Thomson Higher Ed  |  Thomson Learning |  Thomson

BioUpdates for March, 2003

by Andrew Tolley

We Are Not Alone

New Channels For Breast Cancer Research

Vitamin Supplement

From a Mickey Mouse Operation to Monkey Business

Molecular Fake Out

We Are Not Alone

One aspect of the complexity of the human body is the countless numbers and varieties of microorganisms that coexist within each of us in mutually beneficial symbiotic relationships. Our healthy survival pivots on balanced relationships with these much simpler organisms. Some estimates claim that there are actually 10 times as many microbial cells in an adult human as actual human cells. In addition, the estimated combined genome of all these microorganisms contains approximately100 times the number of genes than have been identified in the human genome. A more complete understanding of these organisms will inevitably lead to a greater understanding of ourselves and the potential creation of new generations of drugs. With this in mind, the sequencing of the genome of Bacteroides thethaiotaomicron represents a significant step. The just completed genome is reported in a recent issue of Science by researchers from the Washington University School of Medicine in St. Louis. This microorganism was selected for sequencing because of its prominence in the human intestine. Results are already revealing insights into how it assists digestion and resists the human immune system. The researchers have more than a gut feeling that one of the next major biological frontiers to be explored is the "microbiome" of the human digestive system.

References:

Xu, Jian et al (2003). A Genomic View of the Human-Bacteroides thetaiotaomicron Symbiosis. Science 299 (Mar. 28): p2074

Visit:

Science
http://www.sciencemag.org/cgi/content/abstract/299/5615/2074

back to the top

New Channels For Breast Cancer Research

Researchers from Cold Spring Harbor Laboratory in New York and Tularik Inc. using a gene discovery method called "Representational Difference Analysis" have identified a gene, KCNK9, which appears to play a significant role in the development of breast cancer. Focusing on a section of human chromosome 8 that seemed particularly prominent in breast cancer tumor development, the researchers have made significant connections between breast cancer and KCNK9, one of the two genes found in that area. Examining tissue from breast cancer tumors, they discovered significantly elevated levels of KCNK9 expression in 44% of the samples. Equally significant was the absence of any elevated KCNK9 expression in normal tissue samples. Subsequent experiments with mice confirm the link. Cancerous tumors developed in 60% of mice injected with cells with increased levels of KCNK9, whereas no tumor development was observed in mice injected with cells containing normal levels of KCNK9. This is a strong indication that KCNK9 plays a significant role in the development of breast and other cancers. Potassium channels are emerging as another mechanism for tumor growth. With that in mind, scientists now have new targets for drug research and therapy.

References:

Powers, Scott et al (2003). Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene. Cancer Cell 3 (Mar 03): 297-302.

Visit:

Cancer Cell
http://www.cancercell.org/cgi/content/abstract/3/3/297/

back to the top

Vitamin Supplement

Vitamin C (ascorbic acid) is a vital nutrient, providing defense against a variety of diseases and supporting a number of cellular functions. A diet including citrus fruits and leafy green vegetables will usually provide a plentiful supply of vitamin C, but many of the world's primary staples do not alone provide adequate vitamin C. Now new biotechnology developed by researchers at the University of California at Riverside could lead to vitamin-C enriched strains of crops. Such crops could provide improved nutrition for much of the planet's occupants, especially those in poorer countries. The line of inquiry has led to the development of biotechnology that increases the amount of the enzyme dehydroascorbate reductase (DHAR), which is responsible for recycling vitamin C in plants. If the recycling process is enhanced, vitamin C levels increase. Introducing the gene from wheat that encodes DHAR into corn, the researchers successfully elevated DHAR levels in corn. The net result was a significant increase in the amount of vitamin C found in the corn's grains and leaves. Subsequent tests saw similar results in other crops such as potatoes and tomatoes. The research team believes that the method can lead to elevated vitamin C in foods both naturally low or high levels of the nutrient. The biggest obstacle to the commercial development of such vitamin C enriched crops is most likely to come from those distrustful of genetically modified crops.

References:

Gallie, Daniel R., et al (2003) Increasing vitamin C content of plants through enhanced ascorbate recycling. Proceedings of the National Academy of Sciences 100: (Mar 18): 3525-3530.

Visit:

Proceedings of the National Academy of Sciences
http://www.pnas.org/cgi/content/abstract/100/6/3525

back to the top

From a Mickey Mouse Operation to Monkey Business

The completion of genomes for various organisms, including the human genome, has led to the evolution of a new field of biology, namely comparative genomics. Until now the human genome has only been compared to those of distant species such as mice and rats. Studies have yielded volumes of insight but these comparisons ultimately have their limits. Unfortunately, comparison to more closely related species such as apes, monkeys and other nonhuman primates has been difficult. The period of time since human evolution diverged from its closet relatives in the animal kingdom has essentially been insufficient to distinguish functional and nonfunctional DNA sequences in the genomes. Now a group of researchers from the Joint Genome Institute and the Lawrence Berkeley National Laboratory has pioneered a new technique that helps identify the more subtle differences between human and other primate DNA sequences. In a recent issue of Science, the researchers describe a technique called "Phylogenetic Shadowing" and how they have used it to begin comparing human and primate genomes. This technique essentially involves combining the DNA sequences of a variety of nonhuman primates into one composite sequence - the phylogenetic shadow - for comparison to the human sequence. This technique allows minor differences to emerge. Phylogenetic shadowing promises to shed great light on the different evolutionary paths followed by humans and other primates. It will also bring new insight, including a greater understanding of genetic risk factors for the study of certain cardiovascular conditions unique to primates.

References:

Rubin, Edward M. et al (2003). Phylogenetic Shadowing of Primate Sequences to Find Functional Regions of the Human Genome. Science 299 (Feb 28): 1391

Visit:

Science
http://www.sciencemag.org/cgi/content/abstract/299/5611/1391

Joint Genome Institute
http://www.jgi.doe.gov/

Lawrence Berkeley National Laboratory
http://www.lbl.gov/Science-Articles/Archive/JGI-primate-genome.html

back to the top

Molecular Fake Out

Among molecular biologists the protein NF-kappaB has a certain degree of notoriety, although it does perform some useful functions in the body. Evidence points to NF-kappaB promoting cancer cell survival, enabling the HIV virus to reproduce, and promoting the inflammatory process involved in such chronic diseases as rheumatoid arthritis. With a rap sheet like that it is no wonder it has become a target of research. At the Mayo Clinic in Rochester, Minnesota researchers have taken aim with an innovative approach, exploring how to use RNA molecules to act as decoys for the notorious protein. Experimenting with test tube models and then in live yeast cells, the researchers have succeeded in using RNA/NF-kappaB pairs to divert NF-kappaB from reaching DNA. By doing this they are able to prevent the protein from delivering its potentially disease-inducing message. Although the research is far from yielding some wonder RNA drug, the researchers are encouraged by their early success. After creating "smart" RNA that stuck to NF-kappaB in test tubes, they turned their attention to duplicating the process in the far more complex world of a living cell. Choosing yeast cells because of their similarity to human cells, they continued the experiment, and have observed RNA to have a significant decoy effect. The research team now hopes to develop an RNA decoy that can have a similar effect in mammalian cells. If that proves successful, some new drug therapies may well emerge.

References:

Cassiday, Laura A. & Maher III, L. James (2003). Yeast genetic selections to optimize RNA decoys for transcription factor NF-kB. Proceedings of the National Academy of Sciences. Online edition. (Mar 13): 1073

Visit:

Proceedings of the National Academy of Sciences
http://www.pnas.org/cgi/content/abstract/0736013100v1

back to the top