Syndicate content

Archive - Oct 2012

Date

October 11th

Chemistry Nobel Awarded for Work on G-Protein-Coupled Receptors (GPCRs)

Robert J. Lefkowitz M.D., a Howard Hughes Medical Institute investigator who has spent his entire 39-year research career at the Duke University Medical Center, is sharing the 2012 Nobel Prize in Chemistry with Brian K. Kobilka, M.D., of Stanford University School of Medicine, who was a post-doctoral fellow in Dr. Lefkowitz’s lab in the 1980s. The Nobel announcement of the prize was made on October 10, 2012. The two scientists are being recognized for their work on a class of cell surface receptors that have become the target of prescription drugs, including antihistamines, ulcer drugs, and beta blockers to relieve hypertension, angina, and coronary disease. The receptors receive chemical signals from the outside and transmit their messages into the cell, providing the cell with information about changes occurring within the body. These particular receptors are called seven-transmembrane G protein-coupled receptors, or just "G-coupled receptors" for short. Serpentine in appearance, G-coupled receptors weave through the surface of the cell seven times. The human genome contains code to make at least 1,000 different forms of these trans-membrane receptors, all of which are quite similar. The receptors also bear a strong resemblance to receptors that detect light in the eyes, smells in the nose, and taste on the tongue. "Bob's seminal discoveries related to G-protein coupled receptors ultimately became the basis for a great many medications that are in use today across many disease areas," said Victor J. Dzau, M.D., Chancellor for Health Affairs and CEO, Duke University Health System. "He is an outstanding example of a physician-scientist whose impact can be seen in the lives of the countless patients who have benefited from his scientific discoveries.

Breakthrough in Fighting Pompe Disease

Adding a third anti-cancer agent to a current drug cocktail appears to have contributed to dramatic improvement in three infants with the most severe form of Pompe disease -- a rare, often-fatal genetic disorder characterized by low or no production of an enzyme crucial to survival. Duke researchers previously pioneered the development of the first effective treatment for Pompe disease via enzyme replacement therapy (ERT). ERT relies on a manufactured enzyme/protein to act as a substitute for the enzyme known to be lacking in patients with a particular disease. In Pompe disease, ERT has been found to reduce heart and muscle damage caused by the absence of the enzyme. In the new study, appearing online on Oct. 11, 2012, in Genetics in Medicine, the Duke team, and collaborators, added a new step to the therapeutic regimen to address complications suffered by a subset of infants with Pompe disease who are treated with ERT. Some infants with Pompe disease who have certain combinations of genetic mutations develop a severe immune response to ERT. Very high levels of antibodies become directed against the enzyme and greatly reduce its therapeutic effect, leading to rapid clinical decline and death. In a January 2012 publication in Genetics in Medicine, the researchers reported success in preventing the immune rejection in Pompe infants who were just beginning ERT. They treated them with a drug cocktail that included low doses of the cancer chemotherapy drugs rituximab and methotrexate, plus the immune booster gammaglobulin to prevent the immune response to the ERT.

October 1st

Laser Scissors and Next-Gen Sequencing Allow Analysis of Gene Activty in Entire Fungal Genomes

With a combination of microscopic laser scissors and modern sequencing methods, biologists at the Ruhr-Universität Bochum (RUB) in Germany have analyzed the activity of genes in the entire genomes of a certain fungi in one fell swoop. Especially with organisms in the millimetre size range, this is a particular challenge because little cell material is available. The scientists of the RUB Department of General and Molecular Botany took advantage of the combined methods to investigate the development of small, multicellular fungi. The results were reported on September 27, 2012 in the open-access journal BMC Genomics. In multicellular organisms, each cell contains the same genetic material, however, often only a fraction of the genes are active (expressed). These differences in gene expression are the cause of variations in the structure and physiology of cells. Gene expression is therefore the key to understanding the development of multicellular organisms. "In large organisms such as plants, it is usually not a problem to get enough starting material to study gene expression," explains Dr. Minou Nowrousian. "In the case of microorganisms, organs often consist of only a few cells, and might be embedded in other tissues from which they are difficult to separate." Therefore, biologists of the research groups of Professor Ulrich Kück and Dr. Nowrousian combined laser microdissection with modern sequencing technologies to analyze the gene activity during the development of certain, just 0.5 millimeters large, sexual structures of fungi. In laser microdissection, scientists cut defined regions of a sample under the light microscope with a laser beam.