Humboldt-Universität zu Berlin

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Overview

Research Groups:

P. Hammerstein
A. V. M. Herz
H. Herzel
R. Kempter
M. Or-Guil
L. Wiskott

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Research Group "Systems Immunology"

Dr. Michal Or-Guil

 

There are open PhD or postdoc positions in the group! (Details here)

 

In order to identify a foreign organism, the mammal immune system exploits the protein binding activity of antibodies. In dependence on the invader, highly specialized antibodies are secreted by suitable cells which are selected out of a large cell pool and induced to expand their population. The group's research aims at answering questions like: What are the mechanisms governing the selection of the most suitable cells, and how are the selected cells improved during the course of an acute immune response? What recognition properties must a set of antibodies possess to be able to locate any invading pathogen? We pursue an interdisciplinary approach combining mathematical modeling, data analysis and experimental work. 

The Junior Research Group is funded by the VolkswagenStiftung. Its research is divided into three subprojects:
 

B Cell Selection and Antibody Evolution in Germinal Centers

The spatial and temporal regulation of the selection of antibody producing cells (B cells) in germinal centers is investigated both in vivo by inspecting tissue sections, and by  means of mathematical models and computer simulations. The understanding of the selection mechanism is of paramount importance to comprehend the evolution of binding affinities of antibodies during an immune response. Experiments are conducted in close cooperation with the DRFZ in Berlin.

Statistical Analysis of Protein Binding Data

Cross-reactivity and affinity of antibodies are investigated by screening their binding properties against large numbers of peptides. Data analysis of serum binding patterns reveal a better understanding of what accounts for the differences and conditions of varying immune systems. The highly advanced  technology we use is also applied for the development  of a concept of "shape  space", based on experimental data. In cooperation with Jorge Carneiro at the Gulbenkian Institute in Portugal and Jerini AG and the Molecular Libraries and Recognition Group at the Charit� in Berlin.

 

Dynamics of Protein Degradation by Proteasomes

Proteasomes are large molecules which are present in all cells of the body. They have the task of degrading proteins which are not being used by the cell, and they accomplish this task by cleaving these superfluous proteins into small fragments. The fragments are cut in such a way that some of them possess the right size to be presented to the immune system on the cell surface. It then lies upon specialized immune system cells to decide if the presented fragments stem from harmless self-proteins, or if there are pieces of pathogens among them. In the latter case, the cell will be told to destroy itself, and with that it will also destroy the pathogens it is unwillingly hosting.

The group investigates protein cleavage by proteasomes by mathematical modeling, intending to specify which are the dynamical features of the cleavage mechanism that lead to the production of fragments possessing the right size to be presented to the immune system, and how this mechanism changes for different proteasomes.

 

Group Members

Dr.Michal Or-Guil

Nicole Wittenbrink

Fabio Luciani

Nicole Bruni

Victor Tapia