Claudins

How so? The emergence of chemical biology in universities and medical schools reflects a transition towards the integration of small molecule synthesis, small molecule screens and informatics with the goal of illuminating principles that underlie biology and disease. This is not drug discovery, but the resulting concepts and technologies can be incorporated by the pharmaceutical industry into their drug discovery process. For example, such efforts have already identified many previously unrecognized therapeutic targets whose activities can be modulated by small molecules — information that can be exploited by the pharmaceutical industry. Will the 'gulf' between chemists and biologists, to which Arthur Kornberg famously referred, interfere with these ambitions? Possibly, as so much still needs to be accomplished and the gulf still exists. To advance our understanding of disease biology, we need chemists to populate 'chemical descriptor space' beyond that occupied traditionally by drugs, yielding diverse small molecules that disrupt protein–protein interactions, enhance binding specificity, and modulate targets previously thought to be 'non-druggable'. We need to unleash the awesome creativity of biologists in a disease-relevant and small molecule-based context. But creating a social structure where chemists are eager to use their skills to follow-up on biologists' discoveries is vitally important. The participation of chemists prior to the start of the screening process develops an environment in which the chemists are excited to participate with biologists in efforts to optimize the properties of the hits discovered in screens, thereby moving them towards more effective disease probes or even drugs. Any other relevant sociologic issues? I think so. For example, there are operational and cultural issues that distinguish academic research from research performed in the pharma industry. Operationally, academic biologists tend to tinker with candidate assays, a trial-and-error process that requires ready, hands-on access to a minimal set of screening equipment and expertise. Much of the work is performed in a pilot mode, rather than the large-scale but more limited-in-scope mode often used in industry. Culturally, academic biologists are more apt to create new screening paradigms than to adopt those used in drug discovery in industry. Examples include the use of matrix screening datasets to create signatures of cell states, and the use of state-switching assays. Academic screening centers differ from their industrial counterparts. Is this another example of 'big' biology? Not really. Biology in all sizes benefits from the tools and concepts being developed by chemical biology, just as all sizes of …