Using the Planarian Flatworm to Study Ways to Repair Human Tissue and Organs
What can the planarian -- a free-living, freshwater flatworm with remarkable regeneration abilities -- teach scientists about cellular development and how to develop better ways to medically repair human tissue, organs and body parts that cannot be naturally replaced when damaged by trauma or disease?
Plenty, says noted researcher Alejandro Sánchez Alvarado. He should know. Alejandro, over the last eight years, has almost single-handedly established the planarian (Schmidtea mediterranea) as a powerful new model system to study the molecular mechanics of regeneration. Regeneration is an emerging research field that is exploring how medical science can benefit from learning how certain species grow entirely new tissue or body parts when these are lost to injury, amputation or illness.
A cellular and molecular biologist by training, Alejandro is a scientific investigator with Howard Hughes Medical Institute, and the Stowers Institute for Medical Research.
"Insight into regeneration can shed light on how higher organisms, including humans, develop biologically," he explains, "and provide further understanding of such medical conditions as spinal cord injury, loss of limbs, and the loss of neurons due to stroke and degenerative diseases like Parkinson's and Alzheimer's."
Regeneration has fascinated philosophers and scientists since the beginning of history and civilization, including playing a prominent role in nature and Greek mythology. However, biologically, the phenomenon of regeneration still remains mostly a mystery. Scientists know that every day, the human body replaces an estimated 10 billion cells lost to injury or ordinary cellular housekeeping. More dramatically, salamanders, flatworms, and hydra, among other organisms, grow entirely new body parts when these are lost to injury or amputation.
But a lack of good model organisms and effective techniques has, for the most part, managed to keep regeneration a biological conundrum. At least until Alejandro began researching the planarian in earnest. Over the past seven years, he and colleagues have developed methods for suppressing flatworm gene function, using a technique called RNA interference (RNAi). They isolated and characterized the stem cells that underlie the flatworm's ability to regenerate, devised strategies for characterizing and sequencing thousands of relevant DNA sequences, and launched a large-scale effort to sequence the planarian's genome (or genetic composition).
A critical step forward in their quest occurred in 2005 when he and his team individually turned off 1,065 of the worm's genes, and found 240 that these genes were involved in some aspect of regeneration. Equally important, he found that 85 percent of these genes are found in the genomes of other organisms, including humans.
In explaining the planarian's remarkable capacity to regenerate, Alejandro says: "A fragment 1/279th the size of this original animal can regenerate a complete organism. I also consider planaria to be an excellent model to teach us a lot about how to monitor and regulate a population of stem cells [prevalent in the planarian regeneration] in vivo, rather than in a Petri dish."
A native of Venezuela, Alejandro arrived at Vanderbilt University in Nashville, TN as a young student where he excelled as an undergraduate. Graduating from Vanderbilt with a Bachelor's degree in Molecular Biology and Chemistry, he went on to the University of Cincinnati College of Medicine where he earned his Ph.D. in Pharmacology and Cell Biophysics.
He later served as a Post-Doctoral Fellow from 1994 to 1995, and as a Staff Associate from 1995 to 2001 at the Carnegie Institution of Washington, Department of Embryology.
In addition to his current investigative posts at Howard Hughes Medical Institute and Stowers Medical Institute, he has also served as Adjunct Professor of Neurobiology & Anatomy at the University of Utah School of Medicine, and is co-director of the Embryology Course at the Marine Biological Laboratory in Woods Hole, MA.
Alejandro is the recipient of numerous awards and honors for this research, including: the MERIT Award from the National Institutes of Health; being name a Kavli Fellow with the National Academy of Sciences, and receiving the E.E. Just Lecture Award from the American Society for Cell Biology.
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