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The biology of RNA interference has greatly facilitated analysis of loss-of-function phenotypes, but correlating these phenotypes with small-molecule inhibition profiles is not always straightforward. We examine the rationale of comparing RNA interference to pharmacological intervention in chemical biology.
There is a gap between the nanoscale level of molecular structure and the micron-sized level of cellular ultrastructure that is difficult to probe experimentally. New techniques and simulated images are revealing its secrets.
Animals time events on scales that span from microseconds to days. In contrast to the technologies devised by humans to keep track of time, biology has developed vastly different mechanisms for timing across these different scales.
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.