Complex Systems

Diabetes Research

Role of the microbiome in development of islet autoimmunity

Islet autoimmunity is usually a predecessor of type 1 diabetes and has been shown to often develop within the first years of life. There is increasing evidence that the process of shaping the immune response is closely related to the establishment of a stable ecosystem consisting of a human host and a large cohort of accompanying bacteria. Our aim is to understand the influence of environmental factors (e.g. diet) on the gut microbiome and to understand how interactions between the gut microbiome and the host metabolism are related to the development of autoimmunity and type 1 diabetes. We develop methods and apply algorithms to estimate interaction networks describing the complex interplay between bacteria in the gut and we compare networks of children who developed autoimmunity to networks of children who did not develop autoimmunity. Furthermore, we use algorithms to detect clique-like microbial communities and analyse the determinants of these communities by incorporating secondary variables like treatment with antibiotics, type of birth, breast feeding and the age children were first fed solid food. 

Source: HMGU

Funding:

 JDRF

Modeling of antibody characteristics in islet autoimmunity

Most individuals who generate type 1 diabetes associated islet autoantibodies also develop type 1 diabetes within some years. However, this is not always the case and individuals who develop multiple autoantibodies have a higher type 1 diabetes risk than individuals that develop single autoantibodies. A better understanding of different autoantibody profiles may provide a possibility for the early diagnosis and treatment of type 1 diabetes. We developed an unsupervised clustering algorithm for the detection of similar time dependent profiles of autoantibodies associated with the development of type 1 diabetes. The clustered profiles are used to associate different antibody profiles with the development of type 1 diabetes, genetic risk factors and secondary variables like the type of birth.

 

Source: HMGU

 Partner:

Modeling the interplay of glucose, insulin and ß-cell growth

Recent experimental results indicate the relevance of the ß-cell cycle in promotion as well as compensation processes during the development of diabetes mellitus. We investigate the dynamics of the interplay of glucose, insulin and the ß-cell cycle based on a mathematical model of ordinary differential equations additionally including integral terms. To examine the metabolic system in a pathological situation - diabetes mellitus - we first model the physiological case. In a second step the model will be adapted to simulate either type 1 or type 2 diabetes.

The model includes the interaction of the ß-cell cycle with different key processes in the insulin storage and secretion by the ß-cells. The aim is an improved comprehensive understanding of the complex interactions and shifts during the development of diabetes by simulations. Additionally, an improved evaluation of experimental results will be enabled. The model is adaptable to biological questions in diabetes research.

Beside model analysis, the mathematical focus will lie on methods for parameter estimation by connecting kernel-based methods of learning machines and function approximation with methods for parameter estimation.

Partner:

Obesity, type 2 diabetes and microbiome in mice

Obesity has widely been discussed as a risk factor associated with type 2 diabetes. In addition, it has been reported that obesity is associated with the composition of the gut microbiome. We use mouse models to analyse the association of diet, obesity, diabetes and the microbiome. High-throughput sequencing data is processed from raw data and statistical methods are applied to integrate large scale gut microbiome data with host metabolomics data. We aim to understand the interaction between the host metabolome and the microbiome and their relationship to obesity and type 2 diabetes.

Source: HMGU

Partner:

Understanding of the gut microbiome in children at increased risk of type 1 diabetes

Type 1 diabetes is an autoimmune disease with worldwide increasing incidence. Being a systemic pathological state, autoimmunity is influence by genetic and environmental factors, most of the latter are still widely unknown. Recent work on murine models supports the hypothesis that within onset and development of the disease, the bacterial community in the human intestinal tract is an important actor. Embedded within an international consortium under leadership of the Juvenile Diabetes Research Foundation (JDRF), Helmholtz Zentrum München and The Broad Institute of Harvard and MIT have started a cooperation with the aim to unravel the role of the human gut microbiome in children at increased risk of type 1 diabetes. The Helmholtz International Research Group aims at strengthening this cooperation among internationally leading institutions in diabetes research through both, education of young scientists in interdisciplinary, systemic approaches for diabetes research, and lifting the project oriented cooperation onto an ongoing, long lasting basis.

Partners:

Funding:

Helmholtz Association
(Helmholtz International Research Group)