Gene Networks in Bacillus subtilis

Kenyon Applebee, PhD

My current project involves discovering phenotype changes caused by interactions between distant genetic elements in Bacillus subtilis. Distant epistatic and pleiotropic interactions are increasingly recognized as frequent and pervasive in the genome, especially at network levels that produce complex behaviors and phenotypes. These interactions indicate biological networks are highly interconnected, operate with non-linear dynamics, and have far more degeneracy than is currently recognized.

My current project is to search for distant epistatic interactions in Bacillus subtilis. I have selected a small set of genes representing a wide variety of biological functions and I am generating all pair-wise combinations of double knockouts within this set. I will then quantitatively measure a broad range of phenotypes expressed by this set of strains to discover epistatic interactions. We will then produce gene expression profiles on strains exhibiting epistasis under the relevant growth conditions. While each singly discovered epistatic interaction will likely involve a large number of expression changes, with little to distinguish causal from secondary or incidental expression changes, we hope to discover a sufficient number of epistatic interactions that the dataset as a whole can be analyzed to establish boundary conditions involved in producing particular phenotypes. Eventually, we will develop a theoretical framework that captures the properties that distinguish classes of output states (phenotypes), and then test their predictive value. In the future we also intend to extend this approach to additional single-celled organisms.