Marie-Curie training network grant ‘EndoConnect’ awarded to Bart van de Sluis: 4 million euros for European Research Training

European Research Training in Understanding the Molecular Regulation and the Role of Endo-Lysosomal Processes in Cardio-Metabolic Diseases.

Metabolic syndrome (MetS) is a collection of pathological conditions including abdominal obesity, increased blood pressure, insulin resistance and increased blood glucose and lipids. MetS is a multiplex risk factor for type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). Combined, these cardio-metabolic diseases account for almost 40% of all death worldwide every year (the World Health Organization, WHO), and thus form a heavy burden on our society and health care system.

The endo-lysosomal system (a part of intracellular compartments and transport vesicle pathways) is essential to acquire lipids and nutrients according to the need of the cell and, subsequently, to maintain metabolic homeostasis. The strong connection between the endo-lysosomal system and metabolism is reflected in the observations that defects in this system are correlated with cardio-metabolic disorders, such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease. The molecular mechanisms that interconnect the endo-lysosomal system with metabolism are, however, poorly understood. This can be largely explained by the fact that (1) endo-lysosomal and metabolic research are carried out independent of each other and (2) the number of model systems to study endo-lysosomal processes at an organismal and clinical level are limited.

It is the ambition of EndoConnect to change this by bringing top scientists and industrial partners from different European countries (the Netherlands, Germany, UK, Finland, Spain, Switzerland) together to train PhD students in interdisciplinary research, with the focus on translating key findings from cellular and animal models to patients with cardio-metabolic diseases. It is our mission to:

(1) understand the molecular organization and regulation of endo-lysosomal processes,

(2) elucidate how metabolism and endo-lysosomal processes are intertwined,

(3) understand how defects in the endo-lysosomal system contribute to the development of cardio-metabolic diseases and, finally,

(4) how the endo-lysosomal system contributes to the efficiency of therapeutics.

EndoConnect will provide an international training program for PhD students to acquire knowledge and state-of-the-art scientific, technical, and transferable skills to connect molecular and cell biology research with physiology and biomedical research towards translation. This training will significantly increase the career perspectives of PhDs and allow them to become the future leaders in this emerging interdisciplinary field, both in a scientific and societal manner. In addition, we expect that EndoConnect will increase our understanding of the molecular interrelation of the endo-lysosomal system with cardio-metabolic diseases, which will pave the road for novel diagnostics and therapeutics.

EndoConnect coordinator Bart van de Sluis (1973) has been trained as a Molecular Geneticist at the University of Utrecht. A part of his research group focuses on unravelling the mechanism by which the endosomal sorting machinery keeps the levels of plasma lipid levels under control, and hereby the risk of cardiovascular disease. Together with EndoConnect partner Jan Albert Kuivenhoven (UMCG), he uses this knowledge to understand the underlying mechanisms of dyslipidemia in patients.

We hope to recruit the PhD students and launch our EndoConnect website soon.

• https://www.umcg.nl/NL/UMCG/Nieuws/Persberichten/Paginas/20-miljoen-euro-voor-vijf-grote-onderzoeksprojecten-umcg.aspx

• https://ec.europa.eu/research/mariecurieactions/news/ITN-2020-call-results