Model Systems for Infection and Immunity
In infection research experiments on cells and mice have a pivotal role. Frequently such model systems have to be tailored to allow tackling a specific scientific question. To this end, genetic modification of cell lines and mice is being pursued.
To design reliable model systems, genetic modifications should be predictable, reliable, and, most importantly, effective. While the standard procedures cannot meet these requirements our scientists have developed highly effective protocols to guarantee that genetic modifications will have the desired effect in cells and/or transgenic mice. As such, genetic elements to control gene functions – called expression cassettes – are not randomly integrated into the cell’s chromosomes but targeted to preselected chromosomal loci. This allows rule out the negative impact of regulatory elements that are frequently associated to randomly chosen chromosomal sites. Moreover, this allows to ensure tight regulation of synthetic expression cassettes that can be externally controlled and switched on or off on demand.
For their experiments, HZI researchers are using immortalised cell lines that can be expanded to unlimited numbers and thus provide an important source of material. In many cases, however, these cell lines have lost their original properties and thus no longer mirror the respective cells in the body. Accordingly, they are suited to only a limited number of questions.
To get around this dilemma, our scientists have developed a strategy to immortalise cells in a way that allows to tightly regulate proliferation and to put a time limit on cell growth. To this end, the researchers introduce genetic elements into the cells that control the cell cycle and can be switched on or off using externally added small molecules. By this procedure, the cells can be expanded on demand but still retain their original properties. Thus, they represent valuable model systems for infection research.
The next step leads from a cellular system to an animal model. Our scientists are developing mouse models that allow studying the complex response during infection with all its contributing cell populations. One research focus is chronic hepatitis, which is frequently associated to hepatitis B or hepatitis C viral infection. Because normally only humans and apes are susceptible to these viruses, HZI researchers developed transgenic mice in which viral genes are specifically switched on in the liver. These mice develop a pronounced hepatitis which is currently used to studying the chronic course of the disease.