Research Program Overview

In most natural environments, bacteria live in large, highly organized communities of cells known as biofilms. Biofilms have been linked to human infections, contamination of aquatic environments, and economic losses in industrial settings, leading to a surge in biofilm research over the past decade. Although work on biofilms is still in its infancy, research on the model organism Myxococcus xanthus has been extremely useful in revealing some of the intricacies of life within a biofilm. The success of research on this organism can be attributed to the fact that it is easily grown in a laboratory setting, it has multicellular developmental cycle that is rapid and well characterized, and it is amenable to genetic and molecular analyses. In my research group, we use the biofilm formed by M. xanthus to understand how large groups of cells communicate with one another, and how this cellular dialogue coordinates the temporal and spatial expression developmental genes.

Bacterial-derived natural products have been a major source of new drugs in all therapeutic areas and the inspiration for many chemically synthesized drugs. Two major groups of natural products are the bacterial-derived polyketides (PKs) and non-ribosomal peptides (NRPs), which have been crucial sources of therapeutics such as antibiotics and anticancer agents. There is an enormous diversity of PK and NRP natural product biosynthetic gene clusters in bacterial genomes, but only a small fraction of the corresponding compounds have been identified and characterized. The discovery of new PKs and NRPs has been plagued by two major problems:

  1. The vast majority of bacteria that have PK and NRP gene clusters in their genomes are difficult to culture or uncultivatable
  2. Heterologous expression systems yield low levels of PK and NRP biosynthetic gene transcription and correspondingly low or undetectable levels of product formation.

My lab is studying the regulation of PK and NRP genes and using this information to develop heterologous systems that will express PK and NRP gene clusters from many bacterial species.