29. Hermann Staudinger Lecture: "Discovering TNF, TLRs, and other Key Components of the Immune System"

Early in his early career, Nobel Laureate in Medicine or Physiology 2011 Bruce Beutler isolated mouse TNF, a protein secreted by macrophages in response to lipopolysaccharide (LPS). He determined that TNF mediated many LPS effects, including systemic inflammation, shock and death. His attention was drawn to the LPS receptor, which was responsible for alerting mammals to the presence of Gram(-) infection. His colleagues and him identified it as Toll-like receptor 4 by positional cloning and revealed an entire family of innate immune receptors that recognize molecular signatures of infection. This experience led them to create many other immunological phenotypes through random germline mutagenesis. They tracked them down one by one. In recent years, his laboratory has developed automated meiotic mapping (AMM), which makes positional cloning an instantaneous procedure. Using AMM, they have positionally ascribed approximately 30,000 phenotypes to individual mutations: an accomplishment that only recently would have required thousands of years. This has allowed them to identify the majority of genes needed for robust immunity and also has opened the door to a systematic search for disease modifier mutations.

The lecture was given as part of the Staudinger Lecture Series at the Freiburg Institute for Advanced Studies on October 4th, 2022 (Germany).