Dresden International Graduate School for Biomedicine and Bioengineering

Our laboratory is focused on understanding how lipids contribute to membrane function and organismal fitness from synthetic protocells to microorganisms. We are interested in topics ranging from how membranes contributed to the origin of cellular life, to identifying membrane-based targets for antibiotic resistance. One of our central aims is to mine a repertoire of biological innovations from the simplest microorganisms to elucidate the minimal set of principles and components required to assemble a robust and autonomous synthetic cell membrane.

Cells are complex interconnected systems with many processes occurring in parallel The complexity and robustness of the cell is crucially dependent on the ability to orchestrate localization of a staggering number of simultaneously occurring biochemical processes. Lipid membranes play a central role in this partitioning of bioactivity. Membranes serve a dual role as a selectively permeable barrier, and as a two-dimensional solvent hosting biochemical activity (e.g. signaling, transport, growth and division). The ability of membranes to perform these crucial roles rests on the collective interactions of lipids and proteins, and the physical and chemical membrane properties resulting from these interactions. Our lab broadly aims to understand how lipids modulate cell membrane function and to apply this knowledge to engineer synthetic biological systems from the bottom up.

I did my postdoctoral work at the MPI-CBG with Kai Simons investigating what preceded sterols in the evolution of membrane organization and elucidating the molecular basis for such organization in bacterial membranes. I demonstrated that hopanoids, ancient bacterial lipids, are biophysically similar to sterols in their ability to order membrane lipids and to form liquid ordered domains (Saenz et al., 2012). This observation alters our understanding of membrane evolution, suggesting that the emergence of ordered biochemically active liquid membranes, and thus the ability to subcompartmentalize membranes, preceded the evolution of sterols. This not only suggests that liquid-ordered membranes may be common outside the Domain Eukarya, but it decouples the evolution of this trait from the requirement for molecular oxygen. Following on these discoveries, I began work to understand the biological role of sterol analogues in bacterial membranes. I discovered that hopanoids interact with glycolipids in bacterial outer membranes to form a highly ordered bilayer in a manner analogous to the interaction of sterols with sphingolipids in eukaryotic plasma membranes (Saenz et al., 2015). This revealed a convergence in the architecture of bacterial and eukaryotic membranes and implicated the biosynthetic pathways of hopanoids and other order-modulating lipids as potential targets to fight pathogenic multidrug resistance.