Omics and gnotobiosis – tackling host-microbial complexity from two ends

The interactions between the many different colonizing bacteria and their host are manifold and result in a very complex interaction network. The term “Systems Biology” has been coined for the attempt to analyze complex biological systems in their entirety and all their complexity, using the co-called “-Omics” approaches. Advanced computational methods need to be employed to make sense of the resulting highly complex data sets. But uncovering the underlying biological mechanisms from such data has been challenging.

Complementary “Minimalist” approaches, which experimentally reduce complexity as far as possible, can help to reveal the contribution of discrete biological components. One technology we extensively use for this purpose is gnotobiosis (translated: “known life”). Gnotobiotic animals are colonized with a defined selection of microbial species; in our laboratory their number ranges between zero (“germ-free”) and 13 bacterial species.

“Self-Destructing” bacteria to achieve “Reversible Colonization”

Genetically engineered, “artificial” organisms can be powerful tools for uncovering the “essence” of their effects on our body.

“This bacterium will self-destruct in … one generation…”

One of our favorite tools are “self-destructive” bacteria that depend on supplementation of the peptidoglycan peptide amino acids D-alanine and meso-diaminopimelic acid in the growth medium. These are exclusively microbial metabolites that cannot be provided by the host organism. Our first version of a self-destruct bacterium, strain “HA107”, was based on E. coli K-12. In the first publication (Hapfelmeier et al. 2010, Science 328(5986):1705) we used the ability to fully reversibly colonize germ-free animals with it to study the dynamics and stability of commensal bacteria-induced intestinal IgA antibody.

Synthetic Biology: Remote controlled bacterial “drones”

We are working on new ways to remotely control the behavior of bacteria inside the host.

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Studying the microbiota-host interplay directly by live microscopy

Dr. Fernanda Coelho-Matos, an up-and-coming young expert for 2-photon microscopy, has joined the team to study the microbiota-host microcosm directly and dynamically by live-microscopy. The intestinal-microbial ecosystem is clearly much more than a flexible tube that pumps dietary content and microbes. We believe it has an ordered, albeit dynamic, structure that is difficult to capture ex vivo.

You would not try to study the jungle by throwing it in a gigantic blender to extract its DNA and metabolites. You must also go there. Fernanda will embark on a groundbreaking intestinal fieldwork trip, through the 2-photon-micrscope in the laboratory. A lot of uncharted territory!

Regulation of Clostridium difficile in the intestine: when, where, how?

In progress.

3rd-Generation Real-Time DNA Sequencing – Hapfelmeier lab joined the Minion® MAP program

We are proud and excited to be now part of the “MinION Access Program” (MAP) recently launched by Oxford Nanopores. We thus joined a community of beta-testers at the forefront of next-generation sequencing. More information soon! Follow us on twitter.

The curious microbial biology of D-alanine

More information will be added soon. Follow us on twitter.

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