Max-Planck scientists aid research that leads to Nobel Prize
- Date:
26.10.2011
The Freudenberg Lab at the MPI of Immunobiology and Epigenetics with Marina Freudenberg (middle) and Chris Galanos (3rd from the right)
The 2011 Nobel Prise was awarded to Bruce A. Beutler and Jules A. Hoffmann for discovering receptor proteins that can recognize pathogenic microorganisms and activiate innate immunity.
Bruce Beutler’s aim was to find the signaling receptor for bacterial lipopolysaccharide (LPS). LPS causes activation of the innate immune system and may lead to septic shock, a life threatening condition. In 1998, Bruce Beutler and his colleagues experienced the final break-through: They discovered that mice resistant to LPS carried a mutation in Toll-like receptor 4 (Tlr4), a gene designated earlier as Lps. This gene is similar to the Toll gene of the fruit fly Drosophila Melanogaster. The binding of LPS by TLR4 leads to an activation of signals that cause inflammation and in the worst case septic shock. Bruce Beutler’s findings showed that mammals use similar molecules as fruit flies to activate innate immunity when encountering microorganisms that invade human and animal body.
The key publication that led to the awarding of the Nobel Prize was co-authored by the Max-Planck scientists Marina Freudenberg and her husband Chris Galanos. These two researchers studied for many years biological responses to LPS and at the beginning of ninteen ninties became interested in the identity of the LPS receptor. They invited Bruce Beutler as speaker at the Annual Conference of the Upper Rhine Universities and for discussions about possible strategies to identify the LPS receptor. In the Journal of Endotoxin Research 2000 (Review: The search for Lps: 1993 – 1998), Bruce Beutler acknowledges the contribution of Chris Galanos and Marina Freudenberg to the discovery of TLR4 as LPS receptor. Here the exert from the above publication:
„ I held ..innumerable conversations about Lps with Chris Galanos and Marina Freudenberg, who were immensely curious about the nature of this gene: in particular, about the nature of the difference between mutations in the C3H/HeJ and C57BL/10ScCr strains of mice....In 1990, Chris and Marina were the first to impress me with the importance of these animals. Then and later, we spoke for many hours about the two strains of mice: specifically, about the relative resistance of the two strains to LPS, and about the different effect of infectious agents in modulating resistance to LPS a phenomenon which escapes complete understanding even today*. They would, in coming years, examine the possibility that CD14 expression might be aberrant in C3H/HeJ mice, and would find that it clearly was not. Their insight into the system of LPS response was always valuable to us and, during the years that followed, they provided us with macrophage RNA and genomic DNA from the C57BL/10ScCr mice: materials that we used frequently in attempting to exclude or confirm candidate genes!“
* In the mean time this has been elucidated (Merlin T. et al. J. Immunol. 2001, 166: 566 and Poltorak A. J. Immunol. 2001, 167: 2106)
