Our research focuses on interactions between short linear motifs and peptide binding domains and aim to contribute with novel insights into the human protein-protein interaction networks in health and diseases. Our research is interdisciplinary and combines biochemical and biophysical methods with bioinformatics and cell-based assays. In particular, we use proteomic peptide phage display to identify interactions of potential biological relevance, bioinformatics to filter for relevant binders and in vitro affinity measurements and cell-based assays for detailed analysis of key interactions.
Interaction profiling through proteomic peptide phage display
A significant part of the human proteome is intrinsically disordered. These regions are enriched in short motifs serving as docking sites for peptide binding modules. Peptide-motifs interactions are crucial for the wiring of signaling pathways. These important but transient interactions are difficult to capture through most conventional high-throughput methods. We apply a novel approach for the large-scale profiling of domain-motifs interactions called Proteomic Peptide Phage Display (ProP-PD) (Ivarsson et al, 2014, Sundell & Ivarsson, 2014). The method allows the interrogation of domain-motifs interactions on a proteome-wide scale. ProP-PD can be used to search for protein-motif interactions of potential biological relevance on a proteome wide scale and it provides information that is complementary to other high-throughput methods.
Systems biology of SLiM-based host-pathogen interactions
Viruses exploit a variety of cellular mechanisms to hijack cellular protein-protein interactions (PPIs). Host-pathogen PPIs facilitate their uptake into the cell, the take-over of the host cell machinery, and contribute to the virulence, the immune response escape and the length of diseases. To understand the molecular basis of virulence, fitness and pathogenesis, and to be identify novel targets for therapeutic intervention, it is thus crucial to systematically explore the host-pathogen PPIs. With the support of the Swedish Foundation for Strategic research we are therefore taking a hybrid systems biology approach to explore the wealth of pathogen short linear motifs and their interactions with host proteins.