Building upon our existing flagship industry-linked EPSRC & MRC CDT in Systems Approaches to Biomedical Science (SABS), the new EPSRC CDT in Sustainable Approaches to Biomedical Science: Responsible and Reproducible Research - SABS:R^3 - will train a further five cohorts, each of 15 students, in cutting-edge systems approaches to biomedical research and, uniquely within the UK, in advanced practices in software engineering. Our renewed goal is to bring about a transformation of the research culture in computational biomedical science. Computational methods are now at the heart of biomedical research. From the simulation of the behaviour of complex systems, through the design and automation of laboratory experiments, to the analysis of both small and large-scale data, well-engineered software has proved capable of transforming biomedical science. Biomedical science is therefore dependent as never before on research software. Industries reliant on this continued innovation in biomedical science play a critical role in the UK economy. The biopharmaceutical and medical technology industrial sectors alone generate an annual turnover of over £63 billion and employ 233,000 scientists and staff. In his foreword to the 2017 Life Sciences Industrial Strategy, Sir John Bell noted that, "The global life sciences industry is expected to reach >$2 trillion in gross value by 2023... there are few, if any, sectors more important to support as part of the industrial strategy." The report identifies the need to provide training in skills in "informatics, computational, mathematical and statistics areas" as being of major concern for the life sciences industry. Over the last 9 years, the existing SABS CDT has been working with its consortium of now 22 industrial and institutional partners to meet these training needs. Over this same period, continued advances in information technology have accelerated the shift in the biomedical research landscape in an increasingly quantitative and predictive direction. As a result, computational and hence software-driven approaches now underpin all aspects of the research pipeline. In spite of this central importance, the development of research software is typically a by-product of the research process, with the research publication being the primary output. Research software is typically not made available to the research community, or even to peer reviewers, and therefore cannot be verified. Vast amounts of research time is lost (usually by PhD students with no formal training in software development) in re-implementing already-existing solutions from the literature. Even if successful, the re-implemented software is again not released to the community, and the cycle repeats. No consideration is made of the huge benefits of model verification, re-use, extension, and maintainability, nor of the implications for the reproducibility of the published research. Progress in biomedical science is thus impeded, with knock-on effects into clinical translation and knowledge transfer into industry. There is therefore an urgent need for a radically different approach. The SABS:R^3 CDT will build on the existing SABS Programme to equip a new generation of biomedical research scientists with not only the knowledge and methods necessary to take a quantitative and interdisciplinary approach, but also with advanced software engineering skills. By embedding this strong focus on sustainable and open computational methods, together with responsible and reproducible approaches, into all aspects of the new programme, our computationally-literate scientists will be equipped to act as ambassadors to bring about a transformation of biomedical research.

Have you ever wondered why your hands are the size they are? Or why some people have bigger hands, but they are almost identical in shape and proportion to your hands? The control of organ growth is highly complex, but highly important, as when the control system fails, we get overgrowth, and frequently cancer. How does the organ know when to stop growing? How does it control its shape? If we can understand this, perhaps we will be able to understand what happens when tissues over grow, and treat the problem (e.g. cancer) at its source. Many biologists have successfully used the Drosophila wing as a model to study growth control, revealing many parallels to human growth control. I hope to put all these data, the pieces of a puzzle, together, into a mathematical/computer model and eventually make a virtual wing. I‘ll be able to compare the relative importance of the different control mechanisms, something that‘s quite hard to do via experiments. I may find that internal control is key, and the environment plays little role, or vice versa. I can also model different cancerous conditions, and quickly test treatments before deciding whether they are worth trying experimentally/clinically.

The hypothesis at the root of this study is that a healthy immune system will recognise a cell when it becomes malignant and destroy it thus preventing the growth and spread of cancer. Therefore cancer can only occur when this process goes wrong. If we could find out how the immune system interacts with cancer cells and what abnormalities are occurring in this interaction we may then be able to develop strategies to improve the immune response to cancer. This would represent a potentially novel form of treatment and would be expected to improve the response to vaccination therapies that are already undergoing clinical trials in some cancers. This study will look at T cell function in blood samples from patients with leukaemia and lymphoma and then go on to look at mechanisms of improving that function in a mouse model. Finally, attempts will be made to generate a patient tumour-specific T cell response in vitro using the information gained in the earlier parts of the study. This research will be carried out by a clinical research fellow in the Institute of Cancer, Charterhouse Square, London.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Cells migrate by attaching themselves to their surroundings and generating traction forces by rearranging their internal structure. The effectiveness of these tractions depend on the relative rigidity of the cells internal structure (its cytoskeleton) and that of the surrounding material. This can be probed by measuring the elastic properties (stiffness) of a cell and how these properties vary across the cell during migration. There is some evidence that as cells transform from the normal to the cancerous state, their stifness is reduced, and as these cells become progressively more invasive the stiffness is reduced further. Thus by developing methods to probe the mechanical properties of cells we can investigate some fundamental aspects of cell biology and cancer cell biology. In this proposal we will investigate the use of ultra-high frequency acoustic imaging to study the mechanical properties of individual cells. In an acoustic microscope specimens are imaged by acoustic waves in the frequency range 100 MHz - 1 GHz. Image contrast occurs from local differences in the speed of sound, which in turn is a function of the elastic stiffness of the material being imaged. Thus, by measuring the contrast of images of cells at a range of acoustic frequencies it is possible to determine local mechanical properties with a spatial resolution of around 1 micron. However, for this technique to be applicable to the study of the biochemical and physical processes that occur during cell migration, it is necessary to further develop the technique to allow the rapid acquisition of data through images taken every few seconds. The technique will be demonstrated through the investigation of the migration of cell lines that can be controlled by altering one of the proteins used during the migration process thus allowing us to compare cells that migrate rapidly with those that are more static. We will also work in collabnoration with Cancer Research UK who will provide examples of cell lines of known invasive capability for us to characterize their mechanical properties.