Model Systems for Infection and Immunity

Our Research

The MSYS research group focuses on driving advanced cell-based therapies to address unmet challenges in the treatment of bacterial and viral infections. Moreover, the team creates innovative model systems to investigate host responses to viral infections. Their work leverages tools from synthetic biology to enable predictable (epi)genetic manipulation of cells and animal models. This includes the development of advanced 2D and 3D (co-)culture systems as well as organoids to closely replicate in vivo conditions. Additionally, MSYS is advancing transgenic mouse models that allow precise spatial, temporal  and/or autonomous control of transgene expression.

1. Rewiring host response pathways for autonomous defense of bacterial and viral infections

The innate immune response serves as an early defense 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 signaling cascades to render infections visible and achieve therapeutic outcomes in a precisely controlled, autonomous on-demand fashion. Furthermore, the toolbox of synthetic biology is harnessed for modulating therapeutic responses against viral and bacterial infections, e.g. to amplify and/or sustain responses, thereby enhancing the overall outcome. Through this strategy, we also create theranostic cells that are able to recognize infection-specific signals and respond with efficient therapeutic actions that counteract infection and/or infection-related pathological responses.

2. Cell-mediated drug delivery and locally controlled release 

The systemic administration of drugs is often limited by toxic side effects in organs outside the target area. We develop strategies to deliver therapeutic agents specifically to sites of infection. For this purpose, we use micro- or nanoparticle systems that can be loaded with various drugs. As cellular carriers, we primarily employ macrophages, which we load with the drug particles in vitro. After injection, the loaded macrophages migrate specifically to sites of infection. Specific, locally restricted drug release is facilitated by applying external triggers such as diagnostic ultrasound or alternating magnetic fields. In addition, we develop strategies for the autonomous release of drugs. The goal is the targeted, on-demand release of therapeutic agents from particle-loaded cells specifically within the affected tissues.

3. Host’s response to human restricted viruses using advanced in vitro models

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.