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Hermann Staudinger Lecture – Discovering TNF, TLRs, and other key components of the immune system

The Hermann Staudinger Lectures are a series of talks initiated by the School of Soft Matter Research in 2008. FRIAS invites international Nobel laureates to give a lecture in Freiburg two to three times a year. The lecture series is named after Nobel Laureate Hermann Staudinger who taught at the University of Freiburg from 1926–1951 and was awarded the Nobel Prize in Chemistry in 1953.

Discovering TNF, TLRs, and other key components of the immune system

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


Interne Verantwortlichkeit:
FRIAS Mathematik, Naturwissenschaften

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