Deciphering function and evolution of biological systems
Multiple roles for different microbial communities in the human gut (modified from the German newspaper Zeit covering the work of the group, original designed by J. Schievink). Metagenomic data from thousands of individuals from all over the world are analysed. For example, three stratifying gut microbial community types (enterotypes) have been discovered in the human population (Arumugam et al., 2011); shown are 1000 individuals clustered by their gut microbial composition. Each individual is a dot, coloured by enterotype.
The main focus of the Bork group is to gain insights into the functioning of biological systems and their evolution by comparative analysis and integration of complex molecular data.
Previous and current research
The group currently works on three different spatial scales, but with common underlying methodological frameworks:
- genes, proteins and small molecules;
- molecular and cellular networks;
- microbial communities.
All of these biological entities we try to analyse in the context of their respective environments. We often develop tools and resources – our research is usually in new or emerging areas. Past highlights include work on the Human Genome Project (Lander et al, 2001); as well as being amongst the first to study protein interaction networks (von Mering et al, 2002), microbial communities using metagenomics (Tringe et al, 2005), and drug-target interactions using global readouts such as side effects (Campillos et al, 2007). Other exploratory projects have targeted, for instance, genome evolution, dynamic aspects of networks, post-translational modifications, and data integration for species of interest.
Our current focus is the human gut where, on one hand we employ metagenomics to uncover principles of microbial communities in the human population and in the context of disease, and on the other we use systems pharmacology to understand and predict the impact of drugs on humans at the molecular level. We develop analytic frameworks (e.g. see Qin et al., 2010; Sunagawa et al., 2013) and study stratification of the human population – we found three principle community compositions in developed countries across the world, dubbed enterotypes (Arumugam et al., 2011). We also explore variation at the nucleotide level, where each human appears to carry individual strains (Schloissnig et al., 2013). In the context of such global observations, we hope to find microbial markers for a number of diseases such as obesity (Le Chatelier et al, 2013) and colon cancer.
Furthermore, the human gut does not only harbour hundreds of microbial species, but its environment also impacts the efficacy of orally administered drugs. We try to repurpose existing drugs and to understand more about human biology using large-scale integration of various molecular and phenotypic datasets (e.g. Kuhn et al., 2013, Iskar et al., 2013).
Future projects and goals
We aim to develop community-wide population genetics to understand how microbial communities are transmitted or evolve within ourselves and under which constraints. This might help us to answer many long-standing questions, for instance how many pathogens do we tolerate in us as phenotypically healthy individuals? How is antibiotic resistance developing? For which diseases or phenotypes can we identify microbial biomarkers or can we develop a formula that will replace faecal transplantations? In the future we hope to connect microbiomics with diet, host interactions and drug intake. In this regard, we will continue to explore networks between proteins and chemicals such as lipids or carbohydrates and link them to phenotypic data such as disease status, side effects or toxicology. Several current exploratory projects study, for example, systematically the interactions between post-translational modifications and their evolution.
While the human microbiome will remain our main focus, we will also take part in collaborations exploring other habitats such as the ocean to better understand biodiversity – for example we are involved in the TARA Oceans project (Karsenti et al., 2011). To foster translational research, the group is partially associated with the Max Delbrück Center for Molecular Medicine in Berlin and with the Molecular Medicine Partnership Unit at the University of Heidelberg.