Periodic Reporting for period 1 - PoLiMeR (Polymers in the Liver: Metabolism and Regulation)
Periodo di rendicontazione: 2018-10-01 al 2020-09-30
PoLiMeR: Polymers in the Liver – Metabolism and Regulation
The PoLiMeR consortium is a Systems Medicing training network for young scientists of various disciplines and nationalities. We believe that the present day challenge to provide innovative therapies for a wide range of metabolic diseases requires strong international collaboration between experts from different scientific fields and sectors. Therefore, PoLiMeR trains 15 PhD students in different aspects of Systems Medicine, including computational, laboratory, and clinical aspects of metabolic diseases. The students carry our their research projects in 13 universities, small companies, and university hospitals in 7 European countries. Our PhD students come from all over the globe, from Europe, Asia, Africa and South America.
Our scientific focus is on the inherited metabolic diseases of carbohydrate and fat metabolism. Although individually rare (typically affecting less than 1 in 2000 people), together the over 800 different inherited metabolic diseases have a serious impact on European health. Children, often suffering from severe and life-threatening symptoms, account for 68% of the patients. The wide variety of metabolic diseases dilutes the research efforts. Moreover, it becomes increasingly clear that individual differences with respect to history, lifestyle, and genetic make-up affect disease progression and treatment response.
The aims of the PoLiMeR consortium are to:
1. Train a new generation of PhD students in the computational, laboratory, and clinical aspects of Systems Medicine, to collaborate across boundaries of countries, scientific discipline, and sectors.
2. Develop a Systems Medicine approach for the inherited diseases of carbohydrate and fat metabolism in the liver. These should lead to innovative diagnostic tools and treatments and be more widely applicable to other diseases.
The PoLiMeR consortium is a Systems Medicing training network for young scientists of various disciplines and nationalities. We believe that the present day challenge to provide innovative therapies for a wide range of metabolic diseases requires strong international collaboration between experts from different scientific fields and sectors. Therefore, PoLiMeR trains 15 PhD students in different aspects of Systems Medicine, including computational, laboratory, and clinical aspects of metabolic diseases. The students carry our their research projects in 13 universities, small companies, and university hospitals in 7 European countries. Our PhD students come from all over the globe, from Europe, Asia, Africa and South America.
Our scientific focus is on the inherited metabolic diseases of carbohydrate and fat metabolism. Although individually rare (typically affecting less than 1 in 2000 people), together the over 800 different inherited metabolic diseases have a serious impact on European health. Children, often suffering from severe and life-threatening symptoms, account for 68% of the patients. The wide variety of metabolic diseases dilutes the research efforts. Moreover, it becomes increasingly clear that individual differences with respect to history, lifestyle, and genetic make-up affect disease progression and treatment response.
The aims of the PoLiMeR consortium are to:
1. Train a new generation of PhD students in the computational, laboratory, and clinical aspects of Systems Medicine, to collaborate across boundaries of countries, scientific discipline, and sectors.
2. Develop a Systems Medicine approach for the inherited diseases of carbohydrate and fat metabolism in the liver. These should lead to innovative diagnostic tools and treatments and be more widely applicable to other diseases.
Our Systems Medicine approach is based on the idea that generalized computational and cell models can be adapted to study patient-specific responses. In essence, liver metabolism is largely the same in different people. However, history, lifestyle and genetic make-up may cause differences in the amounts and quality of metabolic enzymes and the way in which they interact. These enzymes are the core machinery for all metabolic processes in the liver. Experimental analysis of enzyme concentrations and activities, and of their impact on metabolite concentrations and metabolic rates, provides the data to make generic computational models specific for individual patients. Moreover, patient-specific responses of liver metabolism can also be studied in an experimental liver-on-chip model. If the liver-on-chip exhibits the key metabolic processes that take place in a real liver, then it can be seeded with patient cells, in order to study patient-specific liver functions in the laboratory. Innovative computational and experimental disease models, together with novel methods to analyse metabolites and enzyme function in small samples, will allow a better understanding of disease processes in the liver and the response to putative therapy, without the need for invasive biopsies in children.
The PoLiMeR training programme consists of different components. All PhD students have a research project in their specific field of expertise, in which they collaborate between different expertise and institutes. As part of their training they visit each other’s institutes for short and long internships. Due to the Covid-19 pandemic we had to postpone the longer internships. However, we continue the collaborations online and via exchanges of models and samples. Furthermore, the training comprises advanced scientific courses, during which the principle investigators share their knowledge on the different aspects of Systems Medicine and inheritited metabolic diseases. Until now, the courses included hands-on experimental and computational practice, as well a meeting with a patient. Finally, the PoLiMeR PhD students receive complementary skills training, focusing on data management, communication, grant writing and entrepreurship. Until now, we completed four training weeks, two on site in Heidelberg and Groningen, while those in Leiden and Manchester were online.
In their research projects the PhD students collaborate in interdisciplinary teams that tackle fundamental challenges in the metabolism of carbohydrates and fats. Each of these challenges is related to the fact that carbohydrates and fats are large molecules and often do not follow the classical paradigms. For instance, enzymes that convert small molecules are typically highly specific for certain small molecules that fit exactly in the enzyme structure. In contrast, enzymes that convert large molecules such as fat and glycogen, need to be promiscuous. Moreover, the aberrant glycolygen structures that we observe in inherited glycogen storage diseases, interact in a different way with the enzymes. This has an impact on the availability of energy for the patient. We investigate these, and other challenges posed by fat and carbohydrate metabolism, in teams of computational, experimental, and clinical experts.
The PoLiMeR training programme consists of different components. All PhD students have a research project in their specific field of expertise, in which they collaborate between different expertise and institutes. As part of their training they visit each other’s institutes for short and long internships. Due to the Covid-19 pandemic we had to postpone the longer internships. However, we continue the collaborations online and via exchanges of models and samples. Furthermore, the training comprises advanced scientific courses, during which the principle investigators share their knowledge on the different aspects of Systems Medicine and inheritited metabolic diseases. Until now, the courses included hands-on experimental and computational practice, as well a meeting with a patient. Finally, the PoLiMeR PhD students receive complementary skills training, focusing on data management, communication, grant writing and entrepreurship. Until now, we completed four training weeks, two on site in Heidelberg and Groningen, while those in Leiden and Manchester were online.
In their research projects the PhD students collaborate in interdisciplinary teams that tackle fundamental challenges in the metabolism of carbohydrates and fats. Each of these challenges is related to the fact that carbohydrates and fats are large molecules and often do not follow the classical paradigms. For instance, enzymes that convert small molecules are typically highly specific for certain small molecules that fit exactly in the enzyme structure. In contrast, enzymes that convert large molecules such as fat and glycogen, need to be promiscuous. Moreover, the aberrant glycolygen structures that we observe in inherited glycogen storage diseases, interact in a different way with the enzymes. This has an impact on the availability of energy for the patient. We investigate these, and other challenges posed by fat and carbohydrate metabolism, in teams of computational, experimental, and clinical experts.
The PoLiMeR PhD students are well on their way to become Systems Medicine experts. They have presented their research on scientific conferences and to the general public. We anticipate that their results will contribute to better diagnosis and treatment of inherited metabolic diseases. After their PhD they should be able to apply their skills and knowledge to a wide variety of biomedical problems, in industrial, clinical, or academic environments.