Exploring Functional Landscapes Of The Cell Through The Lens Of Protein Interactome Networks

Abstract

Proteins function primarily by physically interacting with other proteins. As such, maps of these interactions, called protein interactome networks, can be valuable resources to help us better understand fundamental biological processes. I generated FissionNet, the first proteomewide interactome network of the model fission yeast, Schizosaccharomyces pombe. FissionNet comprises 2,278 high-quality interactions, of which >90% were previously unreported in S. pombe and ~50% were previously not reported in any species. Moreover, FissionNet unravels previously unreported interactions implicated in processes such as stress response, gene silencing, and pre-mRNA splicing. From the evolutionary perspective, by comparing FissionNet with the interactomes of the budding yeast, Saccharomyces cerevisiae and of human, my colleagues Jishnu Das and Michael Meyer find that interactions are preserved better between conserved protein pairs of S. pombe and human compared to S. cerevisiae and human. To further dissect the preservation of conserved interactions, I performed large-scale cross-species interactome mapping to demonstrate that coevolution of interacting proteins is remarkably prevalent, a result with important implications for studying human disease in model organisms. Both Chapters 2 and 3 detail work done with regards to the S. pombe protein interactome network.