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uni'wissen 02(4)-2011_ENG

show that some pathogens and pathogen prod- ucts, such as certain poisonous substances, can play an active role from outside of the cell,” ex- plains the signaling researcher. Previously, pro- cesses like that in which the cavities are formed were believed to be caused by the cell’s own pro- teins alone. “Hardly any research has been con- ducted on how these proteins admit poisonous substances into the cell independently.” Mem- brane lipids play a decisive role in this process. They are responsible for keeping the cell mem- brane stable, flexible, and partially permeable. When the bacterium binds to this membrane, sig- naling processes are triggered, which in turn at- tracts structural proteins that make the growing tubes with the bacteria split up into tiny bubbles inside the cell. The pathogen has now finally reached the inside of the cell. As a postdoc at the Curie Institute, Winfried Römer conducted his first experiments in this area not with bacteria but with poisonous sub- stances, so-called toxins. “The transitions from toxin to virus and from virus to bacteria constitute enormous increases in complexity and magni- tude for research,” says the researcher. “It is im- portant to start with simple systems before tack- ling the more complex ones.” Using viruses introduced as pathogens, Römer and his col- leagues were able to demonstrate that the path described above is the main path of infection and that it depends on special lipids. The goal of all of his experiments is to learn more about endocyto- sis, the absorption of molecules into the cell, and the immense cellular machinery this process sets in motion. The scientist is convinced that patho- gens from outside are not the only bacteria that make use of the cellular apparatus. In a few years, when he has unraveled the individual steps of endocytosis and their various microbial and cellular factors, he hopes to also be able to identify molecules from the body that use this path to enter cells. “At the moment we are using the pathogens as a means to an end, as hijack- ers that take control over the machinery of the host and manipulate it to make an infected cell out of a healthy cell,” says Römer. His research is facilitated by the fact that most pathogens are specialized in using lectins to attach themselves to cell membranes with sugar. Experiments have shown that the pathogen does not bind with the host cell when modified bacteria without lectins are used. “There is more and more evidence that bacterial lectins are absolutely necessary for a successful invasion of the cell.” The Human Cell Is a Good Hiding Place The experiments on the first steps of the cell invasion are already underway, as are those on the behavior of the pathogen once it has entered into the cell. It adapts to the micro-environment inside of its bubble and “avoids fusing with the compartments of the cell like the plague.” Par- ticularly dangerous for the pathogen are lyso- somes, organelles that eliminate waste by de- stroying everything that doesn’t belong in the cell. “Our hypothesis is that the pathogen uses Further Reading Römer, W./Pontani, L./Sorre, B./Rentero, C./ Berland, L./Chambon, V./Lamaze, C./ Bassereau, P./Sykes, C./Gaus, K./Johannes, L. (2010): Actin dynamics drive membrane re- organization and scission in clathrin-indepen- dent endocytosis. In: Cell 140/4, p. 540 – 553. Römer, W./Berland, L./Chambon, V./Gaus, K./ Windschiegl, B./Tenza, D./Aly, M. R./Fraisier, V./ Florent, J.-C./Perrais, D./Lamaze, C./Raposo, G./Steinem, C./Sens, P./Bassereau, P./Jo- hannes, L. (2007): Shiga toxin induces tubular membrane invaginations for its uptake into cells. In: Nature 450, p. 670 – 675. “The transitions from toxin to virus and from virus to bacteria constitute enormous increases in complexity and magnitude for research” 14 uni'wissen 04