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Archive - May 2011

Date

May 16th

Worm’s Amazing Regenerative Capacity Tied to Ancient Gene

Most people don't think worms are spectacular. But the tiny flatworm that Northwestern University scientist Dr. Christian Petersen studies can do something quite spectacular indeed: it can regenerate itself from nearly every imaginable injury, including decapitation. When cut in half, it becomes two worms. This amazing ability of the planarian flatworm to regenerate its entire body from a small wedge of tissue has fascinated scientists since the late 1800s. The worms can regrow any missing cell or tissue -- muscle, neurons, epidermis, eyes, even a new brain. Now Petersen and colleague Peter Reddien of the Massachusetts Institute of Technology (MIT) have discovered that an ancient and seldom-studied gene is critical for regeneration in these animals. The findings may have important ramifications for tissue regeneration and repair in humans. The gene, called notum, plays a key role in the regeneration decision-making process. Protein from this gene determines whether a head or tail will regrow at appropriate amputation sites, the researchers found. "These worms are superstars in regeneration, and we want to learn how they restore missing body parts," said Dr. Petersen, an assistant professor of molecular biosciences in Northwestern's Weinberg College of Arts and Sciences. "We anticipate that understanding the details of how regeneration occurs in nature will ultimately have a broad impact on the repair of human tissue." The study is published in the May 13, 2011 issue of the journal Science. Dr. Petersen, a former postdoctoral fellow in Dr. Reddien's lab, is the first author. Dr. Reddien, associate professor of biology at MIT and the Whitehead Institute for Biomedical Research, is the other author.

Retina Sections Regenerated and Visual Function Increased Using Skin Stem Cells

Scientists from the Schepens Eye Research Institute, an affiliate of Harvard Medical School, are the first to regenerate large areas of damaged retinas and improve visual function using induced pluripotent stem cells (iPSCs) derived from skin. The results of their study, which was published online on April 29, 2011, in PLoS ONE, hold great promise for future treatments and cures for diseases such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and other retinal diseases that affect millions worldwide. "We are very excited about these results," says Dr. Budd A. Tucker, the study's first author. "While other researchers have been successful in converting skin cells into induced pluripotent stem cells and subsequently into retinal neurons, we believe that this is the first time that this degree of retinal reconstruction and restoration of visual function has been detected," he adds. Dr. Tucker, who is currently an Assistant Professor of Ophthalmology at the University of Iowa, Carver College of Medicine, completed the study at Schepens Eye Research Institute in collaboration with Dr. Michael J. Young, the principle investigator of the study, who heads the Institute's regenerative medicine center. Today, diseases such as retinitis pigmentosa and age-related macular degeneration are the leading causes of incurable blindness in the western world. In these diseases, retinal cells, also known as photoreceptors, begin to die and with them the eye's ability to capture light and transmit this information to the brain. Once destroyed, retinal cells, like other cells of the central nervous system have limited capacity for endogenous regeneration. "Stem cell regeneration of this precious tissue is our best hope for treating and someday curing these disorders," says Dr.

Tiny Variation in One Gene May Have Led to Brain Convolutions

The human brain has yet to explain the origin of one its defining features – the deep fissures and convolutions that increase its surface area and allow for rational and abstract thoughts. An international collaboration of scientists from the Yale School of Medicine and Turkey may have discovered an important clue – a tiny variation within a single gene that determines the formation of brain convolutions – they report online on May 15, 2011, in Nature Genetics. A genetic analysis of a Turkish patient whose brain lacks the characteristic convolutions in part of his cerebral cortex revealed that the deformity was caused by the deletion of two genetic letters from three billion in the human genetic alphabet. Similar variations of the same gene, called laminin gamma 3 (LAMC3), were discovered in two other patients with similar abnormalities. "The demonstration of the fundamental role of this gene in human brain development affords us a step closer to solve the mystery of the crown jewel of creation, the cerebral cortex," said Dr. Murat Gunel, senior author of the paper and the Nixdorff-German Professor of Neurosurgery, co-director of the Neurogenetics Program and professor of genetics and neurobiology at Yale. The folding of the brain is seen only in mammals with larger brains, such as dolphins and apes, and is most pronounced in humans. These fissures expand the surface area of the cerebral cortex and allow for complex thought and reasoning without taking up more space in the skull. Such foldings aren't seen in mammals such as rodents or other animals. Despite the importance of these foldings, no one has been able to explain how the brain manages to create them. The LAMC3 gene – involved in cell adhesion that plays a key role in embryonic development – may be crucial to the process.

Chromosome 3 Region Linked to Depression

Researchers at Washington University School of Medicine in St. Louis and King's College London have independently identified a DNA region on chromosome 3 that appears to be related to depression. Major depression affects approximately 20 percent of people at some point during their lives, and family studies have long suggested that depression risk is influenced by genetics. The new studies identify a DNA region containing up to 90 genes. Both studies were published online on May 15, 2011, in the American Journal of Psychiatry. "What's remarkable is that both groups found exactly the same region in two separate studies," says senior investigator Dr. Pamela A. F. Madden, professor of psychiatry at Washington University. "We were working independently and not collaborating on any level, but as we looked for ways to replicate our findings, the group in London contacted us to say, 'We have the same linkage peak, and it's significant.'" Dr. Madden and the other researchers believe it is likely that many genes are involved in depression. While the new findings won't benefit patients immediately, the discovery is an important step toward understanding what may be happening at the genetic and molecular levels, she says. The group at King's College London followed more than 800 families in the United Kingdom affected by recurrent depression. The Washington University group gathered data from 91 families in Australia and another 25 families in Finland. At least two siblings in each family had a history of depression, but the Australian and Finnish participants were studied originally because they were heavy smokers. "Major depression is more common in smokers, with lifetime reports as high as 60 percent in smokers seeking treatment," says lead author Dr. Michele L. Pergadia, research assistant professor of psychiatry at Washington University.

May 15th

KLF14 Is “Master Switch” Gene for Obesity and Diabetes

A team of researchers, led by King's College London and the University of Oxford scientists, has found that a gene linked to type 2 diabetes and cholesterol levels is in fact a 'master regulator' gene, which controls the behavior of other genes found within fat in the body. As fat plays a key role in susceptibility to metabolic diseases such as obesity, heart disease, and diabetes, this study highlights the regulatory gene as a possible target for future treatments to fight these diseases. Published May 15, 2011, in Nature Genetics, the study was one part of a large multi-national collaboration funded by the Wellcome Trust, known as the MuTHER study. It involves researchers from King's College London, University of Oxford, The Wellcome Trust Sanger Institute, and the University of Geneva. DeCODE Genetics also contributed to the results reported in this paper. It was already known that the KLF14 gene is linked to type 2 diabetes and cholesterol levels but, until now, how it did this and the role it played in controlling other genes located farther away on the genome was unknown. The researchers examined over 20,000 genes in subcutaneous fat biopsies from 800 UK female twin volunteers. They found an association between the KLF14 gene and the expression levels of multiple distant genes found in fat tissue, which means it acts as a master switch to control these genes. This was then confirmed in a further independent sample of 600 subcutaneous fat biopsies from Icelandic subjects. These other genes found to be controlled by KLF14 are in fact linked to a range of metabolic traits, including body-mass index (obesity), and cholesterol, insulin, and glucose levels, highlighting the interconnectedness of metabolic traits. The KLF14 gene is special in that its activity is inherited from the mother. Each person inherits a set of all genes from both parents.

Comparative Genomics of Aspergillus Fungi Could Lead to Biorefinery

Fungi play key roles in nature and are valued for their great importance in industry. Consider citric acid, a key additive in several foods and pharmaceuticals produced on a large-scale basis for decades with the help of the filamentous fungus Aspergillus niger. While A. niger is an integral player in the carbon cycle, it possesses an arsenal of enzymes that can be deployed in breaking down plant cell walls to free up sugars that can then be fermented and distilled into biofuel, a process being optimized by U.S. Department of Energy researchers. In work published online ahead of print on May 4, 2011 in Genome Research, a team led by Dr. Scott Baker of the Pacific Northwest National Laboratory compared the genome sequences of two Aspergillus niger strains in order to, among other things, better harness its industrial potential in biofuels applications. As more than a million tons of citric acid are produced annually, the production process involving A. niger is a well understood fungal fermentation process that could inform the development of a biorefinery where organic compounds replace the chemical building blocks normally derived from petroleum. Learning more about the genetic bases of the behaviors and abilities of these two industrially relevant fungal strains, wrote senior author Dr. Baker and his colleagues in the paper, will allow researchers to exploit their genomes towards the more efficient production of organic acids and other compounds, including biofuels. "Aspergillus niger is an industrial workhouse for enzymes and small molecules such as organic acids," said Dr. Baker of the fungus selected for sequencing by the DOE JGI (Department of Energy Joint Genome Institute) in 2005. "Most of the world's citric acid comes from A. niger.

Designer Proteins Target Influenza Virus

A research article in the May 13, 2011 issue of Science demonstrates the use of computational methods to design new antiviral proteins not found in nature, but capable of targeting specific surfaces of flu virus molecules. One goal of such protein design would be to block molecular mechanisms involved in cell invasion and virus reproduction. Computationally designed, surface targeting, antiviral proteins might also have diagnostic and therapeutic potential in identifying and fighting viral infections. The lead authors of the study are Drs. Sarel J. Fleishman and Timothy Whitehead of the University of Washington (UW) Department of Biochemistry, and Dr. Damian C. Ekiert from the Department of Molecular Biology and the Skaggs Institute for Chemical Biology at The Scripps Research Institute. The senior authors are Dr. Ian Wilson from Scripps and Dr. David Baker from the UW and the Howard Hughes Medical Institute. The researchers note that additional studies are required to see if such designed proteins can help in diagnosing, preventing, or treating viral illness. What the study does suggest is the feasibility of using computer design to create new proteins with antiviral properties. "Influenza presents a serious public health challenge," the researchers noted, "and new therapies are needed to combat viruses that are resistant to existing anti-viral medications or that escape the body's defense systems." The scientists focused their attention on the section of the flu virus known as the hemagglutinin stem region. They concentrated on trying to disable this part because of its function in invading the cells of the human respiratory tract.

May 14th

Giant Interneuron Enables Sparse Coding for Odors

The brain is a coding machine: it translates physical inputs from the world into visual, olfactory, auditory, tactile perceptions via the mysterious language of its nerve cells and the networks which they form. Neural codes could in principle take many forms, but in regions forming bottlenecks for information flow (e.g., the optic nerve) or in areas important for memory, sparse codes are highly desirable. Scientists at the Max Planck Institute for Brain Research in Frankfurt have now discovered a single neuron in the brain of locusts that enables the adaptive regulation of sparseness in olfactory codes. This single giant interneuron tracks in real time the activity of several tens of thousands of neurons in an olfactory center and feeds inhibition back onto all of them, so as to maintain their collective output within an appropriately sparse regimen. In this way, representation sparseness remains steady as input intensity or complexity varies. Signals from the world (electromagnetic waves, pressure, chemicals etc) are converted to electrical activity in sensory neurons and processed by neuronal networks in the brain. Insects sense smells via their antennae. Odors are detected by sensory neurons there, and olfactory data are then sent to and processed by the antennal lobes and a region of the brain known as the mushroom bodies. Neurons in the antennal lobes tend to be “promiscuous:” odors are thus represented by specific combinations of neuronal activity. Neurons in the mushroom bodies—they are called Kenyon cells—, however, respond with great specificity and thus extremely rarely. In addition, they generally respond with fewer than three electrical impulses when stimulated with the right odor.

May 12th

Gene Identified for Joubert Syndrome, a Type of Intellectual Disability

A new study involving Canada's Centre for Addiction and Mental Health (CAMH) has found a gene connected with a type of intellectual disability called Joubert syndrome. CAMH Senior Scientist Dr. John Vincent has identified this gene that, when defective, leads to Joubert syndrome. This research is published in the May 13, 2011 issue of Cell. This international study combined Dr. Vincent's gene mapping of a family with Joubert syndrome, with the use of a protein network map established by researchers at Genentech Inc., Stanford University, and the University of California at San Francisco (UCSF). Together, these approaches identified two genes associated with the group of disorders called ciliopathies. Joubert syndrome, which is a ciliopathy, affects brain functioning, resulting in intellectual deficits, movement and coordination problems, and other symptoms such as kidney and eye problems. This syndrome is reported to affect approximately 1 in 100,000 children, although this is likely to be a significant underestimate of the true prevalence. Ciliopathies are caused by genetic defects in a part of the cell called the cilium. The cilium is crucial as it is involved with cell signaling pathways during cell development in different parts of the body. The other ciliopathy gene identified in this study leads to a condition called nephronopthisis, which is also associated with kidney and eye problems. "A defect in any aspect of this molecular pathway may have very similar effects at the clinical level," says Dr. Vincent, who is also head of the Centre for Addiction and Mental Health's Molecular Neuropsychiatry and Development Laboratory. Dr. Vincent's team found defects in the TCTN2 gene occurring in a family in Pakistan, in which four siblings had Joubert syndrome.

May 11th

Personalized Medicine 4.0 Conference: Focus on Pharmacogenomics & Consumer Genetic Testing

This year’s Personalized Medicine Conference (4.0) will be held Thursday, May 26 from 8 am to 7 pm at the South San Francisco Conference Center on the campus of San Francisco State University. This fourth annual conference on personalized medicine focuses on two exciting areas – pharmacogenomics (the right drug, at the right dose, for the right patient, at the right time) and the controversial topic of direct-to-consumer genetic testing, examining the science, the business, and the social dimensions of each. Personalized Medicine 4.0 is a one-day conference and networking opportunity for health and industry professionals, educators, and scientists. Learn how the new genomic medicine will affect your work and your life. Seating is limited. Register now at http://personalizedmedicine.sfsu.edu. For additional information or to sponsor this event, please e-mail dnamed@sfsu.edu or call Arlene Essex at 415-405-4107. Advance registration is $495 through 5/16. Save $100 – Early registration is $395 ending soon! Contact us for academic rates.