Disease Systems Biology

Advances in medical research revealed that a disease phenotype is the result of pathobiological processes that interact in complex networks. The group works on computational data integration approaches where clinical and phenotypic data are combined with molecular level data, predominantly exome and transcriptome information. One important aim is to identify the genetic contributors to human variation in drug efficacy, which is an important aspect in personalized medicine. By longitudinal exome analyses of the tumor heterogeneity we can significantly reduce the number of hits for functional validation. Another focus is to apply RNA sequencing of human tissues and network biology to study the complexity of the biochemical networks at multiple scales for understanding the development of metabolic diseases, and specifically diseases linked to energy storage.

Systems biology of fungal infection aims at understanding the interaction of the host, in particular the immune system, with components of the fungal pathogens by analysing two interacting networks. Gene regulatory network models were and will be reconstructed (inferred) based on the analysis of high-throughput data integrating prior knowledge. The inference of transcriptional regulatory networks allows for an incorporation of both the gene expression data together with promoter sequence information. As a result, a set of potential target genes can be predicted, which are presumably responsible for the interaction of the fungal pathogens with the host. This information, in turn, can be used as a starting point for the investigation of the host’s response to the pathogen’s attack.

Diet

It is well known that nutrition is the cornerstone of an individual’s environment, as such understanding how diet influences metabolic regulation and how dietary interventions can improve health is a key scientific goal. Furthermore, diet has a major influence on the overall quality of life beyond the prevention of diseases and its role is fundamental for individual performance and enjoyment. Even though the personalized approach to diet is the logical next step – much like the transition from pharmacology to personalized medicine – this task is extraordinarily complicated. Most foods are composed of hundreds of bioactive compounds, often interacting with each other. Furthermore, the targets are of varied concentrations and different targets have different affinities and specificities. Unfortunately, nutritional trials are not designed for mechanism-based preclinical studies, and little is known about their molecular targets. Our group integrates text mining, chemoinformatics and network biology for performing global analyses of diet that elucidates the synergistic interactions of small molecules that yield specific phenotypes and hopefully contribute towards personalized nutrition.