The Role of Mass Balance and Gene Dosage in Protein Interaction Network

This work presents two separate investigations based on a similar theme: that the topology of protein-protein interactions should in part be predictive of a protein's sensitivity to dosage. The first investigation focuses on individual multi-protein complexes examining whether protein complex topology is a determinant of dosage sensitivity. Mass balance equations are used to compute the response of complex formation to varying amounts of each component protein. The computed response is then related to experimental data in the form of fitness of hetezygous deletions, overexpression phenotypes, and protein expression noise. The second investigation focuses on larger protein interaction networks and looks specifically at proteins that interchangeably bind multiple other proteins. A series of simple networks is used to gain insight into changes in the amount of unbound protein upon overexpression, again using equations describing mass balance. Predictions of the simple models are then validated with experimental data.