Syndicate content

Archive - 2013

December 17th

Labcyte and Finnish Scientists Announce a Collaboration Enabling “Real-Time” Science to Advance Personalized Medicine in Cancer Treatments

Labcyte Inc., headquartered in Sunnyvale, California, and the Institute for Molecular Medicine Finland (FIMM) are collaborating to further the development of personalized medicine in cancer treatment. Labcyte acoustic liquid handling technology (see image) has already revolutionized small-molecule research. Now, FIMM, a European leader in advanced research for new cancer therapies, will apply the technology extensively in its personalized medicine programs. “FIMM’s groundbreaking use of acoustic liquid handling will demonstrate the technology’s role in genetic research,” said Mark Fischer-Colbrie, CEO of Labcyte. “FIMM has successfully used Labcyte acoustic liquid handling technology to generate better data and drive down costs in small-molecule screening for the past three years. This collaboration with such a well-regarded institute will facilitate breakthroughs in personalized medicine.” FIMM uses large sample sets with links to detailed patient records and genetic data to discover personalized treatment options at a faster pace. “We see an enormous potential in expanding our use of Labcyte acoustic dispensing technology to help discover specialized leukemia treatments,” said Professor Olli Kallioniemi, director of FIMM. “This research is based on high-throughput drug sensitivity and resistance testing of leukemic cells taken from patients. This new initiative will bring us closer to the clinic and closer to patients. Our aim is to find alternate treatment options for patients who simultaneously undergo treatment in the clinic,” said Professor Kallioniemi.

December 16th

Research Shows How Household Dogs Protect Children Against Asthma and Infection

Children's risk for developing allergies and asthma is reduced when they are exposed in early infancy to a dog in the household, and now researchers have discovered a reason why. Exposure of mice to dust from houses where canine pets are permitted both indoors and outdoors can reshape the community of microbes that live in the mouse gut — collectively known as the gastrointestinal microbiome — and also diminish immune system reactivity to common allergens, according to a new study by researchers led by Susan Lynch, Ph.D., associate professor with the Division of Gastroenterology at the University of California at San Francisco (UCSF), and Nicholas Lukacs, Ph.D., professor in the Department of Pathology at the University of Michigan. The scientists also identified a specific bacterial species within the gut that is critical to protecting the airways against both allergens and viral respiratory infection. The study, funded by the National Institute of Allergy and Infectious Diseases (NIAID), was published online on December 16, 2013 in PNAS and involves a multi-disciplinary group of researchers from UCSF, the University of Michigan, the Henry Ford Health System ,and Georgia Regents University. The results were obtained in studies of mice challenged with allergens after earlier exposure to dust from homes with dogs, but the results also are likely to explain the reduced allergy risk among children raised with dogs from birth, according to the study leaders. In their study, the scientists exposed mice to cockroach or protein allergens. They discovered that asthma-associated inflammatory responses in the lungs were greatly reduced in mice previously exposed to dog-associated dust, in comparison to mice that were exposed to dust from homes without pets or mice not exposed to any dust.

December 15th

Disrupting of Quorum-Sensing Messages May Combat Sleeping Sickness

A new discovery by scientists could help combat the spread of sleeping sickness. Insights into how the parasites that cause the disease are able to communicate with one another could help limit the spread of the infection. The findings suggest that new drugs could be designed to disrupt the flow of messages sent between these infectious microorganisms. Sleeping sickness – so named because it disrupts sleep patterns – is transmitted by the bite of the tsetse fly, and more than 69 million people in Africa are at risk of infection. Untreated, it can damage the nervous system, leading to coma, organ failure, and death. During infection, the parasites – known as African trypanosomes – multiply in the bloodstream and communicate with each other by releasing a small molecule. When levels of this molecule become sufficiently high, this acts as a signal for the parasites to stop replicating and to change into a form that can be picked up by biting flies and spread. A team led by researchers at the University of Edinburgh was able to uncover key components of the parasites' messaging system. They used a technique known as gene silencing, to identify those genes that are used to respond to the communication signals and the mechanisms involved. Professor Keith Matthews, of the University of Edinburgh's School of Biological Sciences, who led the research, said: "Parasites are adept at communicating with one another to promote their survival in our bodies and ensure their spread – but by manipulating their messages, new ways to combat these infections are likely to emerge." The research, carried out in collaboration with the University of Dundee, was published online on December 15, 2013 in Nature, and funded by the Wellcome Trust.

Researcher Traces History of American Urban Squirrel

Until recently, Dr. Etienne Benson, an assistant professor in the University of Pennsylvania's Department of History and Sociology of Science, has trained his academic eye on the history of conservation of large, charismatic wildlife, such as tigers, grizzly bears, and orcas. With his latest publication, however, he consciously chose to investigate a creature that may be considered less exotic, and is certainly smaller. "I wanted to write about something a bit closer to home, about things we see and encounter every day," Dr. Benson said. "I wanted to shift the focus to the urban and the quotidian and, in some sense, the trivial, to see what we can learn by looking at trivial nature, or nature that is at risk of being interpreted as trivial." So he turned his attention to the squirrel. His paper, "The Urbanization of the Eastern Gray Squirrel in the United States," published in the December 2013 issue of the Journal of American History (also note podcast at link below), examines how the now-ubiquitous bushy-tailed creatures found homes in American cities, and how their presence there altered people's conceptions of nature and community. Dr. Benson explains that though many people may think that squirrels have simply persisted in urban landscapes since Europeans arrived in the U.S., their presence is actually the result of intentional introductions. "By the mid-19th century, squirrels had been eradicated from cities," he said. "In order to end up with squirrels in the middle of cities, you had to transform the urban landscape by planting trees and building parks and changing the way that people behave. People had to stop shooting squirrels and start feeding them." In researching the history of squirrels in American cities, Dr.

Extensive Variability in Olfactory Receptors Influences Human Odor Perception

A difference at the smallest level of DNA -- one base pair coded for by one gene -- can determine whether you find a given smell pleasant. A different base pair coded for by the same gene in your friend's body could mean he finds the same odor offensive, according to researchers at Duke University and collaborators from Monell Chemical Sciences Center, the University of Pennsylvania School of Medicine, and Rockefeller University. There are approximately 400 genes coding for the receptors in our noses, and according to the 1000 Genomes Project, there are more than 900,000 variations of those genes. These receptors control the sensors that determine how we smell odors. A given odor will activate a suite of receptors in the nose, creating a specific signal for the brain. But the receptors don't work the same for all of us, said Hiroaki Matsunami, Ph.D., associate professor of molecular genetics and microbiology at the Duke University School of Medicine. In fact, when comparing the receptors in any two people, they should be about 30 percent different, said Dr. Matsunami, who is also a member of the Neurobiology Graduate Program and the Duke Institute for Brain Sciences. "There are many cases when you say you like the way something smells and other people don't. That's very common," Dr. Matsunami said. But what the researchers found is that no two people smell things the same way.

December 13th

Stunning Discovery of Second DNA Code, Written Over the First

Scientists have discovered a second code hiding within DNA. This second code contains information that changes how scientists read the instructions contained in DNA and interpret mutations to make sense of health and disease. A research team led by Dr. John Stamatoyannopoulos, University of Washington (UW) associate professor of genome sciences and of medicine, made the discovery. The findings are reported in the December 13, 2013 issue of Science. The work is part of the Encyclopedia of DNA Elements Project, also known as ENCODE. The National Human Genome Research Institute funded the multi-year, international effort. ENCODE aims to discover where and how the directions for biological functions are stored in the human genome. Because the genetic code was deciphered in the 1960s, scientists have assumed that it was used exclusively to write information about proteins. UW scientists were stunned to discover that genomes use the genetic code to write two separate languages. One describes how proteins are made, and the other instructs the cell on how genes are controlled. One language is written on top of the other, which is why the second language remained hidden for so long. “For over 40 years, we have assumed that DNA changes affecting the genetic code solely impact how proteins are made,” said Dr. Stamatoyannopoulos. “Now we know that this basic assumption about reading the human genome missed half of the picture. These new findings highlight that DNA is an incredibly powerful information storage device, which nature has fully exploited in unexpected ways.” The genetic code uses a 64-letter alphabet called codons. The UW team discovered that some codons, which they called duons, can have two meanings, one related to protein sequence, and one related to gene control. These two meanings seem to have evolved in concert with each other.

December 9th

Sickle Cell Disease May Be Reversed by Flipping Hemoglobin Switch

Hematology researchers at The Children's Hospital of Philadelphia have manipulated key biological events in adult blood cells to produce a form of hemoglobin normally absent after the newborn period. Because this fetal hemoglobin is unaffected by the genetic defect in sickle cell disease (SCD), the cell culture findings may open the door to a new therapy for the debilitating blood disorder. "Our study shows the power of a technique called forced chromatin looping in reprogramming gene expression in blood-forming cells," said hematology researcher Jeremy W. Rupon, M.D., Ph.D., of The Children's Hospital of Philadelphia. "If we can translate this approach to humans, we may enable new treatment options for patients." Dr. Rupon presented the team's findings on December 8, 2013 at a press conference during the annual meeting of the American Society of Hematology (ASH) in New Orleans. Dr. Rupon worked in collaboration with a former postdoctoral fellow, Wulan Deng, Ph.D., in the laboratory of Gerd Blobel, M.D., Ph.D. Hematologists have long sought to reactivate fetal hemoglobin as a treatment for children and adults with SCD, the painful, sometimes life-threatening genetic disorder that deforms red blood cells and disrupts normal circulation. In the normal course of development, a biological switch flips during the production of hemoglobin, the oxygen-carrying component of red blood cells. Regulatory elements in DNA shift the body from producing the fetal form of hemoglobin to producing the adult form instead. This transition occurs shortly after birth. When patients with SCD undergo this transition, their inherited gene mutation distorts adult hemoglobin, forcing red blood cells to assume a sickled shape. In the current study, Dr. Rupon and Dr.

December 7th

Stunning Results in Personalized, Cell-Based Gene Therapy of Leukemias

Three and a half years after beginning a clinical trial which demonstrated the first successful and sustained use of genetically engineered T cells to fight leukemia, a research team from the Perelman School of Medicine at the University of Pennsylvania and the Children's Hospital of Philadelphia announced on December 7, 2013 the latest results of studies involving both adults and children with advanced blood cancers that have failed to respond to standard therapies. The findings from the first 59 patients who received this investigational, personalized cellular therapy, known as CTL019, will be presented during the American Society of Hematology's Annual Meeting and Exposition in New Orleans. Two of the first three chronic lymphocytic leukemia (CLL) patients who participated in the study, which started in the summer of 2010, remain in remission, with tests revealing reprogrammed cells still circulating in their bodies, on guard to combat tumor cells that may reappear in the future. Additional highlights of the new research results include an 89 percent complete response rate among adult and pediatric patients with acute lymphoblastic leukemia (ALL). "In a very short time, we've learned so much about how CTL019 works and how powerful it can be," said the research team's leader, Carl H. June, M.D., Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penn's Abramson Cancer Center.

December 7th

PKM2 Controls Mitosis, Saving Cancer Cells from Death and Promoting Brain Tumor Growth

Researchers have caught a protein they previously implicated in a variety of cancer-promoting roles performing a vital function in cell division, survival, and development of brain tumors. In a paper published online on December 5, 2013 in Molecular Cell, Zhimin Lu, Ph.D., professor of Neuro-Oncology at The University of Texas MD Anderson Cancer Center and colleagues report how a tumor-specific protein flips a crucial switch in an irregular mechanism for mitosis that allows cancer cells to safely divide. "Our research shows that tumor cells rely heavily on a distinct mechanism for orderly cell division that's driven by oncogene-induced pyruvate kinase M2 (PKM2)," Dr. Lu said. After a cell begins division by replicating all of its chromosomes, mitosis separates them into two identical sets of chromosomes for both cells. After mitosis, cytokinesis completes cell divison. "Without PKM2 regulating a checkpoint in mitosis, the tumor cell would not successfully divide," Dr. Lu said. "Depleting PKM2 led to an uneven distribution of DNA to the two new cells, triggering programmed cell death, or apoptosis, of those cells after division. This new, additional role for PKM2 in cancer development and survival may provide a molecular basis for diagnosing and treating tumors with upregulated PKM2," Dr. Lu said. He and his colleagues have now identified four specific mechanisms by which PKM2 promotes cancer development. The key relationship between PKM2 activity and mitosis uncovered by the researchers led to rapid brain tumor growth when activated in mice, while blocking it reduced tumor volume by 83 percent and more than doubled survival from about 20 days to beyond 40 days.

December 6th

Researchers May Have Discovered Causes for Disabling Meniere's Disease

Researchers at the University of Colorado School of Medicine may have determined what causes Meniere's disease and how to attack it. According to Carol Foster, M.D., from the department of otolaryngology and Robert Breeze, M.D., a neurosurgeon, there is a strong association between Meniere's disease and conditions involving temporary low blood flow in the brain such as migraine headaches. Meniere's disease affects approximately 3 to 5 million people in the United States. It is a disabling disorder resulting in repeated violent attacks of dizziness, ringing in the ear, and hearing loss that can last for hours and can ultimately cause permanent deafness in the affected ear. Up until now, the cause of the attacks has been unknown, with no theory fully explaining the many symptoms and signs of the disorder. "If our hypothesis is confirmed, treatment of vascular risk factors may allow control of symptoms and result in a decreased need for surgeries that destroy the balance function in order to control the spell" said Dr. Foster. "If attacks are controlled, the previously inevitable progression to severe hearing loss may be preventable in some cases." Dr. Foster explains that these attacks can be caused by a combination of two factors: 1) a malformation of the inner ear, endolymphatic hydrops (the inner ear dilated with fluid) and 2) risk factors for vascular disease in the brain, such as migraine, sleep apnea, smoking and atherosclerosis. The researchers propose that a fluid buildup in part of the inner ear, which is strongly associated with Meniere attacks, indicates the presence of a pressure-regulation problem that acts to cause mild, intermittent decreases of blood flow within the ear.