(Press-News.org) ANN ARBOR--For decades, scientists have known that ET-743, a compound extracted from a marine invertebrate called a mangrove tunicate, can kill cancer cells. The drug has been approved for use in patients in Europe and is in clinical trials in the U.S.
Scientists suspected the mangrove tunicate, which is a type of a sea squirt, doesn't actually make ET-743. But the precise origins of the drug, which is also known as trabectedin, were a mystery.
By analyzing the genome of the tunicate along with the microbes that live inside it using advanced sequencing techniques, researchers at the University of Michigan were able to isolate the genetic blueprint of the ET-743's producer--which turns out to be a type of bacteria called Candidatus Endoecteinascidia frumentensis.
The findings greatly expand understanding of the microbe and of how ET-743 is produced, the researchers reported online May 27 in the journal Environmental Microbiology. They're optimistic that the insights will help make it possible to culture the bacteria in the laboratory without its host.
"These symbiotic microbes have long been thought to be the true sources of many of the natural products that have been isolated from invertebrates in the ocean and on the land. But very little is known about them because we're not able to get most of them to grow in a laboratory setting," said study senior author David Sherman, the Hans W. Vahlteich Professor of Medicinal Chemistry in the College of Pharmacy and a faculty member of the U-M Life Sciences Institute, where his lab is located.
"Currently, many of these compounds can only be harvested in small amounts from host animals, which is unsustainable from an economic and environmental perspective," said Michael Schofield, one of two first authors on the study and a member of the Sherman lab before she graduated from U-M this spring. "Our hope is that understanding the genomes of these micro-organisms and the chemical reactions that occur inside of them will provide new avenues to economical and sustainable production of the medicinal molecules they make."
ET-743 is currently made using a complicated, partially synthetic process.
"A major challenge of sequencing genomes from samples containing a mixture of different organisms is figuring out which DNA sequences go with which organisms. We used bioinformatic approaches that allowed us to tease that apart," said Sunit Jain, a bioinformatics specialist in the U-M Department of Earth and Environmental Sciences, and the study's other first author.
Bioinformatics involves the collection, classification, storage and analysis of biochemical and biological information using computers.
The University of Michigan has filed for patent protection on this discovery.
INFORMATION:
The research was supported by the International Cooperative Biodiversity Groups initiative at the Fogarty International Center, National Science Foundation and the U.S. Department of Energy's Joint Genome Institute. Additional authors include Daphne Porat, U-M Life Sciences Institute, and Gregory Dick, U-M Department of Earth and Environmental Sciences.
More information about the Sherman lab and efforts to discover drugs in the natural world can be found at myumi.ch/JyKR7.
WASHINGTON -- A national regulatory framework designed to prevent and limit indoor tanning is needed to alleviate the cancer burden and reduce the billions in financial costs from preventable skin cancer, say two Georgetown University public health experts.
In their "Viewpoint" published online today in JAMA, Darren Mays, PhD, MPH, and John Kraemer, JD, MPH, explore a regulatory opportunity--similar to the way toy safety standards were achieved--that could help drive strong, national policies regarding indoor tanning.
According to "The Surgeon General's Call to Action ...
Psychotic experiences were infrequent in the general population, with an average lifetime prevalence of ever having such an episode estimated at 5.8 percent, according to an article published online by JAMA Psychiatry.
Interest in the epidemiologic landscape of hallucinations and delusions has grown because these psychotic experiences (PEs) are reported by a sizable minority of the population. Some have called for more fine-grained analyses of PEs to guide the field.
Researcher John J. McGrath, Ph.D., M.D., of the University of Queensland, Australia, and coauthors examined ...
An Internet-based acne education program that included automated counseling was not better than a standard educational website in improving acne severity and quality of life in adolescents, according to an article published online by JAMA Dermatology.
Acne vulgaris is a chronic inflammatory skin disease that is prevalent among adolescents. Patient education is an important part of managing acne along with medication. However, the effect of patient education on clinical outcomes is not well characterized in dermatology publications.
Researcher April W. Armstrong, M.D., ...
The controversial practice of administering pre-surgery beta-blockers to patients having noncardiac surgery was associated with an increased risk of death in patients with no cardiac risk factors but it was beneficial for patients with three to four risk factors, according to a report published online by JAMA Surgery.
Pre-surgery β-blockade is a widely accepted practice in patients having cardiac surgery. But its use in patients at low risk of heart-related events having noncardiac surgery is controversial because of the increased risk of stroke and hypotension (low ...
SAN DIEGO, Calif. (May 27, 2015)-- In what may be the largest study ever conducted on changes in Americans' religious involvement, researchers led by San Diego State University psychology professor Jean M. Twenge found that millennials are the least religious generation of the last six decades, and possibly in the nation's history.
The researchers -- including Ramya Sastry from SDSU, Julie J. Exline and Joshua B. Grubbs from Case Western Reserve University and W. Keith Campbell from the University of Georgia -- analyzed data from 11.2 million respondents from four nationally ...
Seeking to advance minimally invasive medical treatments, researchers have proposed using tiny robots, driven by magnetic potential energy from magnetic resonance imaging (MRI) scanners.
The researchers described the work in a paper presented this week during ICRA, the conference of the IEEE Robotics and Automation Society in Seattle.
Aaron T. Becker, assistant professor of electrical and computer engineering at the University of Houston, said the potential technology could be used to treat hydrocephalus and other conditions, allowing surgeons to avoid current treatments ...
LOGAN, UT -- Fruit growers in the U.S. Intermountain West (the region including the states of Montana, Utah, Idaho, Wyoming, and Colorado) are faced with challenges that include decreased agricultural land availability, harsh climatic conditions, and significant competition from both domestic production and imports. In order to keep fruit production viable in the region, growers need to adopt strategies that minimize these challenges. The authors of a new report have identified production technologies that can extend the growing season for strawberry crops and result in ...
WASHINGTON (May 27, 2015) --George Washington University (GW) researcher Valerie Hu, Ph.D., has found an important sex-dependent difference in the level of RORA protein in brain tissues of males and females. Specifically, females without autism have a slightly higher level of RORA in the frontal cortex of the brain than males without autism, while the levels of the protein are comparably lower in the brain of both males and females with autism. The new study, published this month by Molecular Autism in a special issue on sex differences in autism, further shows a stronger ...
SHIRAZ, IRAN - Following the introduction of kiwifruit to the world market from New Zealand in the 1950s, increased export of kiwi led to rapid expansion in consumer demand and production. One of the challenges for growers is kiwifruit's short storage life; the popular fruit is susceptible to severe disorders during storage. A new study from Iran recommends treatments that can extend storage life and improve quality in kiwifruit.
Shirin Shahkoomahally and Asghar Ramezanian from the Department of Horticultural Science at Shiraz University published the study in the March ...
Women tolerate an unattractive man up to a point, but beware if he misbehaves. Then they'll easily shun him. So says Jeremy Gibson and Jonathan Gore of the Eastern Kentucky University in the U.S., after finding that a woman's view of a man is influenced by how handsome and law-abiding he is. Their study in Springer's journal Gender Issues has significance for those using dating sites or doing jury duty.
Discovering how someone can make a positive first impression is an important field of study, because of its role in forming relationships. It is often based on physical ...
