Miniaturisation on a Large Scale: Optimising High-Throughput Screening at a Large Academic Facility

Written by Bioscribe on October 10, 2018

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How does a large academic screening center deal with the extremely high throughput demands of its in-house chemical library of more than 450,000 compounds?

The Small Molecule Screening Facility (SMSF) at the University of Wisconsin Madison’s Carbone Cancer Center takes advantage of the miniaturisation and optimisation enabled by Labcyte Echo acoustic technology to provide speedy, accurate, and cost-efficient services to academic and industry clients worldwide.

In an upcoming live webinar hosted by Drug Target Review on 30 October, “Cell-based and biochemical high-throughput screening in 1536-well plates,” Core Facility Manager, Gene E. Ananiev, Ph.D., will explain just how he does it. He will be joined by Carl Peters, Ph.D., Senior Application Scientist with BMG LABTECH, and Iain Russell, Ph.D., Senior Product Manager with Labcyte.

Dr. Ananiev will present two specific examples of the system in action: a screen for protein-protein interactions, and a cell-based luciferase reporter assay.

The first project was undertaken in an attempt to address the urgent need for novel classes of antibiotics capable of overcoming existing resistance mechanisms. It focused on one potential antibiotic target, the bacterial single-stranded DNA binding protein (SSB), which serves as a hub for DNA repair, recombination, and replication.

As a first step toward implementing a strategy of inhibiting protein-protein interactions at the terminal tail of SSB, Ananiev’s team developed orthogonal high-throughput screening assays to identify small-molecule inhibitors of the Klebsiella pneumonia SSB-PriA interaction. As reported in this SLAS Discovery publication, hits were identified from an initial screen of 72,474 compounds, nine potent and selective inhibitors were found to produce concentration-response curves with IC50 values of <40 μM, and two compounds were observed to directly bind to PriA, demonstrating the success of this screen strategy.

“Using a miniaturised AlphaScreen, we were able to drastically reduce cost and increase throughput for protein-protein interaction high throughput screening,” he says.

For cell-based HTS, he will discuss screening for activators of gene-expression using iPSC derived, neural progenitor cells, engineered with a Nano-Luciferase reporter using the CRISPR/Cas9 genome editing method.

“We confirmed that luciferase activities faithfully report FMR1 gene expression levels and showed that neural progenitor cells derived from this line could be optimised for high-throughput screening,” Ananiev says.

» REGISTER HERE to join us, 30 October, 16:00 GMT

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