Research project

Systems microscopy-based drug target discovery in pathogen-mediated inflammatory response signalling

Our approach will be to establish human iPSC-based fluorescent reporter cell lines for the NF-kB signalling pathway; alternative signalling routes will also be included. We will extensively characterize these reporter cell lines for application in systems microscopy approaches. Thereafter we will differentiate these iPSC lines into different cell lineages, including liver hepatocytes, cardiomyocytes and neuronal cells using established approaches. In these different lineages we will quantitatively assess the dynamics of downstream signalling activation by various PAMPs and cytokines. In parallel in the different lineages we will assess the transcriptomics responses using high through RNAseq-based transcriptomics. In selected differentiated cell models we will unravel the signalling components that may impact on improving host defence against pathogens. This will be based on CRISPR/Cas approaches making advantage of previous identified candidate drug targets.

Duration

2017 - 2021

Contact

Bob van de Water