Kimberly Reynolds, Ph.D.

Understanding the Organization and Evolution of Cellular Systems

The ability of a cell to grow, divide, and respond to the environment depends upon the coordinated action of many underlying molecular parts. A large body of past work has defined the identity and activity of many of the parts taken individually, but we are still left with a deep unexplained complexity in understanding how such cellular systems work and evolve as a whole — especially in terms of general principles that transcend the details of individual cell types.

In our research, we aim to extend our current knowledge of individual cellular components to the understanding, prediction, and control of global cellular behaviors.

The growing collection of complete genome sequences presents a major opportunity to address this problem. By studying evolutionary statistics across many genomes we hope to decipher the global pattern of functional constraints between genes, and distinguish interactions critical to core cellular function from those that occur idiosyncratically within particular species.

We hope that this work will lead to a set of statistical rules that describe the assembly of functioning cellular systems. Central to our approach is the premise that conservation and co-evolution between different properties of genes can be used to map system-independent functional interactions at a genome-wide scale.

Our basic strategy is two-fold:

  • To carry out mathematical analyses of co-evolution and conservation across genomes, and
  • To test the necessity and sufficiency of this information by the design and experimental characterization of non-trivial cellular systems.