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Archive - May 2017

Date

May 22nd

Day 3 of ISEV 2017 Annual Meeting in Toronto, Canada

Day 3 of the International Society for Extracellular Vesicles (ISEV) 2017 annual meeting in Toronto, Canada, opened with three simultaneous early-morning Meet the Experts sessions—one on “In Vivo Imaging-Based Analysis of EV-Biological Activity,” one on “Vesicular and Non-Vesicular Pathways of Extracellular RNA Release,” and the third on "EV-Mediated Parasite-Host Interactions.” These sessions are designed for experts to give brief opening talks and then to field questions from the audience. The third session was chaired by Dr. Ana Claudia Torrecilhas of the Federal University of Sao Paolo, and the featured expert speakers were Dr. Rodrigo Soares, of the Instituto Oswaldi Cruz in Brazil, who focused on the Trypanosoma cruzi parasite, and Dr. Martin Olivier, of McGill University in Canada, who spoke on Leishmania. Dr. Soares noted how T. cruzi EVs are agonists of the TLR2 receptor and stimulate the production of NO, TNF-, IL-6, and MAP kinases, eliciting a generally proinflammatory response that is conducive to the survival and invasiveness of the intracellular parasite. Dr. Olivier described how the Leismania parasite insect vector, the sand fly, transmits Leishmania EVs with its bite and that these EVs exacerbate Leishmania pathology. In addition, some of the Leishmania EVs contain a virus called LRV1. This virus can infect other Leishmania and exacerbate their virulence. The virus is not infective without the EV coat. Leishmania has a pro-inflammatory effect initially to attract vulnerable cells and then to sustain the infection. At the end of the session, Dr. Torrecilhas emphasized the need to better characterize the composition of parasite EVs to help better understand their immunomodulatory effects.

May 20th

Second Day of ISEV 2017 Annual Meeting in Toronto, Canada

The second day of the International Society for Extracellular Vesicles (ISEV) annual meeting began with three simultaneous early-morning Meet the Experts sessions—one on “EV-Mediated Functional Delivery of Protein and Nucleic Acids,” one on “EV lipids and Lipidomics,” and the third on “Rigor and Reproducibility in EV Analysis.” These sessions are designed for experts to give brief opening talks and then to field questions from the audience. The session on “EV-Mediated Functional Delivery of Protein and Nucleic Acids” was chaired by Lucia Languino and featured the expert speakers Janusz Rak from McGill University and Raghu Kalluri from the MD Anderson Cancer Center. Dr. Rak spoke first and emphasized that, despite the unequivocal functional consequences on target cells, an understanding of the uptake mechanisms and post-cargo processing for EVs remains elusive. He gave examples illustrating that proteins (TF and EGFR) could be transferred via EVs to recipient cells and shown to have activity. He noted the work of Jan Lötvall demonstrating the transfer of RNA via exosomes and he also cited recent evidence that ds genomic DNA could be transferred by EVs. Dr. Kalluri then came forward and focused on the question of how efficiently EV phenomena observed in vitro occurs in vivo. He said that these phenomena are likely highly regulated and happen at a relatively low efficiency in vivo or we wouldn’t be what we are. He said there must be in vivo barriers that exist that we are now unaware of and that it is important to understand how these barriers are overcome in some cases. He noted that there are likely different exosomes from different cells and perhaps different exosomes from cells in different states. There is a “booming” heterogeneity that needs to be unraveled, he said.

ISEV 2017 Conference Opens in Toronto, Canada

Day 1 of the Sixth Annual International Society for Extracellular Vesicles (ISEV) conference May 18-21 in Toronto, Canada, was officially opened Thursday morning with brief remarks by ISEV President Andy Hill, PhD, and International Organizing Committee Chairperson Sumitsa Sahoo, PhD. Dr. Hill welcomed the largest group of ISEV attendees ever (just slightly under 1,000) from more than 50 countries and applauded the worldwide research effort on EVs that is gathering ever-greater momentum. Dr. Sahoo warmly welcomed everyone to Canada and noted that the country is celebrating its 150th anniversary this year. She foreshadowed the seven plenary address that would be given over the next three days of the meeting and noted that 30 different symposia and six Meet the Expert sessions would be held in addition to many poster sessions and satellite events. She also thanked the numerous meeting sponsors. She then declared the meeting officially open and called on Marca Wauben, Ph.D., to introduce the first plenary speaker, Philip Stahl, PhD, the Edward Mallinckrodt Jr. Professor Emeritus, Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. But her introduction was extra-special as it began with her presenting Dr. Stahl with the prestigious ISEV 2017 Special Achievement Award for his work, in 1983, in first describing the “exosome secretion pathway” and demonstrating that multivesicular bodies (MVBs) release their vesicles into the extracellular milieu after fusion with the plasma membrane.Dr. Stahl’s research spans nearly five decades at Washington University in St. Louis. Initially focused on lysosomal enzymes and lysosome biogenesis, the Stahl Laboratory and its many students have made a number of seminal contributions to our understanding of endocytosis, membrane trafficking, and cell signaling.

May 19th

Education Day Sets Stage for ISEV 2017 Annual Meeting in Toronto

A highly stimulating and information-packed Education Day on extracellular vesicles (EVs) was held on Wednesday, May 17, in preparation for the four-day International Society for Extracellular Vesicles (ISEV) sixth annual meeting taking place this year in Toronto, Canada, May 18-21. The Education Day, sponsored by BioCytex (http://www.biocytex.com/) and attended by nearly 400 scientists from around the world, featured a full day of scientific presentations in two different tracks: Track A: EV Biology and Technology, and Track B: EVs in Health and Disease. Track A started out with warm welcoming remarks by International Organization Chair Susmita Sahoo, PhD, Assistant Professor of Medicine, Cardiology at the Icahn School of Medicine at Mount Sinai, who highlighted the comprehensive educational resource provided by the Massive Open Online Course (MOOC) that the ISEV offers. Then Clotilde Thery, PhD, opened the session with a talk on the “Rise of the Extracellular Vesicle Paradigm of Cellular Regulation.” Dr. Thery is an INSERM Director of Research at the Institut Pasteur in Paris. She performed and published the first proteomic studies of exosomes secreted by immune dendritic cells and since 2007 has been leading the “Exosomes and Tumor Growth” team at the Institut Curie. In her ISEV address, Dr. Thery first emphasized that the EV field today is quite similar to where the field of immunology was 50 years ago when researchers were just beginning to grapple with the heterogeneity of white blood cells. We need new tools to separate and distinguish different subpopulations of EVs, she suggested In her work, she has found that small EVs isolated by differential centrifugation and flotation density gradient separation that show simultaneous immune-isolation with anti-CD81, anti-CD63, and anti-CD9 can defined as exosomes.

May 15th

IBM Lab-on-a-Chip Nanochannel Technology Can "Stretch" DNA, Has Potential to Help Detect Disease

On May 15, 2017, IBM announced that its scientists have developed a "lab-on-a-chip" technology that can stretch double-stranded DNA molecules with the potential to efficiently reveal biomarkers that may indicate disease. This technology complements the IBM Research's "lab-on-a-chip" nanaDLD technology (https://www-03.ibm.com/press/us/en/pressrelease/50275.wss) which separates bioparticles, such as exosomes, which may also contain biomarkers for disease detection. The nanochannel technology, which uses an array of diamond-shaped micropillars to pre-stretch DNA from its coiled state, before being pushed through the chip's nanochannels, could allow medical professionals to detect the presence of genomic alterations in the DNA molecules. Scientists have discovered that certain genetic alterations, such as fusions of different parts of DNA, or an unusual amplification of the number of copies of certain genes, or a simple change in the DNA sequence can increase susceptibility to disease, or be the sign of a developing cancer. The challenge is detecting these alterations in DNA with affordable and easy-to-deploy technology. Today, medical labs can detect genomic alterations from patients' DNA samples, but it requires lengthy, expensive processing of DNA samples from a tissue biopsy or from blood. Using standard silicon chip technology may enable the detection of these DNA alterations to be compact, more cost-effective, and easier for mass production. IBM's goal is to integrate the fluidic chip with electronics that make it possible to transmit the data from the chip to datacenters for analysis. The long-term vision is that medical professionals could have a point-of-care device, packaged with the biochip, to conduct DNA testing that is then sent to the cloud for analysis.

May 14th

Japanese Scientists Isolate Gene Critical for Plant Health; Study Shows That Holliday Junction Resolvases Mediate Chloroplast Nucleoid Segregation

Proper DNA inheritance is essential for healthy cell growth and division. The same goes for the genetic material found in chloroplasts: the energy centers of all plant cells. Chloroplast genomes -- likely vestiges of ancestral bacteria -- are organized into DNA-protein complexes called nucleoids. While significant work has been done to understand the dynamics of DNA in the nuclei of plant cells, little is known about the dynamics of chloroplast nucleoids. Now Yusuke Kobayashi, PhD, and Yoshiki Nishimura, PhD, of Kyoto University, Osami Misumi, PhD, of Yamaguchi University, and other collaborators have isolated and characterized a protein in chloroplasts that is essential for proper nucleoid segregation. Their findings were published online on May 11, 2017 in Science. The article is titled "Holliday-Junction Resolvases Mediate Chloroplast Nucleoid Segregation.” "To understand the dynamics of chloroplast nucleoids, we focused on their behavior during chloroplast division in the green alga Chlamydomonas reinhardtii," explains Dr. Nishimura. "We screened about 6,000 specimens with random mutations in their DNA and then isolated the ones with defective nucleoid segregation." One of these mutants was found to have a defect in a gene the team calls moc1, for "monokaryotic chloroplast 1". The chloroplasts in this mutant possessed only a single nucleoid, and showed unequal segregation during chloroplast division. A homologous moc1 gene was then found in a land plant commonly used for research, Arabidopsis thaliana. When mutated, the researchers discovered that these organisms exhibit growth defects and abnormal nucleoid segregation.

New Lung “Organoids” Mimic Features of Full-Size Lung; Mini-Organs May Aid In Understanding, Treating Respiratory Diseases

New lung "organoids"--tiny 3-D structures that mimic features of a full-sized lung--have been created from human pluripotent stem cells by researchers at the Columbia University Medical Center (CUMC). The team used the organoids to generate models of human lung diseases in a lab dish, models that could be used to advance our understanding of a variety of respiratory diseases. A paper detailing the discovery was published online on April 24, 2017 in Nature Cell Biology. The article is titled “A Three-Dimensional Model of Human Lung Development and Disease from Pluripotent Stem Cells.” Organoids are 3-D structures containing multiple cell types that look and function like a full-sized organ. By reproducing an organ in a dish, researchers hope to develop better models of human diseases, and find new ways of testing drugs and regenerating damaged tissue. "Researchers have taken up the challenge of creating organoids to help us understand and treat a variety of diseases," said Hans-Willem Snoeck, PhD, Professor of Medicine (in Microbiology & Immunology) at CUMC and lead investigator of the study. "But we have been tested by our limited ability to create organoids that can replicate key features of human disease." The lung organoids created in Dr. Snoeck's lab are the first to include branching airway and alveolar structures, similar to those in human lungs. To demonstrate their functionality, the researchers showed that the organoids reacted in much the same way as a real lung does when infected with respiratory syncytial virus (RSV). Additional experiments revealed that the organoids also responded as a human lung would when carrying a gene mutation linked to pulmonary fibrosis. RSV is a major cause of lower respiratory tract infection in infants and has no vaccine or effective antiviral therapy.

Fittest Tasmanian Devils Are Most Likely to Be Infected with Transmissible Facial Tumor Disease

Research published online on May 10, 2017 in Ecology Letters, shows that Tasmanian devils that catch devil facial tumor disease (DFTD) have higher survival and reproductive rates prior to disease-induced death than individuals that do not become infected. The article is titled “Infection of the Fittest: Devil Facial Tumor Disease Has Greatest Effect on Individuals with Highest Reproductive Output.” Typically infectious diseases affect mostly older, younger, or less healthy individuals. However, a team of scientists from Australia and the US, led by Dr. Konstans Wells of Griffith's Environmental Futures Research Institute (EFRI), found that devils with higher fitness are at highest risk of infection and death from facial tumors. Dr. Wells said this was probably because of the disease's mode of transmission among socially dominant individuals. "It's an important finding, as it indicates that the fittest devils, which are the ones typically engaging in mating or aggressive behavior, are at highest risk to acquire tumors," he said. Devil facial tumor disease - a proliferating cell line that grows into deadly tumors - is among only a few known cases of transmissible cancer and is believed to be transmitted when devils bite each other. Ten years of intensive field surveys of devils collected by study authors Dr. Rodrigo Hamede and Associate Professor Menna Jones of the University of Tasmania, combined with a novel statistical modelling approach to assess infection dynamics and tumor growth, led to the findings. Senior author Professor Hamish McCallum, also from EFRI, said the findings contradicted conventional wisdom that infection of relatively weakened individuals was commonplace in the spread and persistence of diseases.

May 12th

Invasive Lung Cancer Cells Display Symbiosis of “Leader” and “Follower” Cells

When cancer cells split off from a tumor to seed deadly metastases, they are thought to travel as clusters or packs, a phenomenon known as collective invasion. The members of an invasive pack are not all alike, scientists at Winship Cancer Institute of Emory University have learned. Lung cancer cells making up an invasive pack have specialized roles as leaders and followers, which depend on each other for mobility and survival, the scientists reported online on May 12, 2017 in Nature Communications. The open-access article is titled “Image-Guided Genomics of Phenotypically Heterogeneous Populations Reveals Vascular Signaling During Symbiotic Collective Cancer Invasion.” The differences between leaders and followers -- and their interdependence -- could be keys for future treatments aimed at impairing or preventing cancer metastasis, says senior author Adam Marcus, PhD, Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute and Emory University School of Medicine. "We're finding that leader and follower cells have a symbiotic relationship and depend on each for survival and invasion," he says. "Because metastatic invasion is the deadliest aspect of cancer, our goal is to find agents that disrupt that symbiotic relationship." Dr. Marcus and former graduate student Jessica Konen, PhD, began by observing how a mass of lung cancer cells behaves when embedded in a 3-D protein gel. The cells generally stick together, but occasionally, a few cells extend out of the mass like tentacles, with the leader cell at the tip. "We saw that when the leader cell became detached or died unexpectedly, the followers could no longer move," says Dr. Konen, now a postdoctoral fellow at MD Anderson.

Single-Cell RNA Sequencing Used in Tracking Maturation of Olfactory Stem Cells

Adult stem cells have the ability to transform into many types of cells, but tracing the path individual stem cells follow as they mature and identifying the molecules that trigger these fateful decisions are difficult in a living animal. University of California, Berkeley, neuroscientists have now combined new techniques for sequencing the RNA in single cells with detailed statistical analysis to more easily track individual stem cells in the nose, uncovering clues that someday could help restore smell to those who have lost it. The results are published this week in the journal Cell Stem Cell. The article is titled “Deconstructing Olfactory Stem Cell Trajectories at Single-Cell Resolution.” "A stem cell's job is twofold: to replace or recreate mature cells that are lost over time, both through normal aging and after injury, and to replace themselves so that the process can continue over the life of the animal," said senior author John Ngai, PhD, the Coates Family Professor of Neuroscience and a member of UC Berkeley's Helen Wills Neuroscience Institute and the Berkeley Stem Cell Center. "We are getting closer to understanding how mature sensory neurons are generated from olfactory stem cells, an understanding that's key for an eventual stem cell therapy to restore function." Dr. Ngai noted that perhaps one-quarter of all people over the age of 50 have some loss of smell, yet doctors have little understanding why, and no treatments for most cases. There's not even a standardized test for loss of smell, as there is for vision or hearing loss, in spite of widespread reports of suffering by patients who have lost their sense of smell. "Some cases of anosmia -- the loss of the sense of smell -- are due to traumatic injury, and there is generally not a whole lot you can do about that," he said.