Automated assay workflow supports high-throughput target validation
Jan Stallen and Anais Legent are target discovery scientists at Galapagos, based in The Netherlands. Galapagos was founded in 1999 and has since built a pipeline that currently consists of 16 clinical, two pre-clinical, and 20 discovery programs that are advancing small molecule drug candidates against inflammatory diseases that were developed in-house. Stallen and Legent recently implemented a 4-plex cytokine assay in support of their inflammatory bowel disease program with an automated FLEXMAP 3D® workflow.
Tell us about your work at Galapagos.
Jan Stallen (JS): I’ve been at Galapagos for seven years; I currently manage the target discovery and validation team, but in the past, I managed the high throughput screening (HTS) group. I am also involved in the development and implementation of new technologies within the company and manage bioinformatics.
Anais Legent (AL): I started at Galapagos nearly three years ago and develop complex protein and cell-based assays that are used for target discovery screening.
What differentiates Galapagos from other clinical-stage biotechnology companies?
JS: We aim to develop disease modifying drugs that address the luminexcorp cause of the disease rather than just treating the symptoms. To accomplish this, we start screening in human primary cells and stay as close to the human as possible throughout the drug discovery process.
Galapagos relies on a patented HTS target discovery platform that uses an adenoviral shRNA library to target and silence the human drugable genome that results in the identification of disease-modifying targets.
Tell us about the co-culture assay workflow you developed.
JS: We developed a co-culture (gut epithelia + immune cells) assay to further screen new targets for immune modulation of Inflammatory Bowel Disease (IBD).
AL: I developed and optimized a 4-plex assay to further characterize hits from the functional screen that inhibited cytokine secretions, which elicited a high immune response.
We decided to start with a ready-made kit from a Luminex partner to save time and to minimize batch to batch variation. To increase throughput, I ported the assay from the commercially available 96-well format to a 384-well format and optimized incubation time, bead concentration, and wash conditions – because no kits for our cytokine targets were available in the 384 format at that time.
The consistency and reliability of the assay and instrument have enabled us to compare data across the entire screen with confidence.
How does the Luminex FLEXMAP 3D® fit into your drug discovery program?
JS: The FLEXMAP 3D meets our throughput needs and can take multiple analyte measurements at the same time. That’s why we adopted it for this project.
AL: Luminex instruments have intuitive interfaces that are user-friendly. We were up and running in a couple of weeks with no prior experience.
I understand your workflow is automated?
AL: Yes. We have a PAA KinEDx robotic arm that feeds the FLEXMAP 3D, and a custom made waste system. The automation reduces hands-on time and enables us to run plates continuously during the day and overnight, increasing throughput.
For this study, we ran approximately 40 multiplex assay plates that were generated from the supernatant of 160 96-well plates. We would not have been able to meet our timeline with the staff on hand if we would have run traditional ELISA assays.
What’s does the future hold for your group at Galapagos?
JS: We are developing more complex screens that provide us a more detailed understanding of disease modifying signaling pathways while also enabling us to select better hits. We will be expanding the adoption of the Luminex platform as it proved useful for the IBD project and empowers us to ask and answer more complex and biologically relevant questions.
Want more tips on how to automate your assay workflow?
Download the Automation of xMAP® Technology-Based Multiplex Assays white paper to learn more.
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