Disease interception is a novel concept referring to treatment of a disease before the disease fully develops by removing altered cells. To make disease cell interception a reality we will need to overcome two key challenges. First, we will need to be able to identify few altered disease cells among many healthy ones. Second, we need to develop strategies that allow to specifically target disease cells but do not affect healthy cells. In the INTERCEPT-MDS ITN we propose to approach these challenges through research and the shared multidisciplinary and multisectorial training of 12 Early Stage Researchers (ESRs). As a result we will build and present some of Europe’s first experts in the novel field of disease cell interception. We will take advantage of single-cell omics methods that have reached a level of maturity to be applied on a broad-scale. For interception, we will explore and exploit the epigenetic regulatory space and use our privileged access to tool compounds and our capacity to perform genetic

Thrid-generation, single-molecule long-read sequencing technologies such as Nanopore and Pacbio are revolutionizing transcriptome research and are expected to outcompete short-reads sequencing for gene expression studies. However, technical and bioinformatics challenges exist to the realization of this full potential. In this project, we will train a team of excellent Doctoral Candidates to become the European and world leaders in the field of long reads transcriptome sequencing (lrRNA-seq). The team will address three fundamental aspects of current barriers to the progress that these technologies face. a) Obtaining high-quality sequencing and preprocessed data from improved library preparation protocols and bioinformatics preprocessing methods, b) Establishment of benchmarked analysis pipelines for the application of these approaches to genome annotation and isoform usage analysis both in bulk and single-cell samples, and c) Extension of long reads to multi-omics applications for the study of regulatory biology. Additionally, DC will follow an intensive and comprehensive training program composed of scientific and soft skills training, including activities related to pressing societal challenges such as climate change, diversity and inclusion, and the ethics of science. Students will complement their education through secondments in top European laboratories and Companies as well as through exposure to a network of worldwide experts in the field of RNA research.

Metabolic disorders are at pandemic levels. Based on recent estimates, ~50% of Europeans are overweight, 20% are obese and 10% have type II diabetes. Obesity and insulin resistance impact European health to the tune of €110 billion per year. These disorders have genetic, nutritional and lifestyle causes. However, the molecular mechanisms that link nutrients and lifestyle to gene activity and chromatin are poorly understood, and drug targets are only starting to be identified. Pioneering experiments by ChroMe labs now reveal how sugars, exercise, the gut microbiome and novel drugs regulate chromatin. These novel links promise to substantially improve our understanding and treatment of metabolic disorders. National governments and the EU invest major resources to address the burden of the “metabolic syndrome”. However, there is an urgent need for expert human capital able to dissect metabolic diseases, exploit new targets and establish innovative therapies. No local nor international program currently provides adequate training at this emerging interface of chromatin and metabolism. ChroMe establishes a timely and intersectorial ETN that exploits Europe’s strengths in epigenetics, physiology and medicine to translate our molecular knowledge of chromatin–metabolism interactions into therapies. Our ESRs receive advanced training in emerging technologies, bioinformatic and translational approaches, and all engage in collaborative PhD projects co-supervised by academia and industry. ChroMe’s extensive transferable skills, dissemination and public engagement program equips our ESRs with the experience and personal network needed for a career in metabolic health. By systematically involving the non-academic sector at every level in our research, training and management, ChroMe will craft future European leaders with the necessary knowledge and skills to fight the metabolic syndrome pandemic.