchers and industrial sectors that operate in the area of diseases, drugs or therapeutics want to use life-like samples. At the moment however, the tools to image them in 3D and in an unperturbed, non-damaging manner simply do not exist. Furthermore, it is desirable to work at the highest resolution so we can see the smallest things that exist at the nanoscale in such biological systems and obtain holistic information about the chemical composition and structural order. This information will reveal unprecedented insight and hence help understand diseases or why a particular drug candidate does or does not work allowing better ones to be made. TIQBio will address these challenges so that unperturbed, live imaging can be carried out at an unprecedented resolution level in full 3D, with holistic information from multiple readouts carried out rapidly on 100s of test biological models. These innovative tools and technologies will allow the discovery of drugs to be improved, reduce costs for bringing a drug to market benefiting the pharma industry and patients alike. Patients with rare diseases or in lower income countries may gain access to new drugs because of the proposed disruptive technology. Biomedical researchers will benefit as they will be able to understand phenomena without misleading results due to tags; the use of real life-like models will better inform or protect the public through the development of therapies or defence countermeasures.

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.

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.

Every chemical element is special, but some elements are more special than others! Carbon, the sixth element of the periodic table, is unique with respect to its versatility and impact on our lives. Carbon is the foundational element of all organic molecules including for example, materials, pharmaceuticals and fuels. No other element has shaped the world around us more than carbon. For this reason, the development of innovative methods to link carbon atoms together in desirable structures is of tremendous importance and is an overarching ambition in the field of organic chemistry. An important example of a reaction that can be used to link carbon atoms together is the Diels-Alder reaction, which since its discovery has been used to construct the complex carbon skeletons of numerous important molecules including pharmaceuticals, vitamins, hormones, agrochemicals and a raft of fragrance and flavour compounds. Historically, the Diels-Alder reaction has been performed using either chemical catalysts or high temperatures and pressures. Unfortunately, these approaches can give a mixture of products and have detrimental sustainability issues (use of energy and metal catalysts). However, biological catalysts for this reaction, so called 'Diels-Alderases', offer an attractive alternative, circumventing many of the complexities associated with chemical catalysis, and thus enabling Diels-Alder reactions to be performed under ambient conditions, with exquisite regio- and stereochemical control, and in an inherently 'greener' way. In this academic-industrial project, which builds on a strong foundation of interdisciplinary collaborative research by the applicants in the study of natural Diels-Alderases, the researchers will: i) Develop flow systems using immobilised enzymes to catalyse Diels-Alder reactions on gram scales; ii) investigate the ability of natural Diels-Alderases and rationally-engineered variants to catalyse both intramolecular (with both reactive groups within the same molecule) and intermolecular (with reactive groups in different molecules) cycloaddition reactions; iii) study hitherto uncharacterised natural Diels-Alderases and their associated natural products from cryptic biosynthetic gene clusters; iv) Deploy our portfolio of natural and engineered Diels-Alderases, in combination with auxiliary enzymes, to undertake chemoenzymatic total syntheses of high-value target compounds.

Moore's Law states that the number of active components on an microchip doubles every 18 months. Variants of this Law can be applied to many measures of computer performance, such as memory and hard disk capacity, and to reductions in the cost of computations. Remarkably, Moore's Law has applied for over 50 years during which time computer speeds have increased by a factor of more than 1 billion! This remarkable rise of computational power has affected all of our lives in profound ways, through the widespread usage of computers, the internet and portable electronic devices, such as smartphones and tablets. Unfortunately, Moore's Law is not a fundamental law of nature, and sustaining this extraordinary rate of progress requires continuous hard work and investment in new technologies most of which relate to advances in our understanding and ability to control the properties of materials. Computer software plays an important role in enhancing computational performance and in many cases it has been found that for every factor of 10 increase in computational performance achieved by faster hardware, improved software has further increased computational performance by a factor of 100. Furthermore, improved software is also essential for extending the range of physical properties and processes which can be studied computationally. Our EPSRC Centre for Doctoral Training in Computational Methods for Materials Science aims to provide training in numerical methods and modern software development techniques so that the students in the CDT are capable of developing innovative new software which can be used, for instance, to help design new materials and understand the complex processes that occur in materials. The UK, and in particular Cambridge, has been a pioneer in both software and hardware since the earliest programmable computers, and through this strategic investment we aim to ensure that this lead is sustained well into the future.