Antibody structure, antibody engineering, mucosal immunology, retroviral envelopes, electron paramagnetic resonance, electron microscopy, X-ray crystallography

Host-microbe coevolution has produced intricate interspecies relationships in which countless host and microbial proteins interact, ultimately influencing the fitness of both species. Yet, the molecular mechanisms that define many host-microbe interactions remain unexplored, limiting our ability to understand and influence health and disease. To address this challenge, the Stadmueller Lab studies proteins and protein complexes found in the immune system, bacteria and retroviruses using an approach that combines structural biology and biophysics, (e.g. X-ray crystallography, electron microscopy and electron paramagnetic resonance spectroscopy) with protein engineering and animal models of disease.

The lab focuses on two specific biological topics: (1) We investigate the unknown structures and mechanisms of the predominant mucosal antibody, secretory IgA (SIgA), in order to determine how its poorly understood, polymeric architecture can support both pathogen clearance and commensal microbe homeostasis and how we can engineer antibody-based therapeutics to modulate these two functions. (2) We investigate endogenous retroviral envelope (env) proteins, fusogenic proviral proteins expressed from ancient retroviral DNA elements that have integrated into host genomes over millions of years, in order to determine how retroviral env structures and mechanisms have been co-opted through host evolution to support endogenous functions (e.g. embryo implantation) and how they contribute to disease states such as cancer and HIV infection. The broad, long-term goal of these two projects is to understand how protein structure and function has shaped the relationships between the vertebrate immune system, bacteria and viruses and using that information, to develop protein-based therapeutics that can modulate host-microbe interactions.