The research group Dagan aims to understand lateral processes in microbial evolution. We use experimental and genomic methods to study evolution in bacteria and the contribution of particular gene transfer vectors to adaptation. Within EvoLUNG, we are studying the evolutionary mechanisms of Mycobacterium tuberculosis. Its consideration as a purely clonal lineage is challenging our understanding of the mechanisms of bacterial adaptation. Densely sampled genomic data are available and will be used for a reevaluation of the contribution of horizontal processes to Mycobacterium tuberculosis evolution.
Evolutionary Ecology and Genetics
The research group Schulenburg is interested in understanding the process of evolution, including the underlying ecological and genetic mechanisms. We focus on host-microbe interactions and study host-pathogen co-evolution, bacterial adaptation to antibiotics, the evolution of host immunity, and host-microbiota co-adaptation. Within EvoLUNG, our particular interest is to improve our understanding of antibiotic resistance evolution of pathogenic Pseudomonas aeruginosa, one of the dominating infectious agents of adult cystic fibrosis patients. Our aim is to understand the causes and consequences of rapid evolution of these pathogens and exploit this understanding for the design of novel, sustainable antibiotic therapy.
Molecular and Experimental Mycobacteriology
The research group Niemann aims for a better understanding of host and pathogen related factors impacting on Mycobacterium tuberculosis complex (MTBC) strain infections, tuberculosis disease outcomes and evolution of drug resistance. To target this challenging goal within the EvoLung campus, we combine results from infection models, next generation sequencing (NGS) transcriptome analysis and available genome sequencing data from over 10,000 worldwide circulating clinical MTBC isolates. With this integrative approach, we sought to determine virulence factors, pathogenicity signatures, bacterial fitness enhancing mutations, and evolutionary trajectories that affect long-term and short-term drug resistance development and host-pathogen interactions.
The research group Baines aims to understand the interplay between mammalian hosts and their associated microbial communities from an evolutionary perspective in order to gain novel insight into human health and disease. In the context of EvoLung, we are trying to further establish the importance of the resident lung microbiota by determining the role of host genetics in shaping variation in the lung microbiota. With this approach we aim to identify key host gene-microbe interactions that can be investigated in the context of chronic lung disease.
The Cellular Microbiology group studies host-pathogen interactions in tuberculosis (TB) on the molecular, cellular and animal model level. Our work is based on the question how the intracellular niche of the agent, Mycobacterium tuberculosis, determines the pathogens fate and its transmission as well as innate and acquired immune responses and pathogenesis in tuberculosis and, ultimately, anti-mycobacterial drug efficacy. We recently included the lung micro-ecology as a so far neglected influencing factor of pulmonary host responses against tuberculosis in our studies. Therefore, we provided the first thorough description of the murine lower airway microbiota. These studies provide the basis for the EvoLUNG project on the mutual influences between pulmonary microbiota, host iron metabolism genes and mycobacterial pathogens on experimental tuberculosis in mice. Thus, resistance/susceptibility to TB as a result of host-microbiota-pathogen co-evolution driven by competition for iron will be tested.
Asthma results from a complex interaction between an individual's evolutionary evolved genetic make-up and the environment. Within EvoLUNG the research groups Wagner & Krauss-Etschmann aim at deciphering the functional relevance of serpine (serine-protease inhibitor) gene variants for the pathogenesis of bronchial asthma. In detail we are exploring how the chance of developing asthma is increased, when carriers of these gene variants are exposed to known risk factors for asthma (e.g. cigarette smoke). To clarify this issue, we primarily use the fruit fly Drosophila melanogaster. Due to its short generation time, high fertility, ease of genetic manipulation and presence of homologue genes, Drosophila facilitates studying the fitness effect of gene variants associated with complex human diseases. To elucidate the pathophysiological role of serpine gene variants in asthma development, the analysis will be completed by in vitro as well as in vivo studies in mice.
The major goal of the research group Roeder is to understand molecular processes underlying various human diseases. We use the fruit fly Drosophila melanogaster as a model for various chronic metabolic, intestinal and lung diseases. In EvoLUNG, we use these Drosophila models and apply concepts of evolutionary medicine to understand the molecular framework underlying COPD (Chronic Obstructive Pulmonary Disease). Based on a cigarette smoke model of COPD, the pathophysiological relevance of selected susceptibility genes will be evaluated and used to a) learn more about the molecular mechanisms relevant for disease development and b) identify new treatment strategies to fight this disease.
Early Life Origins of Chronic Lung Disease
Within Evolung, we aim to clarify to what extent the host microbiome shapes asthma susceptibility independent from the host genetic make-up. To this end, we will use the microbiotas of four genetically different mouse strains having distinct asthma susceptibilities to re-colonize genetically identical, germ-free mice. In a second approach, we will perform litter-swap experiments where offspring from "asthma-high" mothers will be raised by "asthma-low" mothers and vice versa. This work will clarify if targeting the microbiome is or is not a promising approach to prevent or treat allergic asthma in the future.