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Diana M. Downs

Professor of Bacteriology

Address:

6472 Microbial Sciences Building

Telephone:

265-4630

Email:

downs@bact.wisc.edu

Research Fields:

Microbial Genetics

Molecular Genetics

Genomics

Research Interests

biochemical genetics, bacterial metabolism, global approaches to uncovering protein function.

Research Description

Metabolic Integration in a Bacterial Cell

At the core of any living cell is metabolism; the sum total of all the biochemical processes contributing to cell function. Coordination of these processes results in the physiology we associate with each organism, from bacteria to humans. Thus, a solid understanding of metabolic integration is critical for the advancement of many biological disciplines. The major goal of research in the Downs’ lab is to expand the basic knowledge of both the metabolic components of a cell and their interactions. The strength of the lab is in classical genetic analyses, a global, logical, phenotypic driven approach that allows the organism to reveal significant metabolic connections. To extend our findings to the molecular level, we take advantage of classical and emerging technologies, including biochemistry, molecular biology, genomics, and bioinformatics. In the last ten years, we have developed a model system to identify metabolic connections in vivo in Salmonella enteric serovar Typhimurium that utilizes the biosynthetic pathway for the essential vitamin thiamine as a “nucleation point”.

At this point, one major area of focus in the lab involves the process of Fe-S cluster synthesis and repair. Specifically we are probing the function of 4 proteins that we identified in our work that appear to be “accessory” proteins for this process. Each of the proteins is highly conserved, yet no biochemical function in any organism has been described. Secondly we are dissecting a broadening network of pathways that are affected by a protein we identified, YjgF. This protein also is distributed throughout the three domains of life, 5 molecular structures have been determined, and yet no known biochemical function has been attributed to this family of proteins. Thus far, lack of this protein affects at least respiration, branched chain amino acid, trptophan and thiamin synthesis. The biochemical mechanism by which these effects are mediated is under study in the laboratory.

Representative Publications

• Schmitz, G. and D.M. Downs. 2004. Lesions in yjgF result in a decreased specific activity of Transaminase B (IlvE) in Salmonella enterica serovar Typhimurium. J. Bacteriol. 186:803-810.
• Skovran, E. and D.M. Downs. 2003. Lack of ApbC or ApbE proteins results in a defect in Fe-S cluster metabolism in Salmonella enterica serovar Typhimurium. J. Bacteriol. 185:98-106.
• Ramos-Solis, A.I. and D.M. Downs. 2003. Anthranilate synthase can generate sufficient phosphoribosyl amine for thiamine synthesis in vivo in Salmonella enterica. J. Bacteriol. 185:5125-5132.
• Allen, S., J.L. Zilles and D.M. Downs. 2002. Metabolic flux in both the purine mononucleotide and histidine biosynthetic pathways can influence synthesis of the hydroxymethyl pyrimidine moiety of thiamin in Salmonella enterica. J. Bacteriol. 184:6130-6137.
• Gralnick, J.A., and D.M. Downs. 2001. Protection from superoxide damage associated with an increased level of a particular bacterial protein. P.N.A.S. 98:8030-8035.