The stated goal of RHAPSODY is to define a molecular taxonomy of type 2 diabetes mellitus (T2D) that will support patient segmentation, inform clinical trial design, and the establishment of regulatory paths for the adoption of novel strategies for diabetes prevention and treatment. To address these goals, RHAPSODY will bring together prominent European experts, including the leaders of the diabetes-relevant IMI1 projects to identify, validate and characterize causal biomarkers for T2D subtypes and progression. Our plans are built upon: (a) access to large European cohorts with comprehensive genetic analyses and rich longitudinal clinical and biochemical data and samples; (b) detailed multi-omic maps of key T2D-relevant tissues and organs; (c) large expertise in the development and use of novel genetic, epigenetic, biochemical and physiological experimental approaches; (d) the ability to combine existing and novel data sets through effective data federation and use of these datasets in systems biology approaches towards precision medicine; and (e) expertise in regulatory approval, health economics and patient engagement. These activities will lead to the discovery of novel biomarkers for improved T2D taxonomy, to support development of pharmaceutical activities, and for use in precision medicine to improve health in Europe and worldwide.

Reducing carbon emissions and securing energy supplies are crucial international goals to which energy demand reduction must make a major contribution. On a national level, demand reduction, deployment of new and renewable energy technologies, and decarbonisation of the energy supply are essential if the UK is to meet its legally binding carbon reduction targets. As a result, this area is an important theme within the EPSRC's strategic plan, but one that suffers from historical underinvestment and a serious shortage of appropriately skilled researchers. Major energy demand reductions are required within the working lifetime of Doctoral Training Centre (DTC) graduates, i.e. by 2050. Students will thus have to be capable of identifying and undertaking research that will have an impact within their 35 year post-doctoral career. The challenges will be exacerbated as our population ages, as climate change advances and as fuel prices rise: successful demand reduction requires both detailed technical knowledge and multi-disciplinary skills. The DTC will therefore span the interfaces between traditional disciplines to develop a training programme that teaches the context and process-bound problems of technology deployment, along with the communication and leadership skills needed to initiate real change within the tight time scale required. It will be jointly operated by University College London (UCL) and Loughborough University (LU); two world-class centres of energy research. Through the cross-faculty Energy Institute at UCL and Sustainability Research School at LU, over 80 academics have been identified who are able and willing to supervise DTC students. These experts span the full range of necessary disciplines from science and engineering to ergonomics and design, psychology and sociology through to economics and politics. The reputation of the universities will enable them to attract the very best students to this research area.The DTC will begin with a 1 year joint MRes programme followed by a 3 year PhD programme including a placement abroad and the opportunity for each DTC student to employ an undergraduate intern to assist them. Students will be trained in communication methods and alternative forms of public engagement. They will thus understand the energy challenges faced by the UK, appreciate the international energy landscape, develop people-management and communication skills, and so acquire the competence to make a tangible impact. An annual colloquium will be the focal point of the DTC year acting as a show-case and major mechanism for connection to the wider stakeholder community.The DTC will be led by internationally eminent academics (Prof Robert Lowe, Director, and Prof Kevin J Lomas, Deputy Director), together they have over 50 years of experience in this sector. They will be supported by a management structure headed by an Advisory Board chaired by Pascal Terrien, Director of the European Centre and Laboratories for Energy Efficiency Research and responsible for the Demand Reduction programme of the UK Energy Technology Institute. This will help secure the international, industrial and UK research linkages of the DTC.Students will receive a stipend that is competitive with other DTCs in the energy arena and, for work in certain areas, further enhancement from industrial sponsors. They will have a personal annual research allowance, an excellent research environment and access to resources. Both Universities are committed to energy research at the highest level, and each has invested over 3.2M in academic appointments, infrastructure development and other support, specifically to the energy demand reduction area. Each university will match the EPSRC funded studentships one-for-one, with funding from other sources. This DTC will therefore train at least 100 students over its 8 year life.

The European Regimen Accelerator for Tuberculosis (ERA4TB) has the explicit goal of developing a new combination therapy to treat all forms of TB starting from ~20 leads and drug candidates provided by EFPIA. Since details of these are as yet unavailable, we will implement an agile drug development algorithm that entails profiling and portfolio construction. Profiling involves characterisation and ranking molecules in preclinical studies comprising in vitro drug combination assays, hollow fiber and single cell analysis, innovative murine and non-human primate models, PK/PD studies, combined with biomarker discovery and non-invasive NIR or PET/CT imaging to monitor disease progression and response to treatment. Modelling, simulation and artificial intelligence tools will help progress compounds from early preclinical to clinical development and to predict drug exposure, human doses and the best combinations. After extensive preclinical profiling, selected compounds will enter portfolio development for first time in human tests and phase I clinical trials in order to ensure that they are safe, well-tolerated and bioavailable with negligible drug-drug interactions. If needed, formulation studies will be conducted to improve pharmacological properties. ERA4TB has assembled the best expertise and resources available in Europe, to build a highly effective and sustainable drug development consortium with a flexible and dynamic management system to execute the profiling and portfolio strategy, aided by clearly defined go/no-go decision points. The expected outcome of ERA4TB is a series of highly active, bactericidal, orally available drugs to constitute two or more new combination regimens with treatment-shortening potential ready for Phase II clinical evaluation. These regimens will be compatible with drugs used to treat common comorbidities, such as HIV-AIDS and diabetes, and should impact UN Sustainable Development Goal 3, namely, ending TB by 2030.

Antiviral drugs will be key in the management of future virus outbreaks. For each virus family with epidemic/pandemic potential, stockpiles of potent drugs are needed that can be deployed when a new pathogen emerges. Such broader-acting drugs (targeting conserved viral functions) are needed as of “day one” of an outbreak, for treatment and prophylaxis (e.g., in HCW and frail patients). In combination with quarantine measures, such drugs will delay (global) spread, allowing time for vaccine-development. Since the 2003 SARS outbreak, PANVIPREP’s core partners have successfully collaborated in leading European antiviral drug research projects. This provides a solid scientific basis in combination with translational drug discovery expertise. The team includes virologists, biochemists, structural biologists, medicinal chemists and pharmacokinetics experts. Previously developed know-how and toolboxes will be a major asset to achieve immediate impact. PANVIPREP aims to greatly expand the antiviral portfolio and identify novel druggable targets of high-risk RNA viruses. Hits will be identified through (i) phenotypic antiviral screening of compound libraries (ii) structure-based drug design, (iii) in silico screening, supported by the latest machine-learning methods. We will deliver 25 to 50 high-quality, broad(er)-spectrum (pan-genus/pan-family) hit molecules/hit series. Two of these will be developed to the early lead stage, including proof of concept in animal infection models. Remaining hits will serve as chemical tool-compounds to explore mechanisms of action thereby identifying novel druggable targets in RNA virus replication. This in turn will accelerate target-based drug design efforts. The workflow will integrate best practices in antiviral drug discovery with a range of methodological innovations, including AI-based methods, thus renovating and accelerating the antiviral hit discovery pipeline future use and contributing to pandemic preparedness.