Tips on how to build a better home for biological parts

Researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech have compiled a series of guidelines that should help researchers in their efforts to design, develop and manage next-generation databases of biological parts. The stakes are high: the concept of biological parts is essential if methods developed in other fields of engineering are to be applied to biology. If successful, this approach will result in significant productivity gains for the biotechnology industry. The findings of the research, published in the Public Library of Science's open-access journal PLoS One, arose from a systematic analysis of the Registry of Standard Biological Parts, the most well developed collection of biological parts currently available to the synthetic biology research community.

Jean Peccoud, associate professor at the Virginia Bioinformatics Institute, remarked: "Our research group is very interested in providing the wider research community with design automation tools that will facilitate the engineering of biological systems. We needed to take a close look at the Registry of Standard Biological Parts in order to understand how GenoCAD™, the platform we are developing to build and verify complex genetic constructs, should interface with this important community resource. In this process, we came to understand that repositories of biological parts represent a new generation of bioinformatics databases that pose a number of original and very interesting challenges." He added: "We believe that articulating the issues associated with these resources will help improve existing databases of biological parts. It will also assist in the development of new collections of parts for specialized applications such as bioenergy or biodefense."

The Registry of Standard Biological Parts is a publicly available resource and the focal point of the annual International Genetically Engineered Machine (iGEM) competition. iGEM undergraduate students engineer novel biological systems starting from BioBricks, the parts documented in the Registry of Standard Biological Parts. The BioBrick is an emerging standard for DNA fragments that facilitates the assembly of biological parts into more complex devices and systems by using a standardized fabrication process. The entire collection of parts associated with the Registry is distributed to all teams enrolled in the iGEM competition. The iGEM participants are expected to return the designs they made to the Registry at the end of the competition.

The new study by VBI researchers not only examined the information content of the Registry database but also the collection of publicly available DNA sequences or clones (BioBricks) that are used to make the biological devices and systems. The analysis of the Registry database and the associated DNA clones identified several key needs where improvements could be made. These included the following: (a) to distinguish basic parts and composite parts that can be broken down into smaller parts; (b) to set curation standards to document the sequences of basic parts by associating them with entries in bioinformatic or bibliographic databases; (c) to define and implement quality control standards that ensure the integrity of DNA clones; and (d) to provide editorial policies that could help build registries of biological parts with high-value and high-quality content.

Peccoud concluded: "The Registry of Standard Biological Parts has been a pioneering experiment for the synthetic biology community and lessons should be learned to improve this resource and design the next-generation registries of biological parts. This bottom-up approach to biology raises a number of challenging theoretical questions. Defining what is a biological part, for example, remains a problem that the entire synthetic biology community needs to solve. In this respect, recent initiatives led by the BioBrick foundation and others to organize forums that define technical standards for biological parts appear to be very timely and laudable."

###

‡ A complete description of the findings and recommendations of the analysis are available in the publication: "Targeted development of registries of biological parts", July 16, 2008 edition of PLoS One: http://www.plosone.org/doi/pone.0002671.

About VBI

The Virginia Bioinformatics Institute (VBI) at Virginia Tech (www.vbi.vt.edu) has a research platform centered on understanding the "disease triangle" of host-pathogen-environment interactions in plants, humans and other animals. By successfully channeling innovation into transdisciplinary approaches that combine information technology and biology, researchers at VBI are addressing some of today's key challenges in the biomedical, environmental and plant sciences.

D-cycloserine may improve behavioral therapy treatment for anxiety

Anxiety is a normal human response to stress, but in some, it can develop into a disabling disorder of excessive and irrational fears, such as obsessive-compulsive disorder, panic disorder, or posttraumatic stress disorder. Effective treatments are available and can involve either behavioral therapy or medications. Although "it makes intuitive sense that combining these two treatments would result in even better results," David Tolin, Ph.D. notes that has unfortunately not yet been the case and the majority of the evidence suggests that combined therapy is no more effective than behavior therapy alone, and in some cases can even be less effective. However, Dr. Tolin is one of the three authors on a meta-analysis scheduled for publication on June 15th in Biological Psychiatry, in which they evaluated a potentially important new treatment paradigm for anxiety.

Dr. Tolin explains the impetus behind their analysis: "Recently, several researchers have tried a radically different approach: instead of just throwing two effective monotherapies at the problem, they have instead looked at medications that specifically target the biological mechanisms that make psychotherapy work in the first place." John H. Krystal, M.D., Editor of Biological Psychiatry and another of the study's authors, adds that "there has now been a sufficient amount of research in this area to take a step back to look at the basic research conducted in animals and the initial clinical trials." This research effort has involved the addition of D-cycloserine, an old drug long approved by the U.S. Food and Drug Administration for the treatment of tuberculosis, to exposure-based fear treatment in animals and humans. The meta-analysis, a pooling of the published literature on this approach, provides evidence that D-cycloserine enhances the learning process in the brain, indicating that, unlike many other medications, it may improve the effectiveness of behavioral therapy.

There is a caveat, however, as the authors also discovered that tolerance may develop to this effect. Dr. Krystal comments that, if so, "it may be best used before therapy sessions to 'warm up the brain' and make it more responsive to the treatment sessions rather than as a daily treatment."

Dr. Tolin makes an additional, important observation regarding this line of work: "Another very exciting aspect of this work is that it's one of the few really good examples of translational research in psychiatry: taking basic science from the laboratory, in this case animal studies, and translating that research into useful interventions for humans." Although additional research is clearly necessitated, this confirmation of the effectiveness of D-cycloserine is a positive step forward in improving treatments for individuals suffering with anxiety disorders.

Men and women may need different diets: University of New South Wales research

Diet can strongly influence how long you live and your reproductive success, but now scientists have discovered that what works for males can be very different for females.

In the first study of its kind, the researchers have shown that gender plays a major role in determining which diet is better suited to promoting longer life or better reproductive success.

In the evolutionary "battle of the sexes", traits that benefit males are costly when expressed in females and vice versa. This conflict may have implications for human diet, aging and reproduction, says a team of scientists from UNSW, the University of Sydney and Massey University.

"When it comes to choosing the right diet, we need to look more closely to the individual, their sex and their reproductive stage in life," says Associate Professor Rob Brooks, Director of the Evolution and Ecology Research Centre at the University of New South Wales. "It may be, for example, that women in their child-bearing years need a different diet to those who are post-menopausal.

"It also underlines the important lesson that what we want to eat or, if you like, what we're programmed to eat, is not necessarily best for us." The researchers are conducting long-term studies on Australian black field crickets and have discovered that the lifespan of both males and females is maximised on high-carbohydrate, low-protein diets, they say in the latest issue of Current Biology.

But reproductive success differs dramatically between the sexes when the carbohydrate-protein balance is changed: males live longest and have the greatest reproductive success with a diet that favours carbohydrates to protein by eight-to-one, whereas females have greatest success when the ratio is just one-to-one. Given a choice, however, females eat only a small amount more protein than males. The shared ability to sense and choose food dooms both males and females to eat a diet that is a compromise between what is best for each sex.

"Male and female crickets maximise their fitness on different diets," says UNSW's Dr Alexei Maklakov, the study's lead author. "Despite that, the dietary preferences of the sexes are very similar. Instead of selecting foods in a sex-specific manner, males and females select 'intermediate' diets that are less than optimal for both sexes.

The researchers believe the sexes share most of their genes and this fact can constrain the evolution of sex differences in traits such as diet choice, because many of the same genes are likely to be responsible for trait expression in both sexes.

Significance for humans – "Men and women invest differently in reproduction, a difference that is even more marked than that between male and female crickets," says Rob Brooks. "Think of the tremendous amounts of energy and protein required of a mother in carrying a baby to term and breastfeeding. We also know that men and women need to eat different diets - think of the careful attention we pay to what expectant mothers eat.

"What men and women need to eat might be more dramatically different than we had realised. However, men and women eat very similar diets and our results suggest that our tastes and food preferences could be a shared compromise, as they are in crickets."