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Archive - Mar 29, 2017

Fred Hutch Scientists Will Cover Advances in Immunotherapy & Proteomics at AACR Annual Meeting

Scientists from the Fred Hutchinson Cancer Research Center in Seattle, Washington are scheduled to present and discuss the latest developments in immunotherapy and proteomics at the American Association for Cancer Research (AACR) Annual Meeting “Research Propelling Cancer Prevention and Cures” April 1-5 in Washington, D.C. What follows here is a selection of the more than 30 Hutch presentations scheduled to be given at the AACR gathering. Dr. Kristin Anderson, a postdoctoral fellow in Dr. Philip Greenberg's lab at Fred Hutch, will present findings on a new adoptive T-cell therapy for ovarian cancer, a type of solid tumor with a very low survival rate and few new treatment options. Dr. Anderson and her colleagues engineered T-cells to recognize a protein overproduced on these cancer cells, and then tested the therapy on human ovarian cancer cells in the lab and in a mouse model of ovarian cancer. The findings showed that the T-cells killed human ovarian cancer cells and that the treatment extended the mice's survival. But the research also highlighted how the tumor microenvironment of ovarian cancer presents unique challenges to the therapy. Dr. Anderson and her colleagues have identified several roadblocks to T-cell therapy that are unique to solid tumors (as compared with blood cancers, where T-cell therapy has progressed farther toward clinical benefit) and will present strategies underway in the Greenberg lab to overcome those roadblocks with new therapies. Dr. Anderson is speaking on April 4 at 3:50 p.m. Her talk is titled, "Engineering Adoptive T-Cell Therapy for Efficacy In Ovarian Cancer." From the Human Genome Project onward, we've made a massive investment in science aimed at understanding human genomics.

Social Bees Have Kept Their Gut Microbes for 80 Million Years

Approximately 80 million years ago, a group of bees began exhibiting social behavior, which includes raising young together, sharing food resources and defending their colony. Today, their descendants--honey bees, stingless bees, and bumble bees--carry stowaways from their ancient ancestors: five species of gut bacteria that have evolved along with the host bees. These bacteria, living in the guts of social bees, have been passed from generation to generation for 80 million years, according to a new study published in the March 29, 2017 issue of Science Advances and led by researchers at The University of Texas at Austin. The article is titled “Dynamic Microbiome Evolution in Social Bees.” The published finding adds to the argument that social creatures, like bees and humans, not only transfer bacteria among one another in their own lifetime--they have a distinctive relationship with bacteria over time, in some cases even evolving on parallel tracks as species. "The fact that these bacteria have been with the bees for so long says that they are a key part of the biology of social bees," says Nancy Moran, Ph.D., Professor of Integrative Biology at UT-Austin, who co-led the research with postdoctoral researcher Dr. Waldan Kwong. "And it suggests that disrupting the microbiome, through antibiotics or other kinds of stress, could cause health problems." Most insects, including nonsocial bees, do not have specialized gut microbes. Because they have limited physical contact with individuals of their own species, they tend to get their microbes from their environment. Social bees, on the other hand, spend much time in close contact with one another in the hive, making it easy to transfer gut microbes from individual to individual.

Simple Blood Test May Unlock New Frontier in Treating Depression; C-Reactive Protein Level Test Can Indicate Effective Antidepressant Medication for Individual Patient; "Can Immediately Be Used in Clinical Practice"

For the first time, doctors can determine which medication is more likely to help a patient overcome depression, according to research that pushes the medical field beyond what has essentially been a guessing game of prescribing antidepressants. A blood test that measures a certain type of protein level (level of C-reactive protein) provides an immediate tool for physicians who, until now, have relied heavily on patient questionnaires to choose a treatment, said Dr. Madhukar Trivedi, who led the research at the University of Texas (UT) Southwestern Medical Center's Center for Depression Research and Clinical Care. "Currently, our selection of depression medications is not any more superior than flipping a coin, and yet that is what we do. Now we have a biological explanation to guide treatment of depression," said Dr. Trivedi, Director of the Center for Depression Research and Clinical Care, a cornerstone of UT Southwestern's Peter O'Donnell Jr. Brain Institute. The study demonstrated that measuring a patient's C-reactive protein (CRP) levels through a simple finger-prick blood test can help doctors prescribe a medication that is more likely to work. Utilizing this test in clinical visits could lead to a significant boost in the success rate of depressed patients who commonly struggle to find effective treatments. A major national study (STAR*D) Dr. Trivedi led more than a decade ago gives insight into the prevalence of the problem: Up to a third of depressed patients don't improve during their first medication, and about 40 percent of people who start taking antidepressants stop taking them within three months. "This outcome happens because they give up," said Dr. Trivedi, whose previous national study established widely accepted treatment guidelines for depressed patients.

Japanese Researchers Illuminate Enzymatic Process That Produces Bilirubin, the Anti-Oxidant Molecule That, in Excess, Is Associated with Jaundice

Jaundice, marked by yellowing of the skin, is common in infants, but is also a symptom of various adult diseases. This discoloration is caused by excess bilirubin (BR), the substance that gives bile its yellow tinge. However, BR is also a vital antioxidant, which at healthy levels protects cells against peroxide damage. Its production in the body, though, has long been a source of uncertainty. Now, a Japanese research collaboration involving Osaka University and other Japan institutions believes it has the answer. BR is already known to be produced from a related chemical, biliverdin (BV), by the enzyme biliverdin reductase (BVR). The enzyme wraps around BV and transfers two hydrogen atoms – one positive and one negative – to produce the yellow antioxidant. However, biologists could not establish which part of the enzyme was chemically involved in the process (the active site), or where the positive hydrogen came from. The new findings, revealing this information, were published online on February 7, 2017 in Nature Communications. The open-access article is titled “A Substrate-Bound Structure of Cyanobacterial Biliverdin Reductase Identifies Stacked Substrates As Critical for Activity.” “Previous studies used BVR from rats, and could never crystallize the enzyme well enough to determine how it binds to BV,” study co-author Keiichi Fukuyama, Ph.D., says. “We realized that the same enzyme in Synechocystis bacteria had an almost identical fold-shape, but was easier to examine by X-ray crystallography.” To their surprise, the researchers found two molecules of BV – one stacked upon the other – at the active site, even though only one is converted to BR. From the X-ray data, they deduced why two were needed.

Viruses Use Special Proteins to Thwart Bacteria’s CRISPR Anti-Virus Defense System

For many bacteria, one line of defense against viral infection is a sophisticated RNA-guided “immune system” called CRISPR-Cas. At the center of this system is a surveillance complex that recognizes viral DNA and triggers its destruction. However, viruses can strike back and disable this surveillance complex using “anti-CRISPR” proteins, though no one has figured out exactly how these anti-CRISPRs work—until now. For the first time, researchers have solved the structure of viral anti-CRISPR proteins attached to a bacterial CRISPR surveillance complex, revealing precisely how viruses incapacitate the bacterial defense system. The research team, co-led by biologist Gabriel C. Lander, Ph.D., of The Scripps Research Institute (TSRI), discovered that anti-CRISPR proteins work by locking down CRISPR’s ability to identify and attack the viral genome. One anti-CRISPR protein even “mimics” DNA to throw the CRISPR-guided detection machine off its trail. “It’s amazing what these systems do to one-up each other,” said Dr. Lander. “It all comes back to this evolutionary arms race." The new research, co-led by Blake Wiedenheft, Ph.D., of Montana State University, was published in the March 23, 2017 issue of Cell. The article is titled “Structure Reveals Mechanisms of Viral Suppressors that Intercept a CRISPR RNA-Guided Surveillance Complex.” If CRISPR complexes sound familiar, that’s because they are at the forefront in a new wave of genome-editing technologies. CRISPR stands for “clustered regularly interspaced short palindromic repeats.” Scientists have discovered that they can take advantage of CRISPR’s natural ability to degrade sections of viral RNA and use CRISPR systems to remove unwanted genes from nearly any organism.