Recently, there has been a paradigm shift from the isolated focus on the health impact of a single behaviour (i.e. PA, sedentary behaviour or sleep) to the combination of these 24/7 movement behaviours for maximum health benefits. However, current public health guidelines are largely based on inaccurate self-report data and are, therefore, rather general (e.g. "move more and sit less"). Technological advancements have led to wearable sensor techniques providing rich time-series data over longer periods. Consequently, novel analysis methods are required to provide detailed insight into the links between multi-dimensional 24/7 movement behaviour profiles and health; which subgroups need particular attention; and what behavioural profiles are most important to target in interventions. Developing such novel analysis methods, essential for creating the evidence base needed for optimal, tailored guidelines and feedback, requires a specific combination of knowledge and skills in epidemiology, data science, method development, and public health with a thorough understanding of what is needed to translate knowledge to guidelines and improve wearable technology feedback. In LABDA, we will therefore train 10 doctoral fellows to advance this interdisciplinary field and deliver a toolbox of advanced analysis methods for sensor-based behavioural data, together with a guide for other researchers and policy makers to decide which methods to use for which (research) question.

Currently medicine tends to treat distinct diseases individually. We are increasingly aware that people do not suffer from one disease in isolation. Current treatment means that many people are taking multiple medications, which increases side-effects and can lead to harmful drug interactions. We now know that groups of diseases tend to cluster together, such that an individual with one disease is more likely to have others in the cluster. We think this is because there are underlying mechanisms which are root causes of many diseases at the same time. Age is the major risk factor for getting many diseases. Biologists have studied ageing in model organisms and humans for many years. This body of work is called Geroscience. Geroscience has now identified key mechanisms which occur in ageing and contribute to changes in physiology and health. We want to investigate how these processes relate to the development of disease clusters. By understanding the mechanisms behind the development of these disease clusters we aim to develop strategies to combat the root causes, thereby preventing or treating multiple diseases at once. Geroscience has identified three key changes which occur with ageing and contribute to health problems: cell senescence (where old cells do not die but remain in tissues secreting molecules which upset healthy cells); changes in nutrient sensing (where the cell system inappropropriately assesses the balance between growth and health), and altered autophagy (problems recycling proteins in the cells such that they accumulate and affect cell function). All three of these mechanisms have possible therapies which could be used to stop the underying process. Importantly, some of these therapies are drugs like metformin or lifestyle changes such as diet alterations which are already used in humans and known to be relatively safe. Our consortium contains internationally recognised expertise across five universities with experts from discovery science, ageing biology, computational biology, clinical trial design, and medicine who will work together to develop a new strategy for treatment. Our vision is to bring a paradigm shift in the clinical management of age-related multimorbidity, via modulation of the upstream drivers of the major disease clusters, replacing the current approach of treating diseases separately. The overarching aim of our proposal is to build a multidisciplinary collaborative to identify whether these ageing mechanisms underpin the development of distinct multimorbidity clusters. The consortium is led by doctors and will involve clinical trial experts to keep us focused on developing new treatment strategies quickly. Our plan is to use data from large cohorts which already have many biological and health measures characterised, to investigate the biology behind multimorbidity clusters. We will start with the TwinsUK cohort which has had molecular biology assayed in detail, from genes, to expression of genes, proteins, metabolites and cell subsets. In the first six-month consolidation phase, we will construct the clusters in this dataset and look at the relationships between biology and the clusters. We will also extend the team to involve additional scientific experts. In the consortium phase we will extend this to other cohorts and perform experiments on cells derived from participants and then in clinical studies to demonstrate cause and effect, and investigate how we can modify and treat multiple diseases safely (Figure 1). Combining this understanding with our collaborative's expertise in novel clinical trial designs, we will develop protocols for testing treatments targeting the identified mechanisms in people suffering from multiple diseases.

Advanced biomaterials are essential components in targeting infectious diseases and cancers, realising the potential of regenerative medicine and the medical devices of the future. A multidisciplinary team spanning Engineering, Science and Medical Faculties in Nottingham, in collaboration with 4 leading international groups has combined to realise the vision of materials discovery in 3D. Without this leap beyond 2D screening methodologies we will miss new advanced materials because they omit architecture and often poorly represent the in vivo environment. The aim is to allow us to move beyond the existing limited range of generic bioresorbable polymeric drug and cell delivery agents currently licensed for use in man and medical device polymers, to bespoke materials identified to function optimally for specific applications. We know that defining chemistry, stiffness, topography and shape can control the response of cells to materials. This programme will focus on producing and testing large libraries of these attributes in the form of patterned surfaces, particles and more complex architectures. New materials will be identified for application in the areas of targeted drug delivery, regenerative medicine and advanced materials for next generation medical devices. The 3D screening methods will define a new landscape in biomaterials discovery and create the platforms through which more effective advanced materials will be discovered. Our three ambitious application focussed areas provide high impact examples in which our biomaterials leads are developed towards exploitation in the clinic. These downstream projects will be carried out in both academic and commercial research programmes funded through partnering, licensing and formation of spin-outs as appropriate.

The hadal zone, with depths of 6000-11000 m, accounts for nearly half of the ocean's depth range, but has only recently been recognized as potential hotspot for organic carbon turnover and microbial activity. To understand the carbon mineralization and the related biogeochemical processes in hadal sediments is of global importance as carbon recycling in sediments can have critical implications for ocean chemistry, redox conditions, nutrient availability and hence for life in the oceans and on land. Due to inherent difficulties of retrieving samples for later analyses from hadal depths, a key element to make step changes in this field of research is the ability to use sensor technology to measure the important biogeochemical parameters directly in the hadal sediments and water column, i.e. without retrieving samples. The National Oceanography Centre (NOC) are world-leaders in developing autonomous miniaturized chemical sensors for use in the open ocean. Their existing technology has been tested to 6000 m depth and can measure a wide range of chemicals in environments from the polar regions to the tropics. This project will bring together NOC experts with researchers from the newly created centre of excellence for ultra-deep sea research: the Danish Center for Hadal Research (HADAL) at the University of Southern Denmark (SDU) to jointly improve our knowledge about the processes governing organic carbon degradation in deep-sea trenches. In order to achieve this, we will share resources with the HADAL Center participants, to: i) conduct a knowledge exchange and a collaborative design workshop with both partners to decide on required sensor adaptations ii) test the sensors at the HADAL pressure testing facility to depths > 6000 m to study their limitations and required improvements, and iii) develop the first proof of concept data set of nutrients measured directly in hadal sediments during joint field work to a deep-sea trench off Japan. The outcomes of this project will answer exciting research questions about organic carbon degradation processes in deep-sea trenches and their impact on the surrounding ecosystem and will provide a proof-of-concept data set that will position us to strengthen the collaboration by writing joint proposals for future collaborations.

This project examines how the current changes in the political information environments in European democracies affect the conditions for a healthy democracy. As a theoretical background we employ the concept of ‘political information environment’ (PIE) that includes both the supply and demand of political news and information. Supply refers to the quantity and quality of news and public affairs content provided through traditional and new media sources, demand captures the amount and type of news and information the public wants or consumes. Recent changes in the political information environment may lead to a growing number of uniformed, misinformed and selectively informed citizens, potentially endangering the functioning of democracy. To examine these concerns, the study aims at investigating the following: (1) how do citizens today gain political information and how does this relate to their political attitudes and behaviour; (2) what is the content and quality of the information citizens are exposed to; (3) where do divides between being informed and not being informed exist, across and within European societies, and (4) how can citizens be empowered to navigate and find valuable information. We will do this through a series of comparative, innovatively designed studies, including web tracking, comparative surveys, focus groups and survey-embedded experiments in 14 European countries and the US. These countries vary on a number of key contextual factors relevant for the study, covering both “young” and established democracies with different democratic traditions, media systems, and news consumption habits.