NUCLEAR aims at educating future experts that can drive the emerging field of Metabolic Regulation of Genome Function and Cell Identity relevant for stem cell biology and cancer. It is a Doctoral Training Network composed of 14 beneficiaries and 12 partner organisations including three industrial partners, a training-oriented foundation, a patient support association from 8 EU member states, 1 associated country and a non-EU member state self-funding itself to the level of beneficiary. Given the highly interdisciplinary nature of this emerging field, no single institution can provide all suitable infrastructures and the know-how required for high-quality PhD-level training. To address this shortfall in training capacity, NUCLEAR brings together European leaders in metabolomics, functional genomics, chromatin regulation, stem cell biology and cancer with innovators in precision nutrition, mass spectrometry technologies and drug development. Together we are committed to the following: 1. To train 16 doctoral candidates (DCs) through an innovative program structured in four capacity axes and occurring on three complementary levels to deliver enabling scientific and transferable skills. 2. To guide DCs in collaborative research bridging boundaries of countries, sectors, and disciplines. 3. To address three key challenges that limit the advancement and exploitation of the field and that are the lack of tools to measure nuclear metabolism, the lack of understanding of underlying molecular mechanisms and the lack of targets for novel cancer therapies. 4. To build lasting infrastructures for dissemination, communication and exploitation promoting an entrepreneurial culture and maximizing and extending the impact of this proposal beyond its lifetime. 5. To increase the international visibility of European research by taking leadership in the emerging field of Metabolic Regulation of Genome Functions and Cell Identity.

Metabolic disorders are a major burden on the European population and health care systems. Moreover, metabolic perturbations contribute substantially to other pathologies such as neurodegenerative disorders and cancer. The causes of metabolic dysregulation are manifold and lead to pathological shifts, often in response to imbalanced nutrition. Likewise, changes in metabolism affect signalling mechanisms and gene regulation, aggravating the pathology. The mechanisms of this interdependence between metabolism and signalling are still not well understood. HubMOL will fill this knowledge gap and open new horizons by exploring the functional duality of a set of small molecules that are involved in all cellular functions - the Hub Molecules Of Life (HubMOLs) including ATP, SAM (S-adenosylmethionine) and the vitamin-derived cofactors, NAD, FAD, and CoA. They are key components of both metabolism and signalling networks and are interconnected, for example, through their participation in posttranslational protein modifications (PTMs). The complexity of this emerging area requires interdisciplinary scientists equipped with comprehensive competences covering experimental, computational and systems biology as well as clinical medicine. Therefore, the main HubMOL goal is to provide world-class training in these areas to 16 DCs enabling them to establish fundamentally new insights into cofactor biology and lay the ground for patient-tailored vitamin supplementation concepts. The strategic exposure of the 16 young researchers to leading European academic institutions, companies and clinical environments combined with systematic training in entrepreneurship and transferable skills will strongly improve their employability for positions in both private and public sectors. HubMOL will impact patients and society by developing therapies for metabolic and regulatory imbalances based on hub molecule biology.