Web edition: October 20, 2009
Building from the bottom up with the art of synthetic biology
Cells suck. That’s the dirty little secret of synthetic biology, according to Zack Booth Simpson, who dropped out of high school to develop video games, do art and now is also doing science as a research fellow at the Center for Systems and Synthetic Biology at the University of Texas at Austin. (He supports himself with his art; the science he does “for fun.”) Simpson wants to reengineer a new world, built the biological way—from the bottom up.
“If whales and trees can be built from seeds, why can’t submarines and cell phone towers be built that way?” said Simpson at a morning session October 19.
Biological structures, such as a bird wing, will self-repair when damaged, responding to the injury and the environment. The absence of these responsive properties makes things built by humans brittle, bustable, fallible. But biological entities—cells, for example—have a continuous interaction with their environment.
“Life is a computation,” said Simpson. “There’s a constant calculation. You can kind of define death as when this computation no longer takes place.”
Synthetic biology—engineering biological devices and systems that nature may not have gotten around to—and nanotechnology are the fields that offer promise for Simpson’s dream. Yet he is the first to admit their shortcomings.
“Even if we had a functional nano toolkit right now,” “I would not be able to build you a whale,” he said.
For one thing, amplifying from a tiny seed to a larger structure is not so simple. And there's also the matter of cells sucking. Trying to engineer living things is like working with a computer that does what is is told half the time and half the time runs the programs it wants to run, said Simpson.
"Cells have a mind of their own," said Simpson. "They do not want to do what you want them to do, so evolution always wins."
Rather than working with cells, Simpson and his collaborators are using nucleic acids—the stuff of genetic material—and imposing the circuitry of the world of electronics. Nucleic acids interact in chemically predictable ways but don't have minds of their own. This electrical engineering approach to biological construction, dubbed nucleic acid amorphous computing, holds promise for getting from seed to submarine, said Simpson.
“Learning to write programs is to understand life,” he said.
See more at Simpson’s website. —Rachel Ehrenberg
PTSD studies seek ways to ‘inoculate’ soldiers
Receiving bad news from home is one of the highest stressors of the battlefield, second only to hostile incoming fire, according to preliminary data presented in a morning session October 20.
“Not only do they have the stressors in the war zone, but they are constantly bombarded by messages from home,” said Michael Telch, (cq)director of the Laboratory for the Study of Anxiety Disorders at the University of Texas at Austin. “They are flooded with the Internet…. You wouldn’t believe the stories I’ve heard of women moving in boyfriends, then the boyfriends drove the soldiers’ cars, used their credit cards and all sorts of horrific things.”
The weight of various aspects of war emerged from data gathered in stress logs kept by more than 150 soldiers from Fort Hood who were deployed as part of Operation Iraqi Freedom. Keeping stress logs is one aspect of a project that aims to untangle what risk factors predispose soldiers to post-traumatic stress disorder, which can leave those who have experienced traumatic events with persistent emotional and physiological and psychological problems.
Diagnosing PTSD in veterans has been controversial, in part because most studies are retrospective—they try to extrapolate by looking back—and they often rely on self-reported questionnaires. Several factors, including a desire (unconscious or not) to suppress the effect of traumatizing events, can skew self-reported data.
Telch and his colleagues are taking a new approach to examining PTSD: evaluating soldiers before they are sent to Iraq, throughout their deployment and re-assessing them when they get home. The researchers are looking for correlations with factors that include genetics, data gathered from brain imaging and psychological history.
Preliminary results suggest that a history of psychological problems, substance abuse and a sensitivity to anxiety all may predispose soldiers to PTSD, reported Telch. The hope is the research will lead to means to “inoculate” at-risk soldiers before they are deployed — for example, by getting them used to experiencing the equivalent of a panic attack so they are less fearful of it on the battlefield.
Should some soldiers not be deployed at all? “It seems to make sense to reduce the vulnerability in the face of high stress, rather than to screen them out,” Telch said.—Rachel Ehrenberg
University of Texas at Austin biologist Hans Hofmann and his research team went to eastern Africa to study African cichlids, a family of fish that has split off into thousands of species relatively recently. Several species show markedly different social behavior patterns—for instance, some are monogamous, and some polygamous.Hofmann and his students dissected four different species, two of each mating type, and found that the monogamous species have larger forebrains.
“If you’re a defender of family values, you’d say, Yeah! This makes sense!” Hofmann said in Austin, Texas at the annual Council for the Advancement of Science Writing symposium. But he pointed out that he could craft a convincing story to justify polygamous fish having larger brains, too. “That is the problem of evolution studies—it’s all just-so stories.”More concretely, the researchers found 1,200 genes that were correlated with either monogamy or polygamy. Hofmann thinks it’s likely that these genes have counterparts in a wide variety of vertebrate species, including humans. Other systems that regulate behavior, like the system that releases and absorbs a neurotransmitter linked to romantic love and mother-baby bonding, have been shown to be conserved across species.
“There’s no reason to assume if all other vertebrates use these pathways, that humans don’t,” he said.But when asked if humans are monogamous or polygamous, he said it’s a “nonsensical question.”
“There’s pretty good evidence, if you look at the structure of our genitalia, that we’re probably polyandrous,” he said. “Females are, evolutionarily speaking, promiscuous, and the males are just scrambling to get a piece of the pie.” —Lisa Grossman
Reproduction on the brain
Gore studies the hypothalamus, a region of the brain where, she says, “the brain and hormones meet.” It plays a critical role in controlling sexual development and reproduction in both women and men.
“We aren’t trying to ‘cure’ menopause,” Gore said, “but to understand how hypothalamic changes contribute to the process.”
Ovulation and the making of new sperm are both regulated by a cluster of 800 neurons in the hypothalamus that produce GnRH, short for gonadotropin-releasing hormone. In adults, these GnRH neurons send out pulses of the hormone every hour, which trigger the release of other reproductive hormones (luteinizing and follicle stimulating hormones) from the pituitary gland. These neurons are also involved in early development in the embryo and, after laying dormant during childhood, in the onset of puberty, when they increase their output of hormone between 20- and 50-fold, Gore said.
While the main part of the GnRH neurons, the cell bodies, are located in the hypothalamus, many of the neurons’ long fibrous arms end in another area of the brain called the median eminence — a little loop at the base of the brain that sits just below the hypothalamus. Gore’s studies of the median eminence in aging rats show profound differences and “big changes in the structure and organization,” she and her colleagues report in a study soon to appear in Endocrinology. These changes appear to affect the ability of the hormone to reach the pituitary gland.
“We know the older animals can make the GnRH and transport it, but it seems like it’s kind of getting stuck,” she said. Its release is no longer being coordinated in the hourly pulses, and so the hormones don’t get into the body. And that may interfere with ovulation in females and spermatogenesis in males.
She hopes the research may provide new insight into infertility and premature menopause. —Eva Emerson