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News Article | May 9, 2017
Site: www.eurekalert.org

LA JOLLA, CA - May 9, 2017 - Three chemists from The Scripps Research Institute (TSRI)--Dale Boger, Jin-Quan Yu and Phil Baran--have received awards from the Royal Society of Chemistry (RSC), a renowned professional organization for chemists based in the United Kingdom, with more than 54,000 members worldwide. Dale Boger, co-chair of the Department of Chemistry at TSRI, was awarded the 2017 Robert Robinson Award of the RSC's Organic Division. The award honors his groundbreaking studies in natural product synthesis, which could lead to new therapeutic treatments for challenging clinical needs. "I am very honored and humbled to receive the RSC Robert Robinson Award, which has such a distinguished list of prior award winners," Boger said. Jin-Quan Yu, Frank and Bertha Hupp Professor of Chemistry at TSRI, received the 2017 Pedler Award from the RSC's Organic Division in recognition of his development of pioneering methods of C-H activation, a technique in chemistry that can lead to new pharmaceuticals and other natural products. "I hope these new reactions will accelerate the discovery and synthesis of useful molecules, especially medicines," said Yu, who received his Ph.D. in the U.K. at the University of Cambridge and served as a Royal Society fellow. "It gives me a warm feeling to be recognized by the U.K. scientific community that I was part of for 10 years." Phil Baran, the Darlene Shiley Professor of Chemistry at TSRI, received the RSC's 2017 Merck, Sharp & Dohme Award, which honors contributions to any area of organic chemistry from a researcher under the age of 45. Baran's work focuses on developing new chemical reactions and methodologies for more efficient and economically viable routes in drug design. Baran credited his lab members for his success so far. "This award is a recognition of the students and postdoctoral scholars who work tirelessly to invent useful chemistry," Baran said. In addition to £2,000 and a medal, all three awards include a lecture tour in the U.K. The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists -- including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine -- work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www. .


News Article | May 11, 2017
Site: www.eurekalert.org

LA JOLLA, CA - May 11, 2017 - In their quest to replicate themselves, viruses have gotten awfully good at tricking human cells into pumping out viral proteins. That's why scientists have been working to use viruses as forces for good: to deliver useful genes to human cells and help patients who lack important proteins or enzymes. A team of researchers led by Associate Professor Vijay Reddy at The Scripps Research Institute (TSRI) has now uncovered the structural details that make one virus a better tool for future therapies than its closely related "cousin." As Reddy and his colleagues reported this week in the journal Science Advances, the structure of a less prevalent species D adenovirus may work well as a gene-delivery vector because its structure doesn't let it get spirited away to the liver, minimizing liver toxicity. The Reddy Lab's study is the first to show the structural details on species D's surface that set it apart from another common subtype of adenovirus, called species C, which does travel to the liver. "Greater understanding of the structures of adenoviruses from different species will help generate better gene therapies and/or vaccine vectors," said Reddy. Using an imaging technique called cryo-electron microscopy, the researchers discovered that while these two species of adenoviruses share the same shell-like core, they have different surface structures, which Reddy called "decorations" or "loops." These loops are key to a virus's behavior. They determine which receptors on human cells the virus can bind to. For species C adenoviruses, specific loops help the virus attach to blood coagulation factors (adaptor proteins) and get targeted to the human liver. Species D adenoviruses display distinctly different loop decorations. For use in gene and vaccine therapies, the virus would deliver helpful genes instead. Plus, species D has one more important advantage over species C: Humans are constantly exposed to species C adenoviruses, so most people have developed antibodies to fight them off. These same antibodies would fight off the species C viruses even if they were designed for beneficial therapies. On the flip side, many of the species D adenoviruses are rare, and it's unlikely that a patient would have antibodies to fight them off. That makes species D viruses better for delivering therapies. In fact, Reddy said scientists are already testing ways to use it to generate malaria and Ebola virus vaccines. The researchers next plan to look at members of the other five species of adenoviruses to see if they would have useful traits as viral therapy vectors. In addition to Reddy, the first authors of the study, "Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses," were Xiaodi Yu and David Veesler, formerly at TSRI, now at Pfizer Worldwide R&D, and the University of Washington, Seattle, respectively. Additional authors were Melody Campbell, formerly at TSRI, now at the University of California, San Francisco; Mary E. Barry and Michael A. Barry of the Mayo Clinic; and Francisco Asturias of TSRI. Reddy also thanked Bridget Carragher and Clint Potter, directors of the National Resource for Automated Molecular Microscopy (NRAMM) facility for their support and collaboration. The study was supported by the National Institutes of Health (grants R01AI070771, R21AI103692 and GM103310). The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists--including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine--work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www. .


A team of researchers led by Associate Professor Vijay Reddy at The Scripps Research Institute (TSRI) has now uncovered the structural details that make one virus a better tool for future therapies than its closely related "cousin." As Reddy and his colleagues reported this week in the journal Science Advances, the structure of a less prevalent species D adenovirus may work well as a gene-delivery vector because its structure doesn't let it get spirited away to the liver, minimizing liver toxicity. The Reddy Lab's study is the first to show the structural details on species D's surface that set it apart from another common subtype of adenovirus, called species C, which does travel to the liver. "Greater understanding of the structures of adenoviruses from different species will help generate better gene therapies and/or vaccine vectors," said Reddy. Using an imaging technique called cryo-electron microscopy, the researchers discovered that while these two species of adenoviruses share the same shell-like core, they have different surface structures, which Reddy called "decorations" or "loops." These loops are key to a virus's behavior. They determine which receptors on human cells the virus can bind to. For species C adenoviruses, specific loops help the virus attach to blood coagulation factors (adaptor proteins) and get targeted to the human liver. Species D adenoviruses display distinctly different loop decorations. For use in gene and vaccine therapies, the virus would deliver helpful genes instead. Plus, species D has one more important advantage over species C: Humans are constantly exposed to species C adenoviruses, so most people have developed antibodies to fight them off. These same antibodies would fight off the species C viruses even if they were designed for beneficial therapies. On the flip side, many of the species D adenoviruses are rare, and it's unlikely that a patient would have antibodies to fight them off. That makes species D viruses better for delivering therapies. In fact, Reddy said scientists are already testing ways to use it to generate malaria and Ebola virus vaccines. The researchers next plan to look at members of the other five species of adenoviruses to see if they would have useful traits as viral therapy vectors. Explore further: Adenoviruses may pose risk for monkey-to-human leap More information: Xiaodi Yu et al, Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses, Science Advances (2017). DOI: 10.1126/sciadv.1602670


LA JOLLA, CA - February 22, 2017 - The MagnaSafe Registry, a new multicenter study led by scientists at The Scripps Research Institute (TSRI), has demonstrated that appropriately screened and monitored patients with standard or non-MRI-conditional pacemakers and defibrillators can undergo MRI at a field strength of 1.5 tesla without harm. These devices are not presently approved by the U.S. Food and Drug Administration (FDA) for MRI scanning. The researchers observed no patient deaths, device or lead failures, losses of pacing function or ventricular arrhythmias in 1,500 patients who underwent MRI using a specific protocol for device interrogation, device programming, patient monitoring and follow-up designed to reduce the risk of patient harm from MRI effects. The research will be published as an Original Article in the February 23, 2017 issue of The New England Journal of Medicine. The use of MRI poses potential safety concerns for patients with an implanted cardiac device. These concerns are a result of the potential for magnetic field-induced cardiac lead heating, which could result in cardiac injury and damage to an implanted device. As a result, it has long been recommended that patients with a pacemaker or defibrillator not undergo MRI scanning, even when MRIs are considered the most appropriate diagnostic imaging method for their care. Despite the development of devices designed to reduce the potential risks associated with MRI, a large number of patients have devices that have not been shown to meet these criteria and are considered "non-MRI-conditional." At least half these patients are predicted to have the need for MRI after a device has been implanted. Researchers established the MagnaSafe Registry to determine the frequency of cardiac device-related events among patients with non-MRI-conditional devices, as well as to define a simplified protocol for screening, monitoring and device programming before MRI. "Given the great clinical demand for MRI for patients with a standard pacemaker or defibrillator, we wanted to determine the risk," said study leader Dr. Robert Russo, an adjunct professor at TSRI and director of The La Jolla Cardiovascular Research Institute. In the MagnaSafe Registry, researchers at 19 U.S. institutions tested 1,000 cases with a non-MRI-conditional pacemaker (one not approved for use in an MRI) and 500 cases of patients with a non-MRI-conditional implantable cardioverter defibrillator (ICD), a device that can shock the heart in response to a potentially fatal cardiac rhythm. They scanned regions other than the chest, such as the brain, spine or extremities--where MRI is traditionally the best option for imaging. The researchers tested the devices at an MRI field strength of 1.5 tesla, a standard strength for MRI scanners and reprogrammed some devices according to a prespecified protocol for the MRI examination. "If the patient was not dependent upon their pacemaker, the device was turned off," explained Russo. "If they could not tolerate having the device turned off, it was set to a pacing mode that did not sense cardiac activity. The reason was that the pacemaker could sense the electrical activity (radiofrequency energy) from the MRI scanner and the function of the device could be inhibited, which could be catastrophic if you depend upon your pacemaker for your heartbeat." Russo and his co-investigators did observe adverse effects in a small group of patients. Six patients had a brief period of atrial fibrillation, and in six additional cases pacemaker partial reset (a loss of stored patient information) was noted. But in no cases did the researchers observe device failure or a failure in the leads that connect the device to the heart when the protocol was followed. "One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI," explained Russo. These findings led the researchers to conclude that "device removal and replacement seem unlikely to be safer than proceeding with scanning for patients with a pacemaker or an ICD who require a nonthoracic MRI," provided a protocol similar to the MagnaSafe protocol was followed. "Patients with a standard or non-MRI-conditional pacemaker can undergo clinically indicated MRI without harm if a protocol such as the 'MagnaSafe' protocol used in this study is followed and patients are screened and monitored as described," said Russo. The researchers also noted that their results may not be predictive of findings with all device and lead combinations, higher MRI field strengths, patients younger than 18 years of age and MRI examinations of the chest or cardiac resynchronization devices (those designed to increase the function of a failing heart). The researchers plan to follow up by studying the risk for patients in need of a chest scan at scanner field strength of 1.5 tesla, as well as an MRI of any anatomic area at a higher field strength (3.0 tesla). The study, "Assessing the Risks Associated with MRI in Patients with a Pacemaker or Defibrillator," also included authors from the University of California, San Diego; Scripps Memorial Hospital; the University of California, Los Angeles; Providence St. Joseph Medical Center; the University of Arizona; Intermountain Medical Center; Inova Heart and Vascular Institute; Allegheny General Hospital; Abington Memorial Hospital; Yale University School of Medicine; Providence Heart Institute; Oklahoma Heart Institute; the University of Mississippi Medical Center; the Medical College of Wisconsin; Bassett Medical Center; Carnegie Hill Radiology; Methodist DeBakey Heart and Vascular Center and Baptist Health. The study was supported by grants from St. Jude Medical, Biotronik, Boston Scientific and the Hewitt Foundation for Medical Research, and by philanthropic gifts from Mr. and Mrs. Richard H. Deihl, Evelyn F. and Louis S. Grubb, Roscoe E. Hazard, Jr. and the Shultz Steel Company. The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists--including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine--work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www. .


News Article | February 23, 2017
Site: www.eurekalert.org

ROCHESTER, Minn. -- A Mayo Clinic study has shown evidence linking the biology of aging with idiopathic pulmonary fibrosis, a disease that impairs lung function and causes shortness of breath, fatigue, declining quality of life, and, ultimately, death. Researchers believe that these findings, which appear today in Nature Communications, are the next step toward a possible therapy for individuals suffering from idiopathic pulmonary fibrosis. "Idiopathic pulmonary fibrosis is a poorly understood disease, and its effects are devastating," says Nathan LeBrasseur, Ph.D., director, Healthy Aging and Independent Living program, Mayo Clinic Robert and Arlene Kogod Center on Aging and senior author of this study. "Individuals with idiopathic pulmonary fibrosis express difficulty completing routine activities. There are currently no effective treatment options, and the disease leads to a dramatic decrease in health span and life span, with life expectancy after diagnosis between three to five years." Dr. LeBrasseur and his team, which included experts across several departments at Mayo Clinic, as well as Newcastle University Institute for Ageing and The Scripps Research Institute, studied the lung tissue of healthy individuals and of persons with mild, moderate and severe idiopathic pulmonary fibrosis. The tissue samples were made available from the Lung Tissue Research Consortium, a resource program of the National Heart, Lung, and Blood Institute, part of the National Institutes of Health (NIH). Researchers found that the markers of cellular senescence, a process triggered by damage to cells and linked to aging, were higher in individuals with idiopathic pulmonary fibrosis, and senescent cell burden increased with the progression of the disease. Then, they demonstrated that factors secreted by senescent cells could drive inflammation and aberrant tissue remodeling and fibrosis, which are hallmarks of idiopathic pulmonary fibrosis. "We discovered that senescent cells, which accumulate in the idiopathic pulmonary fibrosis lung, are a viable source of multiple factors that drive fibrotic activation," explains Marissa Schafer, Ph.D., a postdoctoral fellow in Dr. LeBrasseur's lab and lead author of the study. According to Dr. LeBrasseur, the findings represent a conceptual shift in the way they think about idiopathic pulmonary fibrosis. "Up to this point, research efforts have largely focused on understanding the unique elements that contribute to idiopathic pulmonary fibrosis. Here, we are considering whether the biology of aging is accelerated in this aggressive disease. What we've found is that senescent cells are prevalent, secreting toxic molecules that affect healthy cells in that environment and are essentially promoting tissue fibrosis." Equipped with the findings from their studies of human lung tissue, researchers then replicated the process in mice. They found that, much like in humans, mice with clinical features of idiopathic pulmonary fibrosis also demonstrated increased amounts of senescent cells. Researchers used a genetic model programmed to make senescent cells self-destruct and a drug combination of dasatinib and quercetin which, in previous studies conducted by Mayo Clinic, was shown to eliminate senescent cells. Results showed that clearing senescent cells from unhealthy mice improved measures of lung function and physical health, such as exercise capacity on a treadmill. While further research is needed, Drs. LeBrasseur and Schafer hope that targeting senescent cells could be a viable treatment option for individuals who suffer from idiopathic pulmonary fibrosis. "Previous work from the Center on Aging has shown in a number of models how senescent cells contribute to aging and aging-related conditions," says Dr. LeBrasseur. "We are exploring whether senolytic drugs, or drugs that can selectively kill senescent cells, can be used for the treatment of aging-associated conditions, including idiopathic pulmonary fibrosis. More research is needed to validate this, and our goal is to move quickly from discovery to translation to application, and, ultimately, meet the unmet needs of our patients." The research was supported by a Team Science Award from the Mayo Clinic Clinical and Translational Science Award grant from the National Center for Advancing Translational Science, National Institutes of Health, a generous gift from the John E. and Virginia H. Kunkel Family, the Glenn Foundation for Medical Research, the American Federation for Aging Research, the Connor Group, Noaber Foundation, the Mayo Clinic Robert and Arlene Kogod Center on Aging, a David Phillips Fellowship funded by the Biotechnology and Biological Sciences Research Council and a Biotechnology and Biological Sciences Research Council grant. Others on the research team are: Mayo Clinic and Drs. Kirkland, Pirtskhalava, Tchkonia and Zhu have a financial interest related to this research. Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. For more information, visit http://www. or http://newsnetwork. .


JUPITER, FL, Feb. 14, 2017 - A pair of scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded up to $3.3 million from the National Cancer Institute of the National Institutes of Health (NIH) to create the next generation of breast cancer treatments for the thousands of patients whose current treatment options are limited. Ben Shen, TSRI professor and co-chair of the Department of Chemistry, and Christoph Rader, TSRI associate professor in the Department of Immunology and Microbiology, will co-lead the new five-year study. The researchers aim to develop a potent type of therapy known as an antibody-drug conjugate (ADC). This new class of anti-cancer drugs combines the specificity of antibodies, which attack only cells they recognize, with a highly toxic payload designed to kill specific cancer cells with far greater efficiency than most currently available treatments. So far, only three of these combination therapies have been approved by the U.S. Food and Drug Administration (FDA). The new ADC approach targets HER2-postive and ROR1-positive breast cancers, which are often aggressive and harder to treat with conventional chemotherapy and hormone drugs. The new grant builds on the work done in both the Shen and Rader labs. Shen and his colleagues recently uncovered a new class of natural products called tiancimycins, (TNMs) which kill selected cancer cells more rapidly and more completely compared with the toxic molecules already used in FDA-approved ADCs. Rader, who has spent most of his scientific career at TSRI and the NIH, has been studying and developing site-specific ADCs to treat cancer. "This grant matches my lab's work on advancing antibody engineering and conjugation technologies with the world-class natural product-based drug discovery in Ben Shen's lab," Rader said. "It's precisely what I came to Scripps Florida for: to build new molecules at the interface of chemistry and biology that can advance medicine. I'm very pleased that the NIH continues to invest in our ideas." Since HER2 and ROR1 expression is highly complementary, the new collaboration could provide new treatment options for at least 50 percent of breast cancer patients, Shen noted. "At Scripps Florida we not only do great science, but we have even greater opportunities to collaborate on projects like this," Shen added. "The combination of Christoph Rader's antibody technology and the tiancimycins, which have been proven to be exquisitely potent, should produce an antibody drug conjugate that we hope to move very quickly into the clinic." The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists--including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine--work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www. .


News Article | February 15, 2017
Site: www.eurekalert.org

JUPITER, FL - February 15, 2017 - Scientists are working to understand the mechanisms that make weight loss so complicated. Exercise burns calories, of course, but scientists are also looking at how the body burns more energy to stay warm in cold temperatures. Is there a way to get metabolism to ramp up--even when it's not cold out? TSRI Assistant Professor Anutosh Chakraborty is on a mission to answer this question. His past research revealed a new therapeutic target in this battle--a protein that actually promotes fat accumulation in animal models by slowing stored energy (fat) breakdown and encouraging weight gain. Now, in a study recently published online in the journal Molecular Metabolism, Chakraborty and his colleagues have shown that deleting the gene for this protein, known as IP6K1, protects animal models from both obesity and diabetes. This protective effect is seen regardless of diet, even at what's known as a thermoneutral temperature (around 86?F). This means inhibiting IP6K1 should help animals burn more energy, regardless of outside conditions. "In genetically altered animal models that lack IP6K1, we found that deletion dramatically protects these knock-out mice from diet-induced obesity and insulin resistance regardless of the temperature in the environment," Chakraborty said. "When we inhibited the enzyme with chemical compounds, the results were similar." Temperature is important in the study of obesity because an animal in lower temperatures will rapidly lose weight as it burns more energy to try to maintain core body temperature. Because humans can maintain their body temperatures in a number of ways--clothing, for example--any pathway that reduces body weight at higher temperatures is a highly encouraging target in human obesity. The new study suggests a future pharmaceutical may be able to target IP6K1 to mimic the energy burning seen at relatively lower temperatures. "If we delete IP6K1, the animals gain less body weight because they simply expend more energy--regardless of temperature. That's important because blocking weight gain by enhancing energy expenditure in a thermoneutral environment is harder and thus, targeting IP6K1 is expected to be successful in ameliorating obesity in humans," said Chakraborty. "If you're developing an anti-obesity drug based on inhibiting IP6K1, our new findings shows that there are potentially very few restrictions for its use--a subject would lose weight even on a high-fat diet, and nobody would have to sit in a refrigerator to make it work," he added. The first author of the study, "Global IP6K1 deletion enhances temperature modulated energy expenditure which reduces carbohydrate and fat induced weight gain," is TSRI's Qingzhang Zhu. Other authors are Sarbani Ghoshal, at TSRI at the time of the study, now at the Saint Louis University School of Medicine, and Richa Tyagi of the Johns Hopkins University School of Medicine. This work is supported by the National Institutes of Health (grant R01DK103746) and the state of Florida. The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists--including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine--work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www. .


News Article | January 28, 2017
Site: www.techtimes.com

Researchers from The Scripps Research Institute have pinpointed a specific hormone in the brain that appears to be responsible for triggering fat burn in the gut. Serotonin has been established before as a driving factor for fat loss. However, it wasn't clear how exactly the neurotransmitter was able to influence fat reduction. To find out, Supriya Srinivasan and colleagues carried out experiments on Caenorhabditis elegans. Commonly used as a model organism in biological applications, the roundworm has a simpler metabolic system than people but features a brain capable of producing a lot of the same signaling molecules that a human brain does. As such, many researchers believe that results involving C. elegans may have potential relevance to humans. For a study published in the journal Nature Communications, the researchers erased certain genes in C. elegans to determine if it was possible to disrupt the path between serotonin in the brain and fat burning. Testing genes one after the other, they were able to zero in on a gene that codes for FLP-7, a neuropeptide hormone. According to the researchers, FLP-7 was actually identified as a muscle contraction-triggering peptide when applied to pig intestines. Back then, it was believed that the hormone connected the brain to the gut but it was not specifically linked to fat metabolism. After identifying FLP-7 as a fat-burning trigger, the researchers moved on to determining if it has a direct connection to levels of serotonin in the brain. Lavinia Palamiuc, the study's first author, led this part of the study by tagging FLP-7 using fluorescent red protein, allowing for the peptide to be viewed within C. elegans. Based on their observation, the researchers saw that FLP-7 was released by brain neurons responding to elevated levels of serotonin. The neuropeptide hormone then entered the circulatory system and started the fat-burning process within the gut. "That was a big moment for us," said Srinivasan. And understandably so, as this is the first time that researchers discovered a brain hormone that selectively and particularly spurs the fat-burning process without affecting food intake. While increasing levels of serotonin have a massive effect on food intake, reproductive behavior, and movement, increasing levels of FLP-7 did not have any obvious side effects, noted the researchers. Based on observations, the researchers simply continued functioning as usual while burning more fat. According to Srinivasan, this finding may encourage studies in the future to focus on how levels of FLP-7 can be regulated without resulting in side effects typically experienced when levels of serotonin are manipulated. Supported by grants from the NIH's Office of Research Infrastructure Programs and National Institute of Diabetes and Digestive and Kidney Diseases, the current study also included work from Tallie Noble, Megan Vaughan, Emily Witham, and Harkaranveer Ratanpal. For those interested in losing body fat, another study offers another tip: what time you eat your dinner may have a hand in how you burn off fat. According to the study, consuming meals within a smaller time frame in a day may boost weight loss abilities by increasing the body's capacity to consume proteins and burn fat. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


February 21, 2017 - Results from a new Phase 3 study conducted by the Celgene Corporation demonstrate that ozanimod, a drug candidate originally discovered and optimized at The Scripps Research Institute (TSRI), can reduce the frequency of multiple sclerosis relapse. Relapsing multiple sclerosis is a form of the disease where patients experience a periodic worsening of symptoms. Sensory and motor loss of function leads to increased disability, and patients can need a cane or wheelchair. A signature of the disease is the appearance of lesions in the brain, which are linked to inflammation and can show up through MRI detection during active periods of multiple sclerosis relapse. Ozanimod, discovered by TSRI Professors Hugh Rosen and Ed Roberts and their laboratories, acts as a sphingosine 1-phosphate 1 (S1PR1) receptor agonist--modulating S1PR1 signaling and blocking sources of inflammation. Rosen and Roberts went on to co-found Receptos, a clinical stage biopharmaceutical company that took ozanimod into Phase 1, 2 and 3 clinical trials and was then acquired by Celgene. Ozanimod is the first New Chemical Entity discovered from a starting point in the NIH Common Fund Molecular Libraries Initiative to reach and succeed in advanced clinical studies. As reported by Celgene, results from the randomized, Phase 3, double-blind, double-dummy, active-controlled SUNBEAM study among 1,346 participants show that ozanimod met its primary endpoint in reducing annualized relapse rate (ARR) of relapsing multiple sclerosis, compared with an alternate drug treatment called weekly interferon (IFN) β-1a (Avonex®). Administered at doses of both 1 mg and 0.5 mg, ozanimod demonstrated statistically significant and clinically meaningful improvements, compared to Avonex®, for the primary endpoint of ARR and the measured secondary endpoints of the number of MRI-detected lesions and the number of new or enlarging "T2" MRI lesions at after a year of treatment. "It is exciting and rewarding to see the results of this new Phase 3 trial, which confirm the safety profile from the two-year extension data from the Phase 2 RADIANCE study and underscore ozanimod's efficacy in reducing the burden of MS symptoms on patients and their families," said Rosen. "We look forward to seeing the full study results, as well as the results from the Phase 3 study evaluating ozanimod in patients with ulcerative colitis." Scientists involved in the trial plan to present the full Phase 3 trial results at an upcoming international scientific meeting. The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists--including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine--work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www. .


News Article | January 25, 2017
Site: www.techtimes.com

DNA of life on Earth has been made up of only four letters: G, T, C, and A, which together form the code underlying every living entity on the planet. But that’s until now, since scientists have announced the development of the first semi-synthetic organism using an expanded genetic code. Synthesizing a DNA base pair in their 2014 study, the researchers created bacteria that thrive using the expanded “genetic alphabet.” With an additional X and Y for an “unnatural base pair” (UBP), the modified E. coli bacterium maintains a genetic code of six letters. “We’ve made this semisynthetic organism more life-like,” said lead researcher and The Scripps Research Institute professor Floyd Romesberg in a statement, with the hope that the groundbreaking work could lead to bugs that can help produce new drugs in the future. Previously, a UBP could be incorporated into the E. coli’s DNA, but the resulting organisms grew slowly and the UBP was wiped out after rounds of cell division. Now, the team demonstrated that their organism can hold on well to the artificial base pair even as it divides. This stability is deemed important for the organism’s survival, as one’s genetic information need to stay put during one’s lifetime. To do this, the researchers modified what’s known as a nucleotide transporter, which helps the bacteria import the UBP. Used in 2014, the transporter made the organism “very sick,” so the current modification addressed that problem. Next, they optimized the previous version of Y, now better recognized by the enzymes synthesizing DNA molecules during replication of DNA. They then established a “spell check” system for the bug using CRISPR-Cas9, a popular human genome editing tool. The technology proved to be a big one in 2016, showing how it can perform a wealth of functions from helping treat hemophilia in mice to creating mushrooms that don’t turn brown easily. The team used the CRISPR tool to make sure that any cells dropping X and Y would be tagged as a foreign invader, marked for destruction by the organism. Astoundingly, the semi-synthetic organism was able to keep the synthetic base pair in its genome after 60 rounds of division, inspiring hope in the team that it can indefinitely hold on to the base pair. Romesberg clarified, however, that their work is only in single cells and not meant for more complex ones, with zero application at the moment — meaning they can only get the organism to store genetic data at present. The next step is to see how the new genetic code can be transcribed into RNA, which is the molecule necessary to translate DNA into proteins. Synthetic biology expert Paul Freemont from Imperial College London dubbed it a major step in showing how we can engineer a living cell, such as a bacterium, to sustain a base pair not found in nature. This pursues the possibility of semi-synthetic living organisms performing certain functions “that would rely on a distinct genetic code.” The findings were discussed in the journal PNAS. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.

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