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NIH grants enable energy studies

Robert G. Kranz, Ph.D., professor of biology in Arts & Sciences, has been awarded two grants from the National Institutes of Health (NIH) to study pathways in bioenergy conversion. One is a long-term NIH R01 renewal titled "Cytochrome c Biogenesis", and it is for $1,203,250. It started on August 1. The renewal award means that NIH has funded Kranz continuously for 22 years.

The U.S. Department of Agriculture, U.S. Department of Energy, National Science Foundation and Monsanto also have supported the Kranz group during the past twenty years.

Cytochrome c is a protein with the heme cofactor covalently attached to it. Cytochrome c is crucial for energy production in many bacteria and higher organisms, including humans and it is one of the most rigorously researched cellular components over the past 60 years. It is essential for the production of ATP (adenosine triphosphate), the compound that energizes all organisms.

The road the cell takes to make cytochrome c is called the biogenesis pathway. There are three different pathways which organisms use to assemble a c-type cytochrome, and in a 1998 review Kranz and colleagues termed these "systems I, II, and III." Kranz discovered the most complex one, called System I, and published the results of genetic studies beginning in 1989. These results described many of the genes required for the system I pathway.

Current members of the Kranz group include Cindy Richard-Fogal, Ph.D., research scientist in biology, and Elaine Frawley who have engineered two of the three biogenesis pathways in E. coli. Now they will engineer the third, which is naturally present in humans. Additionally the function and mechanisms behind each protein in the pathways will be studied.

The second NIH grant, an R21 award of $190,000, is to further develop a screen to find inhibitors of the pathways. Since bacteria have either system I or II but humans do not, inhibitors could be potential antimicrobial agents against certain infectious diseases. Once the screens are developed, the Kranz group will collaborate with Lucile White, Ph.D. and Krister Wennerberg, Ph.D. at the Southern Research Institute in Birmingham, Ala., which is a center for NIH's Roadmap for Medical Research Initiative on high throughput screening. Importantly, the grant award provides access to the NIH Molecular Libraries Screening Center Network (MLSCN), and to experts like White and Wennerberg. The NIH "library" of chemicals is composed of 100,000 different small molecules.

Kranz has taught undergraduates every year at Washington University. He taught microbiology to juniors and seniors for 14 years, and freshman biology for four years. Kranz is currently teaching a four- credit, laboratory course in DNA manipulations (Bio 437), which meets for eight hours on Friday and Saturday and one hour on Wednesdays.

Two of the projects for the class, comprised of juniors and seniors, are related to bioenergy conversion, whereby the students are cloning and knocking out genes for many cytochromes. These cytochromes are potentially involved in bioelectricity generation. This work also is linked to the biogenesis pathways, and began as collaboration between the Kranz group and Lars Angenent, Ph.D., assistant professor of chemical engineering. Miriam Rosenbaum , Ph.D., a postdoctoral researcher in the Angenent lab and Rachel Lee, a biomedical engineering undergraduate, and Elaine Frawley, a graduate student, both from the Kranz group are piloting these studies in their spare time. The long term goal is to engineer "electrical nanowires" into E.coli to make an efficient E.coli biofuel cell.

"We are the experts in genetic engineering of such nanowire proteins and they are the microbial fuel cell experts, a perfect fit that has been a fun collaboration, "said Kranz. "Once we have the preliminary data, our plan is to write up a joint grant on extending these efforts. The grant preparation and proposal is also intended to provide valuable experience for team members who are on track to become teachers and researchers. "

Kranz currently has five undergraduate students working in his research lab and he takes pride in training them, saying that, by the time they graduate, they are as good as most advanced graduate students at designing, implementing, and analyzing experiments. He said that the next few years should be exciting for all on the cytochrome projects.


Contact: Tony Fitzpatrick
Washington University in St. Louis

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