Computational and Systems Biology

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Systems biology aims to build a working model of the cell by first mapping the network of interactions among biomolecules in the cell. While highly successful, this network-based view of the cell often treats biomolecules and their interactions as nodes and edges with little atomic details. Such details are crucial because atomic-level changes in the molecular circuitry can lead to large differences in cell behaviour, as often happens in evolution, development, and regulation. Specifically addressing this urgent need, the proposed research program of the Canada Research Chair in Computational and Systems Biology aims to construct accurate, genome-scale, atomic-resolution three-dimensional structural models for nodes and edges within protein-protein interaction networks in model eukaryotic species, in human, and between host and pathogen. This is achieved by developing key enabling computational technologies for high-resolution structural systems biology, and by collaborating with leading experimental systems biologists. These high-resolution structural models of the cell circuitry will then be used to probe evolutionary and design principles of biological networks within and between species, and to elucidate systems-level mechanisms of both human infectious and genetic diseases.The proposed research program integrates methodology development in structural systems biology with a wide range of fundamental applications in molecular biophysics, genetics, evolution, ecology, and disease, and represents the most comprehensive effort to elucidate high-resolution design principles of interactome networks. These quantitative insights can in turn be used to guide current efforts in protein engineering, synthetic biology, and treatment for genetic and infectious diseases, including COVID-19. In the long term, the proposed research program will build a multi-scale model of the cell circuitry, where the causes at the atomic level and the consequences at the organismal level can be modelled together in a unified framework. Such a multi-scale model of the cell is essential for transforming molecular cell biology into a predictive science, as well as for enabling rational design in biomolecular and cellular engineering.