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Archive - Sep 27, 2015

Ultra-Stability of Heme-Free Myoglobin in Deep-Diving Whales Is Clue to Engineering Bacteria That Can Produce Abundant Hemoglobin for Use in Synthetic Human Blood Substitutes

The ultra-stable properties of the proteins that allow deep-diving whales to remain active while holding their breath for up to two hours could help Rice University biochemist Dr. John Olson and his colleagues finish a 20-year quest to create lifesaving synthetic blood for human trauma patients. In a new study featured as one of two papers of the week in the September 25, 2015 issue of the Journal of Biological Chemistry, Dr. Olson and colleagues Dr. George Phillips, Dr. Lucian Smith, and Premila Samuel compared the muscle protein myoglobin from humans, whales, and other deep-diving mammals. The article is titled "Apoglobin Stability Is the Major Factor Governing Both Cell-Free and In Vivo Expression of Holomyoglobin." Myoglobin holds oxygen for ready use inside muscle cells, and the study found that marine mammals have ultra-stable versions of myoglobin that tend not to unfold. The researchers found that stability was the key for cells to make large amounts of myoglobin, which is explains why deep-diving mammals can load their muscle cells with far more myoglobin than humans. "Whales and other deep-diving marine mammals can pack 10-20 times more myoglobin into their cells than humans can, and that allows them to 'download' oxygen directly into their skeletal muscles and stay active even when they are holding their breath," said Dr. Olson, Rice's Ralph and Dorothy Looney Professor of Biochemistry and Cell Biology. "The reason whale meat is so dark is that it's filled with myoglobin that is capable of holding oxygen. But when the myoglobin is newly made, it does not yet contain heme. We found that the stability of heme-free myoglobin is the key factor that allows cells to produce high amounts of myoglobin." This finding is important to Dr.

Viruses May Be Alive; Protein Fold Study Supports This Hypothesis; Data Suggests Viruses Evolved from Ancient Cells with Segmented RNA Genomes

A new analysis supports the hypothesis that viruses are living entities that share a long evolutionary history with cells, researchers report. The study offers the first reliable method for tracing viral evolution back to a time when neither viruses nor cells existed in the forms recognized today, the researchers say. The new findings were published online on September 25, 2015 in an open-access article in the journal Science Advances. The article is titled “"A Phylogenomic Data-Driven Exploration of Viral Origins and Evolution.” Until now, viruses have been difficult to classify, said University of Illinois at Urbana-Champaign Crop Sciences and Carl R. Woese Institute for Genomic Biology Professor Gustavo Caetano-Anollés, Ph.D., who led the new analysis with graduate student Arshan Nasir. In its latest report, the International Committee on the Taxonomy of Viruses recognized seven orders of viruses, based on their shapes and sizes, genetic structure, and methods of reproducing. "Under this classification, viral families belonging to the same order have likely diverged from a common ancestral virus," the University of Illinois authors wrote. "However, only 26 (of 104) viral families have been assigned to an order, and the evolutionary relationships of most of them remain unclear." Part of the confusion stems from the abundance and diversity of viruses. Fewer than 4,900 viruses have been identified and sequenced so far, even though scientists estimate there are more than a million viral species. Many viruses are tiny - significantly smaller than bacteria or other microbes - and contain only a handful of genes. Others, like the recently discovered mimiviruses, are huge, with genomes larger than those of some bacteria.

“Matchmaker Exchange” Launched to Aid Rare Genetic Disease Community; New Platform Harnesses Data from Multiple Databases to Simplify Searches for Causes of Rare Genetic Diseases

In the October 2015 issue of Human Mutation, a team of geneticists, including investigators at Brigham and Women's Hospital (BWH), has announced the launch of the Matchmaker Exchange - a platform that the rare genetic disease community can use to share information and find new connections. The Matchmaker Exchange platform connects databases of genetic information and symptoms that physicians and investigators can "match" with a patient's rare disease." In the past, searching for the cause of a rare genetic disease was like trying to find a needle in a haystack. There would be an occasional, serendipitous connection made by a clinical laboratory or individual investigator of two patients who shared the same rare disease, but there was no systematic way to find these matching cases," said Heidi Rehm, Ph.D., a molecular geneticist at BWH and Director of the Laboratory for Molecular Medicine at Partners HealthCare Personalized Medicine. "Matchmaker Exchange offers a reliable, scalable way to find matching cases and identify their genetic causes." The Human Mutation article is titled “The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery." Matchmaker Exchange (MME) 1.0 brings together multiple databases and programs and harnesses collective data from across rare disease repositories. The platform allows investigators to search the databases and uncover similar symptoms and genetic profiles, using standardized application programming interfaces (APIs) and procedural conventions. Using a federated network approach, MME protects the privacy and security of patient data while connecting the databases through APIs.

Brain Metastases Have Different Genetic Mutations Than the Primary Tumor; Many May Be Targetable with Existing Chemotherapy; International Study Suggests Routinely Looking for These Mutations May Benefit Patients

The development of brain metastases is a devastating complication of cancer, leading to the death of more than half of patients whose cancer spreads to the brain. A new study finds that, while brain metastases share some genetic characteristics with the primary tumors from which they originated, they also carry unique genetic mutations, indicating that the evolutionary pathways of the metastatic and the primary tumors have diverged, which may change sensitivities to targeted therapy drugs. The report from an international collaboration was published online on September 26, 2015 in Cancer Discovery to coincide with a presentation at the European Cancer Congress and European Society for Medical Oncology meeting in Vienna, Austria. "Our study demonstrates that, while brain metastases and primary tumors share a common ancestry, they continue to evolve separately," says Priscilla Brastianos (photo), M.D., Director of the Brain Metastasis Program at the Massachusetts General Hospital (MGH) Cancer Center, co-lead and co-corresponding author of the Cancer Discovery paper. "This is tremendously important, as we demonstrate that brain metastases may have clinically significant mutations that have not been detected either in the primary tumor biopsy or in metastases from other parts of the body. We also showed that multiple brain metastases from the same patient share nearly all clinically significant mutations." The Cancer Discovery article is titled “Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets.” Brain metastases commonly develop from melanomas, lung, or breast cancers and can appear despite the primary tumor's being well controlled by drugs that target mutations driving its growth.