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Archive - May 15, 2011

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.