The innate immune system is one of our first defense mechanisms against incoming pathogens. Concerted action of multiple pathways, among them autophagy and the type-I interferon response, efficiently facilitate prevention and/or clearance of microbes such as viruses.

Our previous studies already revealed that many factors involved in the induction of autophagy have (at least) dual roles. For example, TRIM23 upregulates both autophagy and type-I interferon upon infection. While the anti-viral properties of the type-I interferon are well-characterized, autophagy is a self-digestive homeostatic pathway with an emerging role within the innate immune system.

Concerted activation of innate immune defense mechanisms requires coordinated activation and modulation. Key factors that coordinate multiple anti-viral pathways represent hubs in the innate immune network, or short: immunohubs. These factors define our anti-viral responses and are thus major determinants of infectious diseases.  We aim to discover novel immunohubs to gain insight into regulation of our network of interconnected immune defenses and examine their interplay with viruses and explore therapeutic modulation of anti-viral innate immunity. 

To achieve this goal, we use a combination of state-of-the art methods from virology/molecular biology, (bio)chemistry and bioinformatics in our approach to explore the anti-viral innate immune system in an interdisciplinary manner. Among them are CRISPR, Next-generation-sequencing, proteomics, small compounds/peptide screens and derivatisation, advanced imaging techniques and bioinformatic analysis of large datasets.

Profilbild von Dr. Konstantin Sparrer

Dr. Konstantin Sparrer

Junior Group Leader

BMBF Nachwuchsgruppe Immunomod

While activation of autophagy during an infection is necessary to enhance anti-viral targeting of viruses, hyperactivation of autophagy leads to self-digestion and eventually cell death. Therefore, destructive defense mechanisms such as autophagy need to be tightly controlled. Excessive immune reactions significantly contribute to the pathogenicity of many viruses, for example the induction of AIDS by HIV-1. Therefore, we aim to identify and characterize key factors that keep excessive autophagy in check to ensure proper anti-viral action while protecting the host by providing negative feedback loops.

Viruses have evolved strategies to counteract our immune system, to enable currently circulating pathogens establish successful infections. Autophagy, like other innate immune pathways is known to be modulated by HIV-1. While the general consensus is that autophagy restricts viral growth, the underlying molecular mechanisms are still unclear. To unravel viral autophagy-modulation strategies we aim to dissect the interplay between the virus and autophagy.

Current knowledge indicates that exogenous modulation of autophagy may be an effective new approach to treat viral infections. The human peptidome provides a promising source for the discovery of as-yet-unknown physiological modulators of autophagy. Our goal is to identify, characterize and optimize peptides derived from the human peptidome that modulate autophagy and thus have an anti-viral effect. Furthermore, these peptides could also be important for the treatment of autophagy-related diseases such as cancer and neuropathies.