Guest Seminar - Chemical Biology to Interrogate Protein Interactions in Living Cells

The precise and dynamic regulation of protein-protein interactions (PPIs) organize and control essentially every cellular process in multicellular organisms. Consequently, the aberrant PPIs are implicated in numerous disorders such as cancer and neurodegeneration. Moreover, the PPIs between human and microbiome greatly impact on human health and underlie the mechanisms of various infectious diseases. Therefore, comprehensive profiling of cellular protein interactions not only furthers the understanding of fundamental mechanisms of life sciences, but also facilitates deciphering pathogenesis of human diseases and developing novel therapeutic strategies.
However, it’s challenging to systematically profile the cellular protein interactions. For example, the conventional affinity-based purification approach is less efficient in capturing the transient and weak interactions, which dominate the whole interaction network and mediate crucial cellular events. Moreover, the exogenous bait proteins and ex-situ purification may destruct the cellular organization, resulting in a high rate of false-positive identifications and loss of context-dependent interactions such as those involved in pathogen infections with host.
In this talk, I will introduce how we combine bioorthogonal chemistry, photo-crosslinking, metabolic labeling, unnatural amino acid incorporation and quantitative proteomics to develop integrative chemical biology approach, tackle the abovementioned challenges, and thereby robustly identify dynamic, transient, and weak interactions in living cells.