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Science Friday: BigBirdasaurus | Immune proteins spread a net to trap bacteria | T-cell Vaccines Could Treat Elusive Diseases

All dinosaurs may have had feathers

    Early dinosaurs probably looked a lot more like Big Bird than scientists once suspected. A newly discovered, nearly complete fossilized skeleton hints that all dinosaurs may have sported feathers.

    “It suggests that the ancestor of all dinosaurs might have been a feathered animal,” says study author Mark Norell, a paleontologist at the American Museum of Natural History in New York.

    Researchers have found feathered dinosaurs before, but this one is more distantly related to birds than any previously discovered. Called Sciurumimus albersdoerferi, it belongs to a group of massive dinosaurs called megalosaurs that had sharp teeth, claws and a heavy-duty frame. The specimen — a youngster that lived about 150 million years ago — is only 70 centimeters long, but it could have grown up to 10 meters, about the length of a school bus.


Immune proteins spread a net to trap bacteria

    A “natural antibiotic” protects the body against bacteria by tangling them in a net, not poking holes in them, a team led by UC Davis Health System researchers has found.

    It’s an entirely new mechanism of action for defensins, an important group of molecules known to bolster the body’s defenses, and provides important clues to inflammatory bowel diseases, especially Crohn’s disease. The work is published tomorrow, June 22 in the journal Science.

    “During the past 25 years, researchers have learned a lot about the biological function of defensins, but the role of HD6, a particular molecule that is highly expressed in the intestines, was a mystery,” said Charles Bevins, professor of microbiology and immunology at UC Davis.

    [Image: electron micrograph shows bacteria caught in a net of HD6 defensins].

    First author of the paper is Bevins’ former graduate student Hiutung Chu, now a fellow at the Caltech, who spent nine years puzzling it out. Bevins is co-senior author of the paper along with his UC Davis colleague Professor Andreas Bäumler, an expert in bacterial pathogenesis; UCLA Emeritus Professor Robert I. Lehrer, whose laboratory was the first to discover defensins in the early 1980s; and Professor Wuyuan Lu, a synthetic protein chemist from the University of Maryland School of Medicine whose work provided clues to HD6’s subtle and unique properties.

    About the protein HD6

    Defensins are a family of structurally related, small peptides with antibiotic activity found throughout nature in plants and animals. Humans make six different alpha-defensins. Two of these, HD5 and HD6, are secreted by Paneth cells, specialized secretory cells located within the folds of the small intestinal lining. HD5 has well-known antibacterial properties while the function of HD6 had been unknown. The defensin-rich secretions of Paneth cells work in conjunction with nearby intestinal stem cells to maintain micro flora balance and renew intestinal cellular surfaces.

    Other alpha-defensins kill pathogens by poking holes in the microbial membrane, but Chu’s early research studies repeatedly showed that HD6 did not kill bacteria in culture.

    Two frustrating years into the project, Bevins and Chu recognized two crucial pieces of information. The first was that whenever HD6 was added to suspensions of either bacteria or fungi, a white haze, or precipitate, formed in the solution. The second was that early studies conducted in collaboration with Bäumler had shown that while HD6 did not kill the bacterial pathogen Salmonella, it did protect transgenic mice from an otherwise lethal infection.


T-cell Vaccines Could Treat Elusive Diseases

    For some infectious diseases, traditional vaccines just don't cut it. Microbes that hide inside human cells and cause chronic illness aren't stymied by the antibody response generated by the kind of vaccine available at the doctor's office. T-cell vaccines, which activate a different type of immune response, could, in theory, better prevent or control such chronic infections, but so far nobody has been successful at transitioning T-cell vaccines from the lab bench to the clinic.

    A Cambridge, Massachusetts, biotech company called Genocea thinks its high-throughput method could change that. The company will begin its first clinical trial later this year, when its experimental herpes vaccine will be the first test of its claims.

    All existing vaccines rouse the body into creating antibodies that attach to the surface of infecting microbes and flag them for destruction. But pathogens that live inside our cells, such as the viruses, bacteria, and other microbes that cause AIDS, malaria, herpes, and chlamydia, can evade this surveillance. "In order to deal with those types of pathogens, oftentimes we have to stimulate what we call cellular immunity. Unlike antibody immunity, which recognizes pathogens directly, cellular immunity has to recognize the infected cell and get rid of your own infected cells," says Darren Higgins, a biologist at Harvard Medical School who studies the interaction between hosts and pathogens and is a cofounder of Genocea.

    But activating cellular immunity—and the family of infection-fighting cells known as T cells that drive it—is challenging. The trial-and-error method used to develop antibody-based vaccines has not worked for T-cell vaccines. Despite years of academic and industry work, and even clinical trials, there are no T-cell vaccines for infectious disease on the market. "We don't know all of the rules yet if it's possible to make a T-cell vaccine, [nor] how effective it would be," says Robert Brunham, a physician-scientist at the University of British Columbia in Vancouver who is working on developing a chlamydia T-cell vaccine.