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Cellular Aspects of Host-Pathogen
Interactions

Since viruses are dependent on the host cell machinery to replicate and they also have to overcome intrinsic and innate cellular restrictions, understanding the molecular mechanism of both host and innate immune factors will significantly facilitate the development of novel therapeutic and vaccination strategies aimed at combating current and emerging pathogenic viral infections.

We seek to gain insights into the dynamic interactions affecting virus replication, with the primary goal of elucidating innate immune factors. We are particularly interested in novel host interactions with reverse-transcribing and RNA viruses (HIV, HBV, and Ebola). Our interests lie in identifying novel regulators of innate pathways and understanding how viruses are recognised by the innate immune system.

We discovered numerous cellular proteins and pathways affecting the replication of viruses by using genome-wide arrayed RNAI screening technologies complemented by proteomics and meta-analysis approaches (König et al., Nature 2010; König et al., Cell, 2008; Tripathi et al., Cell Host & Microbe, 2015). We identified a novel negative regulator of the STING-mediated interferon response (Guo et al., Cell Host & Microbe, 2016) and analysed the molecular regulatory mechanism of a novel factor that restricts HIV and HBV replication (Schott et al., Nature Communication, 2018). Our current focus is on establishing novel approaches such as arrayed CRISPR/Cas9 technology to complement the repertoire of genome-wide approaches and IPSC technology to provide suitable primary models for analysing innate immune pathways (Fuchs et al., Stem Cell Research, 2019).

Furthermore, our lab has expanded to include data scientists (led by Dr Liam Childs), that focus on next-generation sequencing analysis and machine learning approaches. An additional subgroup addresses the application of machine learning and text mining approaches to support regulators and assessors at the Paul-Ehrlich-Institut.