Research
Innate immunity employs Toll-like receptors (TLRs) and Nod-like receptors (NLRs), both families of so-called pattern recognition receptors (PRRs), to detect a variety of different exogenous and endogenous insults. Exogenous insults include bacteria, viruses and fungi.. Upon engagement of their cognate microbe-derived molecular ligands, PRRs initiate distinct intracellular signalling pathways via receptor-proximal adaptor molecules, and subsequent NF-kB- and IRF-mediated gene transcription activates immediate innate immune responses and primes adaptive immunity. Since the discovery of human TLRs in 1997, other families of mainly cytosolic pattern recognition receptors (PRRs) have been described, for example, the RIG-I-like receptors (RLRs), Nod/NACHT-LRR-like receptors (NLRs) and AIM2-like receptors (ALRs). Together with TLRs, these PRR fulfill the important function of immune surveillance in the innate immune system and mark the first line of immune detection for most microbes. Apart from their role in infection, PRR have also been shown to be vital sensors of the various microbiomes found in different body sites, e.g. the intestine, and to be involved in sensing endogenous danger signals, e.g. accumulated metabolites or tissue breakdown products. As the initial recognition of microbes and endogenous danger signals by PRR has a profound influence on the timing, scale, type and extent of all subsequent innate and adaptive immune responses, PRR are nowadays recognized as pivotal immune regulatory molecules.
Although our understanding of PRR biology is steadily advancing, the principles of ligand recognition and intracellular signaling still remain poorly known. Little is also known about the differences of these signaling pathways in different human primary cell types or in normal versus transformed cells. Additionally, the functional and epidemiological significance of PRR single-nucleotide polymorphisms (SNPs) remains largely unknown. Therefore, our research focus is dedicated to delineating the function of PRRs from the molecular level, via the subcellular and cellular level, to cell-to-cell interactions in tissues and the organism as a whole.
Apart from contributing to a better understanding of the human innate immune system, we also aim to contribute to efforts hoping to define new targets of interventions based on PRRs. For this, we also cooperate with both clinicians at the local University Hospital as well as commercial enterprises.
Research Areas
- Structure-function relationships of ligand recognition and signal transduction in TLRs and other pattern recognition receptors (Area A)
- Functional relevance of Single Nucleotide Polymorphisms in TLRs and other pattern recognition receptors (Area B)
- Role of TLRs and other pattern recognition receptors in cancer and other diseases (Area C)
