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Archive - Mar 9, 2017

Innovative Technique Greatly Increases Sensitivity of DNA Sequencing; New Molecular Barcode Technology Reduces Error Rate in Genomic Sequencing to 1 In 10,000

Ontario Institute for Cancer Research (OICR) researchers in Canada, together with international collaborators, have invented a technique to avoid a major problem with common laboratory techniques and improve the sensitivity of important cancer tests. The findings, published online on March 2, 2017 in Nature Protocols, describe a process by which the sensitivity of DNA sequencing can be improved. The technology, called SiMSen-Seq, could aid in detecting the recurrence of cancers, catching possible disease relapses faster than current methods and improving patient outcomes. The new article is titled “Simple Multiplexed PCR-Based Barcoding of DNA for Ultrasensitive Mutation Detection by Next-Generation Sequencing.” To sequence DNA, scientists often use a technique called polymerase chain reaction (PCR) to increase the amount of DNA available from a sample. However, PCR can introduce mistakes that can limit researchers' ability to detect real mutations in the original DNA molecules. To track the original molecules in a sample, molecular tags called DNA barcodes are added. This technique is essential for sensitive detection of mutations but can lead to other errors, as components of the tags can interfere with each other and affect the final results. "We created a DNA barcode with a hairpin structure that opens up to be read when heated and contracts when cooled. This allows us to 'hide' the barcode and analyze more patient DNA fragments in a single reaction," said Dr. Paul Krzyzanowski, Program Manager of OICR's Genome Technologies Program. Dr. Krzyzanowski led the development of the analysis pipeline software used in SiMSen-Seq. This software flags errors in sequencing results and corrects them computationally.

Tasmanian Devils Cured of Deadly Transmissible Cancer (DFTD) in Immunotherapy Trial

An international study involving multiple institutions over six years has shown that immunotherapy can cure Tasmanian devils of the deadly devil facial tumor disease (DFTD) (https://en.wikipedia.org/wiki/Devil_facial_tumour_disease), one of only two known naturally occurring transmissible cancers (the other being canine transmissible venereal tumor) (http://www.nature.com/onc/journal/v27/n2s/abs/onc2009350a.html). The new research was published in Scientific Reports. The open-access article is titled “Regression of Devil Facial Tumour Disease Following Immunotherapy in Immunised Tasmanian Devils.” The research was led by researchers from the University of Tasmania's Menzies Institute for Medical Research with input from scientists from the School of Medicine. It also involved researchers from the Walter and Eliza Hall Institute of Medical Research, CSL Ltd, and the Universities of Sydney, Southampton, Southern Denmark, and Cambridge. Professor Greg Woods, the leader of the DFTD team at Menzies, said scientists used immunotherapy on devils with golf-ball sized tumors and then observed the tumors gradually shrinking and disappearing over three months. "This is almost a Eureka moment for us because it's the first time we can say for sure that it was the immunotherapy that was making the tumor shrink," Professor Woods said. Building a good understanding of the devil's immune system, which goes hand in hand with the development of a vaccine, involves years of painstaking laboratory work. The process is incremental, but with each step, scientists are closing in on the disease. This breakthrough is the next step on from work published in 2015 that showed that the devil's immune system is capable of mounting an immune response to DFTD.

Mayo Clinic Researchers Identify Three New Agents (Senolytics) That May Delay Onset of Aging

Mayo Clinic researchers have identified three new agents to add to the emerging repertoire of drugs that are intended to delay the onset of aging by targeting senescent cells, i.e., cells that contribute to frailty and other age-related conditions. A recent study of human cell cultures shows that the drugs—the flavone fisetin and two BCL-XL inhibitors (A1331852 and A1155463)--cleared senescent cells in vitro. Findings were published online on March 8, 2017 in Aging. The open-access article is titled “New Agents That Target Senescent Cells: The Flavone, Fisetin, and The BCL-XL Inhibitors, A1331852 and A1155463.” "Senescent cells accumulate with age and at sites of multiple chronic conditions, such as in fat tissue in diabetes, the lungs in chronic pulmonary diseases, the aorta in vascular disease, or the joints in osteoarthritis," says James Kirkland, M.D., Ph.D., Director of the Mayo’s Robert and Arlene Kogod Center on Aging. "At Mayo Clinic, we discovered the first senolytic drugs - agents that selectively eliminate senescent cells while leaving normal cells unaffected. These senolytic agents alleviated a range of age- and disease-related problems in mice. We used the hypothesis-driven approach that we used to discover the first senolytic drugs, two published in early 2015 and another later in 2015, to discover these three new senolytic drugs." Mayo Clinic researchers, working in collaboration with the University Medical Center Groningen and The Scripps Research Institute, induced senescence in human cell cultures by radiating human primary preadipocytes, human umbilical vein endothelial cell cultures, and IMR90 cell cultures. Then, using an ATPLite and a crystal violet assay, researchers measured cell viability and demonstrated that fisetin and BCL-XL inhibitors A1331852 and A1155463 cleared senescent cells in vitro.

Stress-Induced Exosome Secretion Can Disrupt Communication Between Parasites That Spread Disease; New Intervention Approach May Lead to Development of Drugs to Treat and Prevent the Spread of Sleeping Sickness, Leshmaniasis, and Chagas Disease

Professor Shulamit Michaeli, Dean of Bar-Ilan's Mina and Everard Goodman Faculty of Life Sciences, and member of the Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA) in Israel, has demonstrated how parasite migration can be controlled by creating an unfavorable environment or by damaging cell health, because parasites under stress secrete vesicles (exosomes) that disrupt their socially coordinated movement in groups. This research was published online on March 3,2017 in PLOS Pathogens. The open-access article is titled “Exosome Secretion Affects Social Motility in Trypanosoma brucei.” Dr. Michaeli's team, including students Dror Eliaz and Sriram Kannan, study trypanosomatids, single-cell parasites that cause major diseases such as African sleeping sickness, leishmaniasis, and Chagas disease, affecting millions of people. Leishmaniasis, for example, is found in 88 countries and over 300 million people are at risk of infection. African trypanosomes infect cattle and the annual economic loss due to this disease is estimated at about US$2 billion. The American Chagas' disease causes major heart and intestinal malfunction. Approximately 90 million people are at risk of infection, with five to eight million people affected annually. Trypanosome parasites are transmitted to mammals by the blood-sucking tsetse fly. The parasites' stopover in the insect host has two stages. They live in the insect's gut for two to three weeks and then migrate to the saliva glands. When the fly has its next meal, the parasites are transferred via the saliva to the mammal prey, infecting the prey’s bloodstream. In this way, the mammal now becomes host to the parasite, and the disease is spread.

Stanford Biologists Identify Ancient Stress Response in Corals

Stanford marine biologists have discovered that corals activate a specific group of ancient, defensive genes when exposed to stressful environmental conditions. These stress-induced genes could serve as a kind of warning sign for coral bleaching events. In the study, researchers monitored three coral colonies in a lagoon on Ofu Island, American Samoa, for their response to stressors like high temperatures, oxygen, and ocean acidity. On the hottest days, the researchers saw a significant change in which genes the corals were activating within their cells. "They started using a whole set of genes that they had just not been using before," said Steve Palumbi, Ph.D., a Professor of Marine Sciences, Director of Hopkins Marine Station, and an author of the paper that outlines the study, published online on March 8, 2017 in Science Advances. The open-access article is titled “Tidal Heat Pulses on a Reef Trigger a Fine-Tuned Transcriptional Response in Corals to Maintain Homeostasis.” In 2016, the Great Barrier reef saw the worst coral bleaching event on record as corals across hundreds of miles turned stark white. These bleaching events can eventually lead to coral death. Scientists predict that global climate change and the continued increase in ocean temperatures will increase the frequency of coral bleaching worldwide. The tricky part is, corals don't show visible signs of bleaching beforehand. The genes identified in this study could give scientists a snapshot indication of coral health - and an idea of when bleaching is likely to occur. Under stressful conditions, a coral's normal cellular functions begin to fail. In response, the group of genes identified in this study triggers a process, called the unfolded protein response, that works to restore normal conditions within the cell.