Stretching Neurons Induces Growth
They say that tension is bad for the nerves, but it turns out that a little applied tension might be good for nerve cells. Researchers at the Medical Center have been able to grow nerve cells, or neurons, by stretching them--offering a new means of bridging damaged areas of the nervous system. Using a motorized device to slowly pull connected neurons away from each other, Penn researchers have discovered that the connecting nerve fibers, called axons, grow longer in response to the strain. In addition, the researchers have grown these elongated nerve fibers directly on a dissolvable membrane, ready-made for transplant. Their discovery is published in April's Tissue Engineering. "Most studies have examined axon growth in terms of how axons sprout from one neuron and connect to another. But there is an equally important form of axon growth that has been overlooked, the growth of axons in terms of the growth of the entire organism," said Dr. Douglas Smith, lead researcher on the project and associate professor of neurosurgery. "In a way, stretching is akin to how nerve cells grow in developing children--as they get taller their axons get longer." These findings, which have evolved from Dr. Smith's ongoing research into how neurons respond to their environment, also represent a departure from other methods of restoring neural pathways in spinal cord injuries by bridging over damaged tissue. "Once somebody's nervous system is already formed, further outgrowth could cause mass confusion, so the body actively produces chemicals that stop axon growth" said Dr. Smith.
Detecting Proteins with IDAT
Scientists may have identified the genes in the human genome, but proteomics is the growing field of research that describes how proteins encoded in those genes work. Researchers at the School of Medicine have created the first new technology for the proteomic era, a technique sensitive enough to detect individual proteins and robust enough to screen hundreds or thousands of molecules in mass automation.
The technique, called IDAT, has a variety of potential uses from detecting cancer earlier to sifting through samples of molecules to find new candidates for drug research. In the April 23 Proceedings of the National Academy of Science, the researchers describe how they used IDAT to identify a protein marker for breast cancer at a resolution up to nine orders of magnitude more powerful than conventional techniques, and explain how the technique can be further refined.
"Nine orders of magnitude is a significant jump. If we were discussing computers, we would be talking about the differences between bytes and gigabytes," said Dr. Mark I. Greene, professor of pathology and laboratory medicine. "IDAT has the potential to do for proteomics what PCR did for genomics in the last two decades."
"IDAT can detect proteins earlier, faster, and with more sensitivity than other methods," said Dr. James Eberwine, professor of pharmacology and psychiatry. "Tumors, for example, often shed particular proteins at an early stage and the sooner you can detect the proteins, the sooner you can treat the cancer."
Dr. Eberwine and Dr. Greene worked with colleagues--Dr. Hong-Tao Zhang, Janet Estee Kacharmina, and Kevin Miyashiro--to develop the IDAT technique and further refine it for broader applications.
For patients, IDAT could enable doctors to routinely screen blood samples for early disease indicators, returning results in a matter of hours instead of the days or weeks it often takes now for the most complicated tasks.
The research that developed IDAT has been funded by NIH and The Leonard and Madlyn Abramson Family Cancer Research Institute.
Ancient Frog Named for Professor
Two former students have named a 75-million-year-old frog species in honor of vertebrate paleontologist Dr. Peter Dodson.
Dating to the Cretaceous era, the new-found species, Nezpercius dodsoni, also commemorates the Nez Perce tribe of Native Americans. The fossil frog was unearthed in central Montana, near where the tribe crossed the Missouri River as it was pursued toward Canada in 1877.
Dr. Dodson, professor of anatomy in the School of Veterinary Medicine and professor of earth and environmental science in SAS, also conducts fieldwork in Montana--as well as Egypt, China and Argentina--as part of his studies of dinosaur remains.
The honor came as a surprise to Dr. Dodson, who first learned of it while reading a paper in the March issue of the Journal of Vertebrate Paleontology that described the new-found species.
The paper indicates that the "species name honors Peter Dodson for his contributions to paleoecological research in the Judith River Formation."
Richard W. Blob, one of the paper's five authors, a 1992 Penn graduate who did fieldwork with Dr. Dodson in Montana for several years, is now a postdoctoral researcher at the Field Museum of Natural History in Chicago.
Another author, Dr. Catherine A. Forster, was a doctoral student under Dr. Dodson, receiving her Ph.D. in 1990. She is now associate professor of anatomy at SUNY at Stony Brook.
Progenitor Cells' Protective Effect
Penn researchers have found that by transplanting neural progenitor cells into rats with brain injuries they can restore brain function and lessen further brain damage. Their findings are the first to demonstrate the ability of progenitor cells, grown in culture, to restore cognitive and motor function while rescuing brain cells from the cumulative effects of traumatic brain injury. The results of the research, led by Dr. Tracy K. McIntosh, of the School of Medicine, is presented in the May issue of the Journal of Neurosurgery.
"In this study we have determined how progenitor cells--a more developed type of stem cell--cannot only restore function, but counteract the secondary injuries that result from brain trauma" said Dr. McIntosh, professor of neurosurgery, bioengineering, and pharmacology and director of the Head Injury Center.
Unlike stem cells, which are completely unspecialized, progenitor cells have begun the path to specialization. In this study, the stem cells used have become progenitor brain cells, although they have not yet developed into a specific type of brain cell. The researchers found that the progenitor cells were able to survive in the hostile environment of the injured brains and actually promote the reconnection of brain pathways that were destroyed during trauma. These Nerve Growth Factor (NGF)-producing cells, had the effect of protecting against further damage in the brain.
The destruction of brain tissue does not stop after the initial head impact. Cells in the brain weaken and continue to die from the cumulative effects of the injury in a process called apoptosis, a series of internal reactions that causes the cells to die.
The research is a collaborative effort between researchers at Penn and counterparts in Sweden and Spain. Other Penn researchers include Dr. Matthew F. Phillips, Dr. Philipp Lenzlinger, Dr. Grant Sinson, and Dr. M. Sean Grady.
Plant Genes: Less Pesticides
Penn biologists have identified the first gene known to mediate the maturation of plants from a juvenile stage to adulthood. The discovery could lay the foundation for crops that repel pests by taking advantage of natural differences between younger and older plants, reducing farmers' reliance on pesticides while sidestepping the controversy surrounding produce engineered with the addition of genes from other species. The work is detailed in the March 23 issue of Science.
While versions of the new-found gene appear in species from yeast to humans, the findings represent the first demonstration of function in a higher organism, in this case the plant Arabidopsis thaliana. The gene, called squint because mutant seedlings' pointy, elongated leaves resemble squinting eyes, is believed present in all flowering plants, including such valuable crops as corn, tomatoes and soybeans.
Capitalizing on the natural morphological and biochemical differences that characterize these crops at different stages of development could further curtail pesticide use, said lead author Dr. R. Scott Poethig, while avoiding the highly contentious practice of importing genes from other species, conventionally known as genetic engineering.
"Many pests find either juvenile or adult plants unpalatable, so tinkering with the genes that control plant development could render crops uninviting," said Dr. Poethig, a professor of biology in the Plant Science Institute.
For example, Dr. Poethig said, mature leaves on corn and rice plants are more resistant to pests than their more tender counterparts, and only the juvenile, lowermost branches of birch, willow and aspen trees found in Arctic regions are distasteful to the snowshoe hares that might otherwise graze on them.
"Mutations like squint allow you to use a plant's natural resistance to disease, and other naturally occurring developmental traits, in different ways," he said. "Instead of introducing a foreign gene from another species, one should be able to isolate mutations in squint-like genes that cause a normal, desirable trait to be expressed at a different time in development."
Squint encodes the protein Cyclophilin 40 (CyP40). CyP40's biochemical function is already known--in human beings, it's part of a complex that blocks receptors for hormones like estrogen and progesterone--but its physiological role in higher organisms has remained a mystery.
Dr. Poethig's work with plants mutant in squint indicates that CyP40 affects secondary characteristics of adult plants, like the shape and biochemical properties of leaves, but not sexual maturation or flowering. The very first leaves that appear on a squint mutant are toothed and angular, like mature leaves, rather than stubby and rounded like juvenile leaves. The timing of sexual maturity and flowering, though, is not affected.
Dr. Poethig's co-authors are Tanya Z. Berardini, Krista Bollman and Hui Sun, all of Penn's Plant Science Institute. The work was funded by the NIH and the NSF.
Almanac, Vol. 47, No. 35, May 29, 2001