Commentary in 2009

Intrinsically disordered proteins (IDPs) are subject to ubiquitin-independent degradation, a default and passive process. We describe here a model wherein a group of 'nanny' proteins function to protect newly synthesized IDPs from degradation by default, thereby insuring their maturation into important regulatory molecules.

In their native environments, proteins perform their biological roles in highly concentrated viscous solutions and in complex networks with numerous partners. Yet for many years, the normal practice has been to purify a protein of interest in order to characterize its structural and functional properties. In this Commentary, we discuss how protein scientists are now tackling the theoretical and methodological challenges of studying proteins in their physiological context.

Phenotypic diversity exists even within isogenic populations of cells. Such nongenetic individuality may have wide implications for our understanding of many biological processes. The field of study concerned with the investigation of nongenetic individuality, also known as the 'biology of noise', is ripe with exciting scientific opportunities and challenges.

Annotations of enzyme function provide critical starting points for generating and testing biological hypotheses, but the quality of functional annotations is hindered by uncertain assignments for uncharacterized sequences and by the relative sparseness of validated experimental data. Given the relentless increase in genomic data, new thinking and validation methods are urgently needed to provide high confidence in enzyme functional assignments.

The scope of enzymology has expanded rapidly over the last century, from an early focus on the chemical and catalytic mechanisms of individual enzymes to more recent efforts to understand enzyme action in the context of dynamic, functional biological systems consisting of many interacting enzymes and proteins. Continuing progress in probing the link between molecular structure and function now promises to pave the way for a deeper understanding of the evolution and behavior of the complex biological systems that govern cellular behavior.

Protein improvement strategies today involve widely varying combinations of rational design with random mutagenesis and screening. To make further progress—defined as making subsequent protein engineering problems easier to solve—protein engineers must critically compare these strategies and eliminate less effective ones.

Understanding the structure and function of carbohydrates remains a key challenge for chemical biologists. Developments in carbohydrate synthesis and analysis together with the advent of high-throughput methods such as carbohydrate microarrays have helped shed light on the function of glycoconjugates. Similarly, consortia have provided technology platforms and focus to a burgeoning field. Now, recruitment of scientists from related fields and further integration of chemistry and biology to achieve technical goals are needed for rapid advancements.

Chemical biology is beginning to enhance our understanding of diverse cellular processes in plants, including endomembrane trafficking, hormone transport and cell wall biosynthesis. To reach its potential requires the development of a community-wide infrastructure of technology and expertise. We present some of the opportunities and challenges in this emerging branch of plant biology and offer some suggestions for enhancing the approach to the benefit of the community at large.

Receptor heteromers constitute a new area of research that is reshaping our thinking about biochemistry, cell biology, pharmacology and drug discovery. In this commentary, we recommend clear definitions that should facilitate both information exchange and research on this growing class of transmembrane signal transduction units and their complex properties. We also consider research questions underlying the proposed nomenclature, with recommendations for receptor heteromer identification in native tissues and their use as targets for drug development.

Autofluorescent proteins have become indispensable in our quest to visualize molecular events in living cells. Further progress in the visualization and quantification of all biochemical activities of the cell will require the introduction of additional and complementary methods for sensing and probing biomolecules. Here I highlight some of the areas where the development of new probes and labeling methods is eagerly awaited and where chemical biologists could make important contributions.