Bridging Excellence Lectures

"Disease-specific gut microbial signatures for colorectal cancer identified in metagenomic meta-analysis”

Using fecal metagenomes we explored the potential of microbiome signatures for non-invasive colorectal cancer (CRC) detection. The accuracy of these signatures is on par with a widely used non-invasive clinical screening tests (the FOBT) and can be further improved by combining both tests. In a meta-analysis of eight CRC microbiome studies we have established global predictivity of microbial CRC signatures and demonstrated their disease specificity. An analysis of microbial genes and pathways confirmed the global prevalence of several known mechanism by which gut bacteria can contribute to cancer progression. Additionally we found a highly significant and predictive enrichment of secondary bile acid metabolism genes in CRC metagenomes suggesting this to be an important carcinogenesis process that may be linked to established dietary risk factors for CRC.

Bio

Georg Zeller is a group leader at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. His group develops analysis strategies and computational tools to extract robust microbiome disease signatures from functional and taxonomic metagenomic profiles in cross-study comparisons. He is further interested in mining metagenomes for candidate genes and pathways by which gut microbiota might contribute to initiation and progression of gastrointestinal diseases such as colorectal cancer.

Georg Zeller studied Computional Biology at the University of Tuebingen, Germany, and Uppsala University in Sweden. For his PhD, he worked with Gunnar Raetsch and Detlef Weigel at the Max Planck Institutes in Tuebingen and subsequently joined Peer Bork's group at EMBL for a postdoc.

"Developments in 3D Super-Resolution Microscopy and Single-Particle Tracking in Cells with Single Molecules”

Super-resolution microscopy has opened up a new frontier in which biological structures and behavior can be observed in fixed and live cells with resolutions down to 20-40 nm and below.  Examples range from protein superstructures in bacteria to bands in axons to details of the shapes of amyloid fibrils, cell surface sugars, protein superstructures in the primary cilium, and much more.  Current methods development research addresses ways to use ideas from machine learning and convolutional neural nets to enhance image processing. For super-resolution imaging in thick cells, a new tilted light sheet design makes use of PSF engineering to create a simple, useful microscope. Low temperature single-molecule imaging provides much improved localization precision in order to complement cryo-electron tomography studies. Still, it is worth noting that in spite of all the interest in super-resolution microscopy of extended structures, even in the “conventional” single-molecule tracking regime where the motions of individual biomolecules are recorded in cellular environments, much can be learned. Combining super-resolution imaging of a static structure with 3D tracking of other biomolecules provides a powerful view of cellular dynamics.

Bio

William E. Moerner is a Harry S. Mosher Professor of Chemistry, as well as a Courtesy Professor of Applied Physics at Stanford University. With a multifaceted background in physics, math, and engineering, Prof. Moerner has driven the development of super-resolution optics and imaging for cell biology in 2D and 3D. He has been recognized for his influential contributions to the field with a number of prestigious awards, most notably a Nobel Prize for Chemistry in 2014. A leader in super-resolution imaging, the Moerner Lab develops and employs methods combining laser spectroscopy and microscopy of single molecules in order to probe biological processes at the smallest scale.