Model Systems for Infection and Immunity

Our Research

The MSYS research group develops model systems to study the host response to viral infections and to develop new counterstrategies against infections. This involves the (epi)genetic manipulation of cells and mice using tools from synthetic biology. Developments include cell-based systems (2D and complex 3D systems including organoids) analysed both in vitro and after transplantation into mice. In addition, transgenic mouse models are being developed to spatially and temporally control transgene expression.

1. Rewiring host response pathways to counteract infections

The innate immune response serves as an early defence mechanism activated by a wide range of pathogens. We engineer synthetic regulatory pathways by integrating the cellular cascade of the innate immune response with synthetic regulatory modules. This approach allows us to effectively rewire cellular signalling cascades to render infections visible and achieve therapeutic outcomes in a precisely controlled, on-demand fashion. Furthermore, harnessing the toolbox of synthetic biology allows modulating therapeutic responses, e.g. to amplify and/or sustain, thereby enhancing the overall outcome. Through this strategy, we create theranostic cells that are able to recognise infection-specific signals and respond with efficient therapeutic actions that counteract infection and/or infection-related pathological responses.

2. Cell-mediated delivery and controlled release of drugs

The use of drugs is often limited by toxic side effects in organs outside the target area, which are caused by the systemic administration of drugs. We are developing strategies to target drug-associated nano- and microparticles to sites of infection. To this end, we exploit the innate properties of macrophages to take up particles and migrate naturally to sites of infection. We use external signals such as therapeutic diagnostic ultrasound or alternating magnetic fields for spatially controlled, on-demand release of drugs from particle-loaded cells at these sites.

3. Investigating host’s response to human restricted viruses

Studying human-restricted infections requires the use of human cells, yet the availability and quality of these cells are often limited. The MSYS research group develops strategies to expand human cells while maintaining their cell-type-specific properties. By integrating these cells into 2D/3D (co-)culture systems, we can uncover the host’s responses and the infection-related consequences on cellular functions within predictive model systems. Current research is focused on SARS-CoV-2, as well as herpesvirus infections such as HCMV and KSHV. Ultimately, these systems are refined to test and validate novel antiviral compounds.