Parasitic Worm Genome Uncovers Potential Drug Targets

Aug. 28, 2013 — Researchers have identified five enzymes that are essential to the survival of a parasitic worm that infects livestock worldwide and is a great threat to global food security. Two of these proteins are already being studied as potential drug targets against other pathogens.

The team sequenced the genome of Haemonchus contortus, or the barber pole worm, a well-studied parasitic worm that resides in the gut of sheep and other livestock globally. This genome could provide a comprehensive understanding of how treatments against parasitic worms work and point to further new treatments and vaccines.

The Barber pole worm or H. contortus is part of a family of gastrointestinal worms that are endemic on 100% of farms and are estimated to cost the UK sheep industry alone more than £80 million pounds each year. H. contortus has become resistant to all major treatments against parasitic worms, so its genome is a good model to understand how drug resistance develops in this complex group of closely related parasites and will also reveal further potential drug and vaccine targets.

“Our reference genome allows researchers to understand how H. contortus and other worms of this type acquire resistance to a wide range of anthelmintics – the drugs used to treat worm infections,” says Dr James Cotton, senior author from the Wellcome Trust Sanger Institute. “Seeing a common theme of drug resistance in this well-characterised worm is extremely important because both people and animals are reliant on so few treatments against parasitic worms.”

The team sequenced the genome of a strain of H contortus that was susceptible to all major classes of drugs against parasitic worms. By comparing this sequence with that of worms that have acquired drug resistance, the researchers expect to reveal a wealth of information about how and why resistance has occurred.

“The H. contortus genome provides a rich and essential platform for future research in this and other types of parasitic worms,” says Professor Neil Sargison, author from the University of Edinburgh, Royal (Dick) School of Veterinary Studies. “With the world population set to exceed nine billion by the year 2050, improving the security of our food supply is crucial. Getting to grips with genomes such as that of H. contortus, is our best option to tackle the issue of drug resistance and develop new drugs against parasitic worms to address this issue.”

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Obesity Reversed in Mice by Manipulating Production of an Enzyme

ScienceDaily (Dec. 5, 2012) — Approximately 68 percent of U.S. adults are overweight or obese, according to the National Cancer Institute, which puts them at greater risk for developing cancer, cardiovascular disease, diabetes and a host of other chronic illnesses. But an international team of scientists led by Virginia Commonwealth University Massey Cancer Center researcher Andrew Larner, M.D., Ph.D., has successfully reversed obesity in mice by manipulating the production of an enzyme known as tyrosine-protein kinase-2 (Tyk2). In their experiments, the scientists discovered that Tyk2 helps regulate obesity in mice and humans through the differentiation of a type of fat tissue known as brown adipose tissue (BAT).

Published December 5 in the online edition of the journal Cell Metabolism, the study is the first to provide evidence of the relationship between Tyk2 and BAT. Previous studies by Larner and his team discovered that Tyk2 helps suppress the growth and metastasis of breast cancer, and now the current study suggests this same enzyme could help protect against and even reverse obesity.

The scientists were able to reverse obesity in mice that do not express Tyk2 by expressing a protein known as signal transducer and activator of transcription-3 (Stat3). Stat3 mediates the expression of a variety of genes that regulate a host of cellular processes. The researchers found that Stat3 formed a complex with a protein known as PR domain containing 16 (PRDM16) to restore the development of BAT and decrease obesity.

Continued:  http://www.sciencedaily.com/releases/2012/12/121205132433.htm

Lactating Tsetse Flies Models for Lactating Mammals?

ScienceDaily (Apr. 18, 2012) — An unprecedented study of intra-uterine lactation in the tsetse fly, just published in Biology of Reproduction's "Papers-in-Press," reveals that an enzyme found in the fly's milk functions similarly in mammals, making the tsetse a potential model for lipid metabolism during mammalian lactation.

Better yet, reduced levels of this enzyme led to poor health in offspring, leading the authors to suggest that targeting it could help decrease the tsetse population in Africa and so reduce the incidence of sleeping sickness. Tsetse flies are bloodsucking flies that inhabit much of subsaharan Africa. They are similar in size to a horsefly and breed along rivers and streams. A pathogenic species of parasite in the genus Trypanosoma can be taken in by the fly while taking a blood meal from an infected human or animal. Flies carrying the parasite can then transmit it to other humans or animals. The disease caused by the trypanosomes is known as sleeping sickness in humans and nagana in wild and domestic animals, including pigs, cattle, and horses.

Continued  http://www.sciencedaily.com/releases/2012/04/120418162302.htm