Mathematical Biology Laboratory

Projects and Collaborations

We have several on-going projects, with collaborators both on campus and across the world. 

Emprical growth laws in bacterial physiology 

Exponential growth imposes constraints on resource allocation within the organism. By tracking the abundance of ribosomes (which drive protein synthesis) and expression of unregulated proteins under a variety of growth perturbations, together with Terry Hwa (UCSD) we have uncovered a series of 'growth laws' that provide insight into indirect regulation of endogenous and synthetic genetic elements within a growing cell. 

The coarse-grained view of physiology afforded by the 'growth laws' provides a new approach to the optimization of heterologous protein expression for biomanufacturing processes (in collaboration with Perry Chou (Chemical Engineering, UWaterloo)), elucidation of how infection virulence impacts apparent susceptibility to antibiotic treatment (in collaboration with Rosalind Allen (UEdinburgh)), and design-principles at work in the earliest stages of life on this planet.

Modelling DNA replication in the eukaryotic cell cycle

Misregulation of the cell division cycle occurs in the development of most cancers. Together with Bernie Duncker (Biology, UWaterloo) our group has developed a differential-equation based model that describes the initiation of DNA replication in the eukaryotic cell cycle. Ongoing work involves characterizing the dynamics of cell cycle checkpoints in our model organism, Saccharomyces cerevisiae.

Model-based design of bioprocess operations

With Marc Aucoin (Chemical Engineering, UWaterloo), we are developing stochastic models of viral infection events in a virus-delivery based protein-production process. Genes for the recombinant protein are delivered to insect cell hosts via infection by engineered herpes virus. Our model aims to predict the dynamics of infection in the culture, with the aim of reducing the cost of pre-process viral production while maintaining product yield.

Elimination of antibiotic resistance plasmids

Antibiotic resistant bacteria now present a significant health challenge. In many instances, the genes responsible for resistance are carried on an extra-chomosomal genomic element, called a plasmid. Building on initial modelling efforts, we are investigating a means of eliminating plasmids from bacterial populations by taking advantage of the copy-number-control mechanisms that naturally limit their abundance in individual cells. This work is coupled to our efforts to model the environmental spread of antibiotic resistance plasmids through wastewater treatment plants, begin carried out in collaboration with Chris Yost (URegina).

Selected Publications

M. Scott, P. Greulich, M. Evans, R. J. Allen (2015) Growth-dependent bacterial susceptibility to ribosome-targeting antibiotics. Molecular Systems Biology 11: 796. [pdf].

M. Scott, S. Klumpp, E. M. Mateescu and T. Hwa (2014) Emergence of robust growth laws from optimal regulation of ribosome synthesis. Molecular Systems Biology 10: 747. [pdf]