Thursday, February 6, 2014

Why would a biologist use BARD?

BARD is a tool for investigating bioassay data - data that chemical biologists and those in high-throughput screening labs already understand. But the data is useful to biologists working in traditional labs and bioinformaticians as well. Those scientists can use the data in BARD to learn more about their biological systems of interest as well, once they learn a bit about the concept of a chemical probe.

A chemical probe (or probe, for short) is a small molecule that has a well-defined effect on a biological system, canonically binding to and inhibiting or activating a single protein target. Many of the drugs we take could also be classified as probes (lipitor, aspirin, ibuprofin), but not all probes are drugs. A probe that meets a set of very strict criteria for bioavailability and safety can be put into clinical trials and (after much time, effort and money) be sold as a drug.

But probes are useful in research even if they are not used therapeutically. Good probes target a protein or pathway precisely - by treating a biological system with a probe we can specifically perturb one small piece of that system and observe how its behavior changes. Small molecules will sometimes be more tractable tools than genetic mechanisms like gene knockouts or shRNA knockdowns, as they can be easily controlled temporally than the former and can be more target-specific than the latter. For instance, the MEK inhibitor, PD035901, binds specifically to MEK and inhibits its ability to activate the MEK/ERK pathway. One can test whether a particular phenotype (like proliferation) is MEK-dependent by treating cells with the inhibitor and observing whether the phenotype occurs.

Chemical probes are incredibly useful tools and new probes are being developed on a regular basis as tools for interrogating the mechanics of the cell. The Molecular Libraries Program was an NIH-funded initiative to develop a series of these probes, using high-throughput screens. The data from these screens, including activity levels of the compounds and details about the assay (cell lines, reporter assay used, etc) are what is stored in the BARD database.

Although chemical probes are very useful, they are not the whole story of BARD.  BARD also contains the data for all of the small molecules that were tested as part of the path to identifying probes - and there are hundreds of thousands of these. Although these other molecules did not pass the same stringent requirements as the probes, the results of the experiments carried out on them can still shed light on biological pathways. Those results can be used to connect disparate biological processes, by finding compounds that are active in one process of interest and then searching for other processes in which the same compound is active.

BARD’s job is to make it easy for us to find the probes that are relevant to us - or to find probes that interact with our favorite protein or perturb our favorite biological pathway. Look for the next post, which will include a tutorial on how to find chemical probes that will push your research forward. While we work on that post, please check out some video walkthroughs of searching and investigating assay data using BARD, on the BARD YouTube channel.

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