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Archive - Jan 27, 2012

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Probe of Mysterious Protein Involved in Diabetes, Cancer, and Aging

Like a magician employing sleight of hand, the protein mitoNEET -- a mysterious but important player in diabetes, cancer and aging -- draws the eye with a flurry of movement in one location while the subtle, more crucial action takes place somewhere else. Using a combination of laboratory experiments and computer modeling, scientists from Rice University and the University of California, San Diego (UCSD) have deciphered part of mitoNEET's movements to gain a better understanding of how it handles its potentially toxic payload of iron and sulfur. Their research was published online on January 23, 2012 in PNAS. "We scrutinize proteins with an unconventional approach," said Dr. José Onuchic, Rice's Harry C. and Olga K. Wiess Professor of Physics and Astronomy and co-director of the Center for Theoretical Biological Physics. "We use biophysics to probe biology rather than the other way around. Using computational theory, we find structures that are possible -- regardless of whether they've already been observed experimentally -- and we ask ourselves whether these structures might be biologically significant." Study co-leader Dr. Patricia Jennings, professor of chemistry and biochemistry at UCSD, who has collaborated with Dr. Onuchic for 15 years, said they save a great deal of time by using structural biophysics to guide their experiments on a wide variety of targets. For example, Dr. Jennings' laboratory determined less than five years ago that mitoNEET contained a novel folded structure. Since then, her lab has been using insights gained from static and dynamic snapshots of the protein to guide biological and biochemical studies. "I think people forget that proteins are machines with moving parts," said study lead author Elizabeth Baxter, a UCSD graduate student who works under the guidance of both Drs. Onuchic and Jennings.

Discovery May Aid Fight Againt Cholera

A team of biologists at the University of York in the UK has made an important advance in our understanding of the way cholera attacks the body. The discovery could help scientists target treatments for the globally significant intestinal disease which kills more than 100,000 people every year. The disease is caused by the bacterium Vibrio cholerae, which is able to colonize the intestine usually after consumption of contaminated water or food. Once infection is established, the bacterium secretes a toxin that causes watery diarrhea and ultimately death if not treated rapidly. Colonization of the intestine is difficult for incoming bacteria as they have to be highly competitive to gain a foothold among the trillions of other bacteria already present in situ. Scientists at York, led by Dr Gavin Thomas in the University’s Department of Biology, have investigated one of the important routes that V. cholera takes to gain this foothold. To be able to grow in the intestine, the bacterium harvests and then eats a sugar, called sialic acid, that is present on the surface of our gut cells. Collaborators of the York group at the University of Delaware, USA, led by Professor Fidelma Boyd, had shown previously that eating sialic acid was important for the survival of V. cholerae in animal models, but the mechanism by which the bacteria recognize and take up the sialic was unknown. The York research demonstrates that the pathogen uses a particular kind of transporter called a TRAP transporter to recognize sialic acid and take it up into the bacterial cell. The transporter has particular properties that are suited to scavenging the small amount of available sialic acid. The research also provided some important basic information about how TRAP transporters work in general. Dr.

New Vaccine Approach to Cancer Reported

Scientists at Trinity College Dublin (TCD), Ireland, have developed a new vaccine to treat cancer at the pre-clinical level. The research team led by Professor Kingston Mills, Professor of Experimental Immunology at TCD discovered a new approach for treating the disease based on manipulating the immune response to malignant tumors. The discovery has been patented and there are plans to develop the vaccine for clinical use for cancer patients. The first cancer vaccine Sipuleucel-T (Provenge™) was licensed last year for use in prostate cancer patients unresponsive to hormone treatment. Unfortunately, this cell-based vaccine only improves patient survival by an average of 4.1 months. Vaccines for infectious diseases are highly effective at generating immune responses that prevent infection with bacteria or viruses. The immune system can also protect us against tumors and, in theory, a vaccine approach should be effective against cancer. In practice, this has proven very difficult because, unlike infectious diseases, tumors are derived from normal human cells, and are not made up of foreign substances or antigens capable of triggering an immune response. The tumors instead produce molecules that suppress the efficacy of the immune system. They generate regulatory cells that inhibit the immune response that could potentially clear the tumors. Professor Mills' group has developed a novel vaccine and immunotherapeutic approach that can overcome these obstacles and has the potential to significantly improve on existing technologies. The therapy is based on a combination of molecules that manipulates the immune response to curb the regulatory arm while enhancing the protective arm, allowing the induction of specialist white blood cells called killer T cells to target and eliminate the tumors.