BioUpdates for November, 2002

by Andrew Tolley

Keeping Pace

A Spoonful of Sugar

Preserving Stem Cell Pluripotency

Proteome Probe

Adding a New Dimension to the Fossil Record

Keeping Pace

Each year about 250,000 Americans receive electronic pacemakers to put an extra beat in their step. Devices have become increasingly smaller and effective, but now scientists from John Hopkins University and the University of Maryland are on the verge of taking this branch of medical technology a step higher. Working with guinea pigs, the researchers have begun development on what can be best described as "biopacemakers." The team used a virus to deliver genes that altered the potassium balance in guinea pig heart cells. Heart muscle cells differ from pacemaker cells because the potassium channel is open; using gene therapy to block the channel enables these cells to act as pacemaker cells. Only a few days later, observations of the virus-infected guinea pig heart cells revealed alteration of the potassium channel and pacemaker activity were seen clearly on electrocardiograms. The success of creating these biological pacemakers in the guinea pigs is only a first step, but because of similarities between guinea pig and human heart physiology, the team is optimistic that similar success in humans is attainable. If this proves to be the case, such biologic pacemakers offer potential advantages. The need for invasive surgery would be reduced, as would the risk of infection, and pacemaker technology could be extended to those too small to have artificial devices implanted. What is more, biologic pacemakers could respond to the body’s needs, whereas artificial pacemakers cannot readily adjust to differing circumstances.

References:

Miake, J., Marban, E. & Nuss, B. (2002). Gene therapy: Biological pacemaker created by gene transfer. Nature 419 (Sept. 12th): 132-133.

Visit:

Nature

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v419/n6903/abs/419132b_fs.html

Abstract of above reference.

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A Spoonful of Sugar

Feeding the world’s ever-growing population is one of society’s great challenges. Part of the solution inevitably lies with science. Developing crops capable of resisting stress and with higher yields is a major objective of biotechnology. Although biotechnology is currently embroiled in controversy, researchers continue to explore ways of improving crop performance despite the objections to genetic engineering. Biologists at Cornell University are reporting significant progress in developing rice varieties far more resistant to environmental stresses such as drought, low temperatures, and salt. Working with a simple sugar, trehalose, known for its ability to help desert plants survive in very arid conditions, researchers have been able to introduce this sugar into Indica rice varieties using two genes from E. coli bacteria. So far the team has been able to reproduce the plants with the trehalose gene sequences over five generations, observing that these plants are more robust when subjected to environmental stress than nonengineered plants. What is more, these plants photosynthesize and utilize some soil nutrients more efficiently. In short, these plants have the potential not only to survive but also to provide higher yields. Although experiments have so far been conducted only with Indica rice varieties, the researchers are optimistic that similar success can be achieved with Japonica rice and a variety of other major crops such as wheat and corn. More research and safety testing is required before the transgenic rice seeds are ready for use. Although objections to these engineered plants are likely to arise, the researchers believe this strain might be more readily accepted due to the fact that the chemical composition of the edible parts of the plant remain unchanged. They also plan to put this new technology into the public domain rather than into commercial hands so that it is more readily available to those nations most in need.

References:

Garg, Ajay K. et al (2002). Trehalose accumulation in rice plants confers high tolerance levels to different abiotic stresses. Proceedings of the National Academy of Sciences (Nov. 27th).

Visit:

Proceedings of the National Academy of Sciences

http://www.pnas.org/cgi/doi/10.1073/pnas.252637799

Science Daily

http://www.sciencedaily.com/releases/2002/11/021126072734.htm

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Preserving Stem Cell Pluripotency

We know a lot about stem cells. However, there is still a lot to learn before complete understanding is achieved. One question that researchers at the University of Pennsylvania School of Medicine have begun to answer is just how do stem cells maintain pluripotency throughout embryonic development? What is it that enables them to pace themselves throughout embryonic development? The answer appears to lie at least partially with the Foxd3 gene. Manipulating mice embryos to lack Foxd3, the researchers discovered that when Foxd3 was absent the embryo could not maintain adequate stem cells to support continued development. Thus, the inner cell mass failed to expand enough to produce the embryo and other tissues. Confirmation of the gene’s role was evident when reintroduction of the gene enabled normal embryo development to continue. It is apparent that Foxd3 has a key role in determining the fate cell development in the embryo. Other genes, Oct4, Fgf4, and Sox2, also involved in controlling the pluripotency of stem cells still continued to be expressed in the absence of Foxd3. This indicates that Foxd3 operates alongside or after the expression of these genes. With the role of Foxd3 in humans closely paralleling mice, there is a lot to be learned from this study. Ultimately, the manipulation of the Foxd3 gene could lead to improved therapeutic applications and perhaps provide a method to prolong the "shelf life" of stem cells harvested for medical and research purposes.

References:

Hanna, Lynn A. et al (2002). Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo. Genes & Development 16 (Oct 15th): 2650-2661.

Visit:

Genes & Development

http://www.genesdev.org/cgi/content/abstract/16/20/2650

Abstract of above reference.

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Proteome Probe

We are all familiar with the "genome" (the full sequence of an organism’s genes) and its potential to fight disease. Stemming from the field of genomics, scientists now speak of the "proteome," the full assemblage of proteins in an organism, and how this can be used to combat disease. In fact, Duke Clinical Research Institute along with two Swiss corporations, GeneProt and Norvartis Pharma AG, have announced that they are embarking on a major study using proteomics to unravel the mysteries of heart disease, and the role of proteins in one of the globe’s leading killers. Using Duke’s Databank for Cardiovascular Diseases, the research group has obtained a large blood sample from a group of heart disease sufferers that meet very specific criteria. The blood from each individual has been combined in order to reduce natural variations and provide a substantial sample. Likewise, a blood sample from a group of healthy individuals meeting the same criteria also has been created. Using the technology of the Swiss companies, each blood sample is being analyzed for protein content. The volume of blood being used in the sample is unprecedented in the field and will hopefully provide the most complete proteome possible, allowing for detection of even the scarcest proteins. When the analysis is complete, the assemblage of proteins from both groups will be compared. Differences in the concentrations of proteins will hopefully finger which proteins appear to be implicated with heart disease, either by their presence or by their absence. This study is very much a work in progress, with the analysis of samples still continuing. If successful, the study will surely pave the way for other proteomic studies designed to understand other diseases.

Visit:

GeneProt

http://www.geneprot.com/scripts/index.asp

Duke University Medical Center

http://news.mc.duke.edu/news/article.php?id=5814

Human Proteomics Initiative

http://us.expasy.org/sprot/hpi/
http://us.expasy.org/proteomics_def.html

e.protemics.net

http://www.e-proteomics.net/

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Adding a New Dimension to the Fossil Record

For the most part, what we understand about animal evolution is based on interpretations of the physical aspects of fossils. Comparisons of bone size and morphology have been key to forming our picture of the passage of evolution. Now collaborative work by researchers from the Universities of Oxford and Newcastle in England and Harvard and Michigan State in the U.S. has produced a major breakthrough in the science of paleontology. Using sophisticated techniques such as matrix-assisted laser desportion ionization mass spectrometry, the team has succeeded in recovering mitochondrial DNA from the 55,000-year-old remains of bison from Siberia and Alaska, as well as the complete sequencing of osteocalcin, a bone protein. Calculations based on this work indicate that DNA can survive approximately 100,000 years but that proteins may survive as long as 10 million years. Because changes in DNA can be inferred from proteins, the team believes that there is now the potential to use biochemical information from much older fossils, thus providing far more reliable and subtle methods of genetic analysis to be applied to fossils rather than traditional morphological studies.

References:

Nielsen-Marsh, Christina M. et al (2002). Sequence preservation of osteocalcin protein and mitochondrial DNA in bison bones older than 55 ka. Geology 30 (Dec.): 1099–1102.

Visit:

Geology – Journal of the Geological Society of America

http://www.gsajournals.org/gsaonline/

Visit December issue to find abstract of above reference.

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