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Archive - Sep 2011

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September 11th

Researchers Use New Tool to Counter Drug Resistance in Multiple Myeloma

"Acquired drug resistance" (ADR) is a major problem encountered in treating some forms of cancer. The ability to monitor the proteins involved in drug resistance has been a hurdle facing cancer researchers. However, a team of researchers at Moffitt Cancer Center in Tampa, Florida, and colleagues, are pioneering promising research utilizing a monitoring technology that could provide a better understanding of ADR and assist in clinical decision-making for developing individualized patient treatments for multiple myeloma. The technique has potentially broader applications to other types of cancer as well. The team’s research results are published in the October issue of Molecular and Cellular Proteomics and were first published online on August 16, 2011. "Multiple myeloma is an incurable malignancy in the bone marrow," said Dr. John M. Koomen, assistant member in Molecular Oncology and Experimental Therapeutics and scientific director of Moffitt's Proteomics Core Facility. "While patients with multiple myeloma initially respond to chemotherapy, they eventually develop drug resistance from a variety of factors. We want to be able to detect acquired drug resistance, so that we can change the therapeutic regimen to meet the needs of the patient." The research team has employed a method called Liquid Chromatography Multiple Reaction Monitoring (LC-MRM) to monitor proteins determined to be involved in ADR. This was based on the prior myeloma research conducted at Moffitt by Dr. William S. Dalton, Moffitt's CEO and center director, and colleagues. Among the factors in ADR is an alteration in the "apoptopic machinery" of cells. Apoptosis, or programmed cell death, is determined by the interaction of anti-apoptosis and pro-apoptosis proteins in response to both external and internal stimuli.

September 7th

Endangered Horse Has Ancient Origins and Rich Genetic Diversity

An endangered species of horse -- known as Przewalski's horse -- is much more distantly related to the domestic horse than researchers had previously hypothesized, reports a team of investigators led by Dr. Kateryna Makova, a Penn State University associate professor of biology. The scientists tested the portion of the genome passed exclusively from mother to offspring -- the mitochondrial DNA -- of four Przewalski's horse lineages and compared the data to DNA from the domestic horse (Equus caballus). They concluded that, although previous scientists had assumed that Przewalski's horse and the domestic horse had diverged around the time that horses were domesticated -- about 6,000 to 10,000 years ago -- the real time of the two species' divergence from one another is much more ancient. The data gleaned from the study also suggest that present-day Przewalski's horses have a much more diverse gene pool than previously hypothesized. The new study's findings could be used to inform conservation efforts to save the endangered horse species, of which only 2,000 individuals remain in parts of China and Mongolia, and in wildlife reserves in California and the Ukraine. The paper will be published in the journal Genome Biology and Evolution. It was first published online, before print, on July 29, 2011. Przewalski's horse -- a stocky, short-maned species named after a Russian explorer who first encountered the animal in the wild -- became endangered during the middle of the last century when the species experienced a population bottleneck -- an evolutionary event in which many or most members of a population or a species die. "Sadly, this bottleneck was the result of human activity," Dr. Makova explained.

September 6th

Next-Gen Sequencing Reveals a Gene for Mitochondrial Disease

In Leigh syndrome, infants are born apparently healthy only to develop movement and breathing disorders that worsen over time, often leading to death by the age of 3. The problem is that the mitochondria responsible for powering their cells can't keep up with the demand for energy in their developing brains. Now, researchers reporting in the September issue of Cell Metabolism, a Cell Press publication, have discovered a new genetic defect that can lead to the disease. The findings were made by sequencing a subset of about 1,000 genes encoding proteins active in the mitochondria in just two individuals with Leigh syndrome. "This shows the huge potential of sequencing technologies to improve diagnosis," says Dr. David Thorburn of Murdoch Childrens Research Institute in Australia. "It's an all-comers approach that can be applied to individuals, even with no family history." Leigh syndrome is the most common recognized mitochondrial disease of childhood, and the new genetic discovery adds to a growing list of about 40 genes known to cause Leigh syndrome when mutated. The gene the researchers uncovered encodes an enzyme active in mitochondria known as MTFMT (for mitochondrial methionyl-tRNA formyltransferase). (Mitochondria carry DNA of their own and their operation depends on a combination of proteins encoded locally and others encoded in the nuclear genome of a cell and imported.) The MTFMT enzyme encoded in the mitochondrial DNA is responsible for converting a transfer RNA (tRNA) into a form used to initiate protein translation. Without that enzyme, mitochondria fail to translate proteins efficiently leading to the symptoms recognized as Leigh syndrome. Studies in patient skin cells showed that the defects in translation could be corrected by replacing the MTFMT gene.

September 1st

First Lizard Genome Sequenced

The green anole lizard is an agile and active creature, and so are elements of its genome. This genomic agility and other new clues have emerged from the full sequencing of the lizard's genome and may offer insights into how the genomes of humans, mammals, and their reptilian counterparts have evolved since mammals and reptiles parted ways 320 million years ago. The researchers who completed this sequencing project reported their findings August 31, 2011, online in the journal Nature. The green anole lizard (Anolis carolinensis) – a native of the Southeastern United States – is the first non-bird species of reptile to have its genome sequenced and assembled. Broad Institute researchers have assembled and analyzed more than 20 mammalian genomes – including those of some of our closest relatives – but the genetic landscape of reptiles remains relatively unexplored. "Sometimes you need to be at a certain distance in order to learn about how the human genome evolved," said Dr. Jessica Alföldi, co-first author of the paper and a research scientist in the vertebrate genome biology group at the Broad Institute. "You have to look out further than you were looking previously." Lizards are more closely related to birds – which are also reptiles – than to any of the other organisms whose genomes have been sequenced in full. Like mammals, birds and lizards are amniotes, meaning that they are not restricted to laying eggs in water. "People have been sequencing animals from different parts of the vertebrate tree, but lizards had not been previously sampled," said Dr. Kerstin Lindblad-Toh, scientific director of vertebrate genome biology at the Broad and senior author of the Nature paper.