Automation and High-Throughput Technologies

An Approach to Neglected Disease through Automation, Collaboration and High Value Chemical Libraries.

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  Mitchell Hull

  Principal Investigator, Head of Automation
  California Institute for Biomedical Research

Traditionally, the format of high throughput screens set large compound libraries against single targets, usually represented by simple biochemical, reporter gene or viability assays. The chemical libraries, were often derived by combinatorial chemistry methods and generally had unknown value or bioactivity. To maximize this approach, programs frequently focused on target families, which could be screened with the same format. This methodology generated large amounts of data very quickly, but it was not always proportionately successful. This approach has waned and there is a shifting trend toward disease-based programs, which emphasize target diversity and multiple biologically relevant assays screened against smaller chemical libraries. Traditional screening is still relevant and continues at Calibr. However, we have embraced the later approach, specifically in our mission to address neglected disease. To improve the chemical matter discovered from smaller screens, we created a library of high value pharmacophores with known or suggested bioactivities. Implementing the most relevant bioassays for neglected diseases can be challenging in a standard lab. Not only do they require high biosafety levels, they may require atypical facilities and skill-sets such as insectariums and continuous culturing of whole organisms. To expand assay diversity, we reached out to other organizations and academic labs to collaborate on screens, which would supplement our own programs. Through these relationships, we expanded the assay diversity of our programs and the collaborator gained access to our library and our own capabilities, assistance and expertise. We will describe the challenges, solutions and successes of this approach, specifically in providing assay support, compound management and data curation to these collaborators.