Bork Group
Deciphering function and evolution of biological systems
Integration of various -omics data from a genomereduced bacterium, Mycoplasma pneumonia. Together with other SCB groups, we overlay genomic, transcriptomic, proteomic, metabolic and structural data to establish a model organism for systems biology and discover lots of exciting biology on the way (see Kuehner et al., 2009, Guell et al., 2009 and Yus et al., 2009, all Science). The figure depicts a tomographic snapshot, a single particle EM of the ribosome (many proteins of which have unexpected links to various cellular processes indicated by lconnectors) and a metabolic reconstruction in which the correspondence to operon organisation is shown (blue)
By analysing and comparing complex molecular data, the Bork group predicts function, gains insights into evolution, and makes connections between genes, organisms and ecosystems.
Previous and current research
The group currently works on three different spatial scales, but with common underlying methodological frameworks:
- genes, proteins and small molecules;
- networks and cellular processes;
- phenotypes and environments, often related to diseases.
We are aiming at biological discoveries and often develop tools and resources to make this happen. We usually work in new or emerging areas; for example we have projects that integrate drugs (and other small molecules) with cellular and phenotypic information to predict new uses for old drugs (e.g. Campillos et al., 2008, Science) or find biomolecules that cause disease or side effects. We study temporal and spatial aspects of protein networks to identify biological principles that determine function and evolution (e.g. de Lichtenberg et al., 2005, Science; Jensen et al., 2006, Nature; Kuehner et al., 2009, Nature). We also trace the evolution of the animal gene repertoire (e.g. Ciccarelli et al., 2006, Science) and, for example, connect gene losses and duplications with morphological or lifestyle changes. We study environmental aspects via comparative metagenomics (Tringe et al., 2005, Science; von Mering et al., 2007, Science; Qin et al., 2010, Nature) and hope to find marker genes for various diseases like obesity and cancer. We also aim to understand microbial community interactions, with application potential for human health and well-being. For example, our recent discovery of enterotypes – three distinct community compositions in the human gut analogous to blood groups (Arumugam et al., 2011, Nature) – was considered as one of the breakthroughs of 2011 by Science because it might explain different responses of people to drug intake and diet. All our projects are geared towards the bridging of genotype and phenotype through a better understanding of molecular and cellular processes.
Integration of metagenomics data with environmental factors. Using novel visualization concepts and statistical approaches we can correlate the abundance of molecular functions to external data (e.g. Gianoulis et al., 2009, PNAS; Qin et al., 2010, Nature). For example, many distant ocean samples are analysed and the abundance of some pathways significantly correlate with temperature or oxygen concentration of both. In human, we find correlations of gut genes from metagenomes with several diseases.
Future projects and goals
Much of the group’s focus in the coming years will be on the human gut. We aim to understand biological processes upon drug treatment, considering ‘human’ as a biological system with various readouts, from drug side-effects to toxicology data. We will explore networks between proteins and chemicals such as lipids or carbohydrates and link them to phenotypic data such as disease status. We will also look at the 2kg or so of bacteria in our intestinal system, study them as communities and explore their impact on colorectal cancer and various other diseases in the context of lifestyle and other parameters. Potential applications could include microbial biomarkers for diseases or antibiotic resistance potential. We also want to understand how microbial communities evolve in us, how frequently they are transmitted parentally or horizontally, and how they communicate with each other and with our cells. Other projects include involvement in collaborations studying various other systems, such as biodiversity (with the TARA Oceans project).
The group is partially associated with the Max Delbrück Center for Molecular Medicine in Berlin and with the Molecular Medicine Partnership Unit.
