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. 

Leader

Our Research

The research group MSYS develops model systems to elucidate specific questions in chronic virus infection. To this end, tools of synthetic biology are employed. The developments comprise cell based systems (2D and complex 3D systems including organoids) which are analysed both in vitro and also after transplantation into mice. Further, transgenic mouse models are developed to spatially and temporally control transgene expression.

1. Immune response in tolerogenic organs

Acute infections with hepatotropic viruses such as HBV and HCV are often successfully controlled by the human immune system and are frequently not noticed. Still, in many patients this immune response fails or is not efficient enough. Thus, viruses are not eliminated and chronic infection states are established. The reason for this impaired immune response is not understood. Researchers of the MSYS group investigate the immune response in tolerogenic organs such as liver and lung. To this end, they use previously developed transgenic mouse models in which (viral) antigens are exclusively induced in the respective tissues. The long term goal is the development of strategies that facilitate powerful immune responses in these organs and may contribute to the therapy of chronic viral infections.

2. Novel (cell based) models for Herpes virus infections

The investigation of many infections requires human cells. However, the availability and quality of human cells is restricted. The research group MSYS develops strategies to expand human cells without loosing their cell type specific properties. One recent example for such a development is the human endothelial cell line huARLT. This cell line not only represents all relevant properties of endothelial cells but also provides the option to control cell growth. Moreover, upon transplantation into immune compromised mice, functional vessels are formed that are connected to the mouse vasculature. Based on these cells we investigate the infection with chronic herpesviruses (KSHV, CMV) both in vitro (2D and 3D culture systems) as well as in the mouse. Finally the systems are refined to validate novel antiviral compounds. 

3. Controlled (epi)genetic modifications

Cell and mouse systems with novel or altered properties (such as exemplified above) can only be generated by controlled modification. To this end, we employ genetic engineering as well as epigenetic editing. An important method is the introduction of synthetic expression modules into the host’s genome. However, upon chromosomal integration the synthetic cassettes interact with the regulatory elements of the host cell and the level but also the stability of transgene expression crucially depends on the properties of the particular chromosomal integration site. Researchers of MSYS thus aim at integrating the synthetic cassettes in a way that the final expression properties are highly predictable. This includes strategies to overcome epigenetic silencing. 

The tools of synthetic biology are also employed to create cells that sense physiological signals and rewire them to therapeutic outputs. One of the current projects aims at developing cells that sense and combat inflammation.

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