William Page

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Overview

Research

In looking at my research program since 1973, I realize that I have always been treating bacteria very badly and then trying to understand how they respond to these imposed stresses. Azotobacter spp, especially Azotobacter vinelandii, have been the focus of this abuse which has included iron limitation, nitrogen limitation and oxygen toxicity. Iron-limited growth has become a focus, as it induces genetic competence in A. vinelandii, induces iron-uptake systems, promotes capsule formation (alginate), and eventual encystment (differentiation) of the cells. I am particularly interested in the characterization and regulation of iron-uptake systems and iron chelators (siderophores). Student projects involve whatever is required to reach a solution to problems posed, including studies of cell structure, physiology, natural products chemistry, moleculary biology and genetic regulation. We consider these studies of interest to basic science and understanding of how cells respond to and survive stress, and of interest because Azotobacter spp. are common nitrogen-fixing bacteria which improve soil fertility throughout the world.

In the course of these studies, an iron-regulation mutant was discovered which produced large amounts of the polymer poly-b-hydroxybutyrate. Since this material and its copolymers have considerable value as natural biodegradable plastics, this mutant has launched a spin-off project into the control of bacterial production and biodegradation of these polymers (collectively known as polyhydroxyalkanoates). Continuing work in this area concerns the control of metabolic pathways leading to polymer and copolymer production.

A great adventure that we have embarked on this year (2001/02) with collaborators in the USA, UK, Mexico, & Norway is the complete sequencing and annotation of the Azotobacter vinelandii strain UW genome.  There are many things we know about A. vinelandii, after the collective work of 100’s of scientist throughout the world, over the last >90 years. But we only know the identity of about 200 genes out of a potential 4000 and there are so many questions that could be answered directly or facilitated by genomic knowledge.  We were very fortunate to have this sequencing project included in the 2nd genome campaign of the DOE-JGI (Department of Energy Joint Genome Institute, USA) and the scaffold assembly and automated annotation of the genome is progressing under the care of ORNL (Genome and Systems Modeling Group, Oak Ridge National Laboratories, TN).