Philipp Lachenmann: DELPHI Rationale


Avrion Mitchison Prize 2010

Dr. Edda Schulz

Institut Curie, Paris 

"Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-g and interleukin-12"

Dr. Edda Schulz studied Biochemistry at Eberhard-Karls-University, Tübingen. From 2005 to 2009, she completed her dissertation on „experimental and mathematical analysis of regulatory networks in T-helpertype I (Th1) lymphocytes” under the supervision of Prof. Thomas Höfer, Humboldt-University, Berlin, and Prof. Andreas Radbruch, German Rheumatism Research Center, Berlin. In 2008, she worked as a post-graduate researcher at Harvard Medical School, Boston, USA. Since 2010, she has been a postdoc in the research group „Mammalian Developmental Epigenetics” at Institut Curie, Paris, France.

Dr. Edda Schulz will receive the Avrion Mitchison Prize 2010 of the German Rheumatism Research Center in Berlin. At the award ceremony on November 30, she will give a talk on “Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-g and interleukin-12“.

Schulz about her research:
T-helpertype I (Th1) lymphocytes play a central role in the mammalian adaptive immune response against intracellular pathogens. When activated inappropriately, however, they contribute to autoimmune diseases. Although transcription factors and cytokine signals controlling Th1 differentiation have been studied extensively, the exact contribution of each factor remained unclear. It had been known for long that the Th1 master transcription factor T-bet can be induced by the cytokine interferon-g (IFN-g) in an autocrine manner. However, it had remained puzzling, why IFN-g cannot induce Th1 differentiation, which requires another cytokine, interleukin-12 (IL-12). To understand how the various players function together as a regulatory network, a systems biology approach was chosen.

Through close interplay of quantitative experiments and mathematical modelling, the gene-regulatory network governing differentiation of Th1 cells was reconstructed. The Th1 network was found to successively adopt two different states, each controlling a distinct phase of the differentiation process. During an early effect or phase cells fulfill Th1 functions but remain uncommitted, while the following differentiation phase is required for lineage stabilization. The antigenic signal acts as a switch between the two network states since it is required for effect or functions (IFN-g production), but inhibits response to the differentiation signal IL-12. The Th1 master transcription factor T-bet can mediate lineage commitment only during the late differentiation phase. It could be shown that IL-12 drives T-bet differentiation during this differentiation time window, which explains the unique role of IL-12 in Th1 differentiation. Therefore, this network analysis of the dynamic interactions between known key regulators solved a long-standing question regarding the different roles of IFN-g and IL-12 during the Th1 differentiation process.

Award Ceremony and Lecture on November 30, 2010, at 5 p.m.

The Avrion Mitchison Prize, which is funded by the Ernst Schering Foundation, is presented in conjunction with the Albrecht Hasinger Lecture at the German Rheumatism Research Center (DRFZ).

Foyer of the German Rheumatism Research Center Berlin
Charité Mitte Campus
Charitéplatz 1
10117 Berlin





Edda Schulz


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