Syndicate content

Archive - 2010

Date

February 21st

Parasitic Wasps May Aid Pest Control Efforts

Parasitoid wasps kill pest insects, but their existence is largely unknown to the public. Now, scientists have sequenced the genomes of three parasitoid wasp species, revealing many features that could be useful in pest control and medicine, and in the enhancement of our understanding of genetics and evolution. "Parasitic wasps attack and kill pest insects, but many of them are smaller than the head of a pin, so people don't even notice them or know of their important role in keeping pest numbers down," said Dr. John Werren, from the University of Rochester, a co-leader of the study along with Dr. Stephen Richards of the Baylor College of Medicine. "There are over 600,000 species of these amazing critters, and we owe them a lot. If it weren't for parasitoids and other natural enemies, we would be knee-deep in pest insects.” Parasitoid wasp females are like "smart bombs" that seek out and kill only specific kinds of insects, said Dr. Werren. "Therefore, if we can harness their full potential, they would be vastly preferable to chemical pesticides, which broadly kill or poison many organisms in the environment, including us." Parasitoid wasps are four times smaller than the common fruit fly. The females seek out specific insect, tick, or mite hosts, inject venom and lay their eggs, with the wasp young emerging to devour the host insect; traits that make the wasps valuable assets as agents for biological control. Although their size is insignificant, the importance of parasitoid wasps in the control of populations of agricultural pests is crucial. Thanks to these insects billions of dollars’ worth of crops is saved each year.

Carnivorous Plants May Yield Anti-Fungal Compounds

The sticky liquid-filled pitchers of carnivorous plants contain anti-fungal compounds that may prove useful for combating fungal diseases in humans, according to research being carried out at Tel Aviv University in Israel. "To avoid sharing precious food resources with other micro-organisms such as fungi, the carnivorous plant has developed a host of agents that act as natural anti-fungal agents," said Dr. Aviah Zilberstein, an author of the report. "In the natural habitat of the tropics, competition for food is fierce, and the hot, moist environment is perfect for fungi, which would also love to eat the plant's insect meal.” In a study conducted together with Dr. Haviva Eilenberg, Dr.Esther Segal, and Dr. Shmuel Carmeli; Dr. Zilberstein and her colleagues found that unusual secondary metabolites from the pitchers of the carnivorous Nepenthes khasiana plant (originally found in India) were effective against pathogens responsible for widespread fungal infections of people in hospitals. "The pitcher of the carnivorous plant produces these compounds in a gland," said Dr. Zilberstein. Until now, no one has published or discussed the anti-fungal metabolites found in the trap liquid of this plant, she said. Currently there is a need for additional, broadly effective anti-fungal drugs. Even mildly severe forms of athlete's foot or other skin fungal infections lack effective treatments. The problem becomes more severe at hospitals, where thousands of Americans die each year from secondary fungal infections they acquire during their stays as patients.

February 19th

Gene Variations Associated with Endurance Running Ability

Scientists have shown that elite endurance runners are more likely to have particular variations (SNPs) of the NRF2 (nuclear respiratory factor 2) gene than are elite sprinters. Non-elite endurance runners were also more likely to have these NRF2 variations compared to sprinters, although the difference was not as pronounced. “These findings suggest that harboring this specific genotype might increase the probability of being an endurance athlete,” said lead author Dr. Nir Eynon of the Wingate Institute in Israel. The authors said that their data supports the notion that these specific gene variants might belong to a growing group of SNPs that are associated with endurance performance. The researchers investigated the NRF2 gene because previous studies had shown that it might play a role in endurance performance as it helps produce new mitochondria, a key cellular structure that produces energy. Earlier studies had also shown that the NRF2 gene can reduce the harmful effects of oxidation and inflammation, which increase during exercise. The researchers noted that their study shows an association between the gene variations and endurance, but does not establish a cause-effect relationship. Future studies are needed to unravel exactly what role the NRF2 gene plays in athletic performance. The current study is part of a larger body of research that is exploring the human genome and which aims to understand the genetic underpinnings of athletic performance. The results were published online in Physiological Genomics on December 22, 2009. The Sports Illustrated photo shows American marathon runner Bill Rodgers in 1979. [Press release] [Physiological Genomics abstract]

Panda Genome Sequenced—Reveals Clues to Bamboo Preference

Using next-generation sequencing technology, a Chinese-led international team has generated a draft genome sequence for the giant panda. The results provide clues to the panda’s predilection for a bamboo diet and demonstrate the feasibility of using next-generation sequencing technologies for accurate, cost-effective, and rapid de novo assembly of large eukaryotic genomes. The authors noted that insights gleaned from the giant panda genome sequence may aid conservation efforts for the endangered species. Although giant pandas are known for their largely bamboo diet, the researchers discovered that the animal actually lacks the genes necessary for compete digestion of this staple food source. Dr. Michael Bruford, an author of the report, noted that "the panda is a true bear and is a carnivore, so it possesses the genes necessary for being a meat-eater and yet its diet is almost exclusively herbivorous. This may suggest that it relies on microbes in its gut to digest bamboo rather than on anything in its genetic make-up. Taste is also important when it comes to the development of dietary habits and the sequencers discovered mutations in the panda's T1R1 gene which may affect its ability to taste meat, one possible explanation for why a potential carnivore would rely on a strict bamboo diet." The study found no signs of the low degree of variation that is usually linked to inbreeding and, in spite of the panda's low reproduction rate, the study identified nearly all the reproduction genes critical for mammalian gonad function and development. These results support the potential for successful survival despite the small population size of the species. Dr. Burford noted, "The panda is at high risk of extinction, with current estimates putting total population figures at less than 3,000.

February 19th

Novel Method of Transcription Regulation Seen in Malaria Parasite

In trying to understand how the human malaria parasite (Plasmodium falciparum) multiplies in red blood cells, a research team has discovered that a kind of "histone crash" takes place--a massive breakdown of the chromatin architecture that explains how the parasite can extensively and rapidly replicate its DNA and coding genes. "If this mechanism can be stopped," said Dr. Karine Le Roch, an assistant professor of cell biology and neuroscience at the University of California-Riverside, and senior author of the report, "Plasmodium replication would cease or be severely inhibited, thus controlling the spread of malaria." "Dr. Le Roch's findings document a global mechanism mediating significant changes in gene expression as the parasites transition through developmental stages in the human hosts," said Dr. Anthony A. James, a distinguished professor of microbiology & molecular genetics and molecular biology & biochemistry at the University of California-Irvine, who was not involved in the research. "As well as being a major basic discovery, this provides a basis for probing the mechanisms for novel drug development." The current study was spurred, in part, by an earlier observation that, in Plasmodium falciparum, specific transcription factors are apparently under-represented relative to the size of the parasite’s genome, and by the fact that mechanisms underlying transcriptional regulation in Plasmodium have remained controversial. “Our results demonstrate that the processes driving gene expression in Plasmodium challenge the classical eukaryotic model of transcriptional regulation occurring mostly at the transcription initiation level. We found in our experiments that histones are massively evicted everywhere in the Plasmodium genome, resulting in most of the Plasmodium genes to be transcribed at once," said Dr. La Roch.

Many Copy Number Variations Universal Among Diverse Tumors

An international team of researchers has created a genome-scale map of 26 different cancers, revealing more than 100 genomic sites where DNA from tumors is either missing or abnormally duplicated compared to normal tissues. The study, the largest of its kind, finds that most of these genetic abnormalities are not unique to one form of cancer, but are shared across multiple cancers. "Our findings show that many genome alterations are universal across different cancers. Although this has been known for some types of changes, the degree to which so many alterations are shared was pretty surprising to us," said senior author Dr. Matthew Meyerson, a professor of pathology at the Dana-Farber Cancer Institute and senior associate member of the Broad Institute of Harvard and MIT. "It suggests that, in the future, a driving force behind cancer treatment will be common genomic alterations, rather than tumors' tissue of origin." In 2004, a scientific team led by researchers at the Dana-Farber Cancer Institute and the Broad Institute launched a project to systematically map genetic changes across different cancers. They focused on a particular type of DNA change in which segments of a tumor's genome are present in abnormal numbers of copies. Instead of the usual two copies, tumors often carry several copies of one piece of DNA (an "amplification") or may lack it altogether (a "deletion"). These genetic abnormalities are known as somatic copy-number alterations or SCNAs. As the foundation for their analysis, the scientists collected over 2,500 cancer specimens representing more than two dozen cancer types, including lung, prostate, breast, ovarian, colon, esophageal, liver, brain, and blood cancers.

Study Distinguishes Between “Driver” and “Passenger” Cancer Mutations

A new study of mutations in cancer genomes suggests how researchers can begin to distinguish the “driver” mutations that push cells towards cancer from the “passenger” mutations that are by-products of cancer cell development. The study also shows that at least one in nine genes, on average, can be removed from human cancer cells without killing the cells. This is in sharp contrast to the corresponding figure for genes in normal human cells [X chromosome (1 in 100 genes); normal human genome (1 in 50 genes)]. Thus, cancer cells seem to be more tolerant to gene loss than the cells of healthy people and can lose a much greater proportion of their genes without losing the ability to live and grow. Many cancer genomes are riddled with mutations. The vast majority of these are likely to be passengers—i.e., mutations that don't contribute to the development of cancer, but have occurred during the growth of the cancer--while a small minority are the critical drivers of cancer growth and proliferation. The challenge of efficiently picking out the guilty drivers in the huge set of mutations found in a cancer genome has yet to be fully met. "It is essential that we can distinguish the drivers from the passengers because knowing the driver mutations, and hence the critical genes they are in, leads to understanding of the cellular processes that have been subverted in cancers, and hence to new drugs," explained the Wellcome Trust Sanger Institute’s Dr. Michael Stratton, senior author of the report. "Our study provides one example of how researchers can sift through the large numbers of a particular type of mutation present in cancer genomes in order to distinguish drivers from passengers."

February 18th

Additional Drug Reduces Lesions in Relapsing Multiple Sclerosis

An international team of researchers has found that adding a humanized monoclonal antibody called daclizumab to standard treatment reduces the number of new or enlarged brain lesions in patients with relapsing multiple sclerosis (MS). Daclizumab is specific for CD25, a protein that is expressed on activated T cells, and binding of daclizumab to CD25 results in selective inhibition of these activated T cells. Daclizumab treatment has been studied in patients with human autoimmune conditions, such as MS, that are characterized by abnormal T-cell responses. "Previous research has shown that treatment with daclizumab reduced multiple sclerosis disease activity," said Dr. John W. Rose, professor of neurology at the University of Utah School of Medicine, and senior author on the current article. "Our work in the CHOICE trial [a Phase 2, randomized, double-blinded, placebo-controlled clinical study] shows that daclizumab significantly reduces MS lesion formation in people with active relapsing disease." In addition to finding that add-on treatment with high-dose daclizumab resulted in a significantly lower number of new or enlarged MS lesions, the researchers found that patients treated with either high- or low-dose daclizumab had a seven to eight times higher number of immune cells called CD56bright natural killer cells (NK cells). Previous research has shown that untreated MS patients have lower numbers of these NK cells than healthy individuals. "Several lines of evidence point to a potential function for CD56bright natural killer cells in regulating the immune system," explained Dr. Rose.

Genome-Based Blood Tests May Usher in Personalized Medicine for Cancer

Data from the whole-genome sequencing of tumors from individual cancer patients may be used to develop individualized blood tests that can help physicians tailor treatments to the individual patient, according to results reported by researchers from Johns Hopkins and Life Technologies. The genome-based blood tests, believed to be the first of their kind, may be used to monitor tumor levels after therapy and determine cancer recurrence. This ground-breaking work may help bring the age of personalized medicine right to the cancer patient’s bedside. The sequencing in this project was carried out using the SOLiD next-generation sequencing platform (photo) from Life Technologies."We believe this is the first application of newer generations of whole-genome sequencing that could be clinically useful for cancer patients," says Dr. Victor Velculescu, co-director of the cancer biology program at Johns Hopkins and senior author of the report. "Using this approach, we can develop biomarkers for potentially any cancer patient." In their study, the scientists scanned the genomes of patients' tumors looking for alterations that they say most researchers have not been looking for—i.e., rearrangements of large chunks of DNA rather than changes in a single DNA letter among billions of others. Such DNA rearrangements are widely known to occur exclusively in cancer cells, not normal ones, making them ideal biomarkers for cancer. The researchers call their new approach Personalized Analysis of Rearranged Ends (PARE). "PARE uses genetic characteristics unique to the tumor to monitor disease progression. By exploiting rearrangements specific to the patient's tumor, we have developed a personalized approach for detection of residual disease," said lead author Rebecca Leary, a graduate student at the Johns Hopkins Kimmel Cancer Center.

February 17th

Mystery of King Tut’s Death Possibly Solved

A combination of bone disease and malaria infection likely contributed to the early death of Egypt’s King Tutankhamun, according to researchers who used a combination of anthropological, radiological, and DNA-based genetic studies to analyze the king’s mummy. The scientists also putatively identified other members of Tutankhamun’s immediate lineage, including his father, mother, and a grandmother. The 18th dynasty (circa 1550-1295 B.C.) of the New Kingdom (mid-16th to early 11th century B.C.) was one of the most powerful royal houses of ancient Egypt, and included the reign of Tutankhamun, probably the most famous of all pharaohs, although his tenure was brief. He died in the ninth year of his reign, circa 1324 B.C., at age 19 years. "Little was known of Tutankhamun and his ancestry prior to Howard Carter's discovery of his intact tomb (KV62) in the Valley of the Kings in 1922, but his mummy and the priceless treasures buried with him, along with other important archeological discoveries of the 20th century, have provided significant information about the boy pharaoh's life and family," the researchers wrote. With regard to their current research, the scientists noted that "several pathologies, including Kohler disease II (bone disorder), were diagnosed in Tutankhamun; none alone would have caused death. Genetic testing for STEVOR, AMA1, or MSP1 genes specific for Plasmodium falciparum (the malaria parasite) revealed indications of malaria tropica in four mummies, including Tutankhamun's. These results suggest avascular bone necrosis (condition in which the poor blood supply to the bone leads to weakening or destruction of an area of bone), in conjunction with the malarial infection as the most likely cause of death in Tutankhamun.