Commentary

Live samples are intrinsically highly dynamic, yet techniques to monitor these complex environments usually reflect snapshots, thus making time-lapse imaging necessary to explore temporal progression of biological functions. Recent results indicate that exploiting some basic features of fluorescent protein maturation, such as green-to-red maturation of engineered proteins, should allow probing of temporally regulated information.

The mid-nineteenth century saw the development of a radical new direction in chemistry: instead of simply analyzing existing molecules, chemists began to synthesize them—including molecules that did not exist in nature. The combination of this new synthetic approach with more traditional analytical approaches revolutionized chemistry, leading to a deep understanding of the fundamental principles of chemical structure and reactivity and to the emergence of the modern pharmaceutical and chemical industries. The history of synthetic chemistry offers a possible roadmap for the development and impact of synthetic biology, a nascent field in which the goal is to build novel biological systems.

Publications reporting results of small-molecule screens are becoming more common as academic researchers increasingly make use of high-throughput screening (HTS) facilities. However, no standards have been formally established for reporting small-molecule screening data, and often key information important for the evaluation and interpretation of results is omitted in published HTS protocols. Here, we propose concise guidelines for reporting small-molecule HTS data.

The chemical scaffolds from which screening libraries are built have strong influence on the libraries' utility for screening campaigns. Here we present analysis of the scaffold composition of several types of commercially available screening collections and compare those compositions to those of drugs and drug candidates.

The increasing availability of data related to genes, proteins and their modulation by small molecules has provided a vast amount of biological information leading to the emergence of systems biology and the broad use of simulation tools for data analysis. However, there is a critical need to develop cheminformatics tools that can integrate chemical knowledge with these biological databases and simulation approaches, with the goal of creating systems chemical biology.

Biosynthetic pathways for secondary metabolites usually make many products, not just one. In this Commentary, we consider why molecular promiscuity might be an evolutionarily advantageous feature of these pathways.

Project ownership is an essential but sometimes overlooked ingredient for a successful undergraduate research experience. We have embarked on an experiment in undergraduate education that targets isolation of microbes from rainforest plants and characterization of natural products as objectives for discovery-based undergraduate research.

Mixtures of interacting compounds produced by plants may provide important combination therapies that simultaneously affect multiple pharmacological targets and provide clinical efficacy beyond the reach of single compound–based drugs. Developing innovative scientific methods for discovery, validation, characterization and standardization of these multicomponent botanical therapeutics is essential to their acceptance into mainstream medicine.

African Americans, Hispanics and Native Americans are significantly underrepresented in chemistry and related sciences. An innovative approach based on course revision, peer support, precollege training and strong mentoring offers promise for engaging and retaining more underrepresented minority students and more members of the majority population in these fields.

Drug screening in the immediate term will be best accomplished by early use of primary cells in which the target of the screen is a network of proteins measured in populations of single cells.

The broad range of techniques used in chemical biology presents many challenges in reporting, translating and implementing experimental knowledge. By taking advantage of some readily available solutions and instituting some new approaches, it should be possible to more effectively disseminate technological advances.

Model systems have evolved with the times, making use of modern biological methods and incorporating biological complexity. This evolution has increased the relevance of models as tools for studying biology.

As cellular machines and processes that regulate the flow of genomic information have come into sharper focus, a new level of chemical control has become possible. The scope of such chemical intervention extends from the mechanistic dissection of biochemical processes in living cells to the targeted control of gene networks and cell fate.

RNA interference provides powerful tools for controlling gene expression in cultured cells. Whether RNAi will provide similarly powerful drugs is unknown. Lessons from development of antisense oligonucleotide drugs may provide some clues.

By building on the successes of the past and leveraging both innovative technologies and predictive knowledge, scientists can develop smarter ways to create a molecular armamentarium of chemical and biological medicines.

Translational research in academia is extending beyond the traditional involvement in clinical trials to the early phases of the drug discovery process. Examples of successful academic-industrial partnerships illustrate the ways in which they can enable the discovery of new medicines.

Biological membranes are two-dimensional mixtures of an enormous number of different components. Modeling cell membranes as simple bilayer mixtures reveals rich phase behavior, but how can we use the observed phase behavior to understand the real membranes?

Physical chemistry explains the principles of self-organization of lipids into bilayers that form the matrix of biological membranes, and continuum theory of membrane energetics is successful in explaining many biological processes. With increasing sophistication of investigative tools, there is now a growing appreciation for lipid diversity and for the role of individual lipids and specific lipid-protein interactions in membrane structure and function.

Bioinorganic chemistry remains a vibrant discipline at the interface of chemistry and the biological sciences. Metal ions function in numerous metalloenzymes, are incorporated into pharmaceuticals and imaging agents, and inspire the synthesis of catalysts used to achieve many chemical transformations.

Chemical biology graduate programs that are jointly organized by chemistry and life science departments can offer a stimulating 'bicultural' training environment for students from diverse backgrounds. However, communication, flexibility and responsiveness are crucial for effectively structuring such programs.