Exploring New Boundaries in Humanized Drug Discovery
DiscoveryBioMed, Inc., supplies products and services to help the drug discovery community improve attrition rates and pinpoint compounds that are high-value clinical candidates. Since its founding in 2007 by physiologist Dr. Erik Schwiebert, this Birmingham, Alabama based company’s novel ‘Humanized Drug Discovery’ approach identifies and develops highly relevant diseased and normal human cell models, and integrates them along every step in the drug discovery critical path. The company has expertise in several areas of custom cell engineering and cell-based drug discovery, particularly in human renal, respiratory, and metabolic systems.
The first thing that visitors to the DiscoveryBioMed laboratory notice is the multitude of BioTek products — it’s clear that the company places a high degree of trust in BioTek’s technologies. John Streiff, Ph.D., Chief Chemoinformatics Officer at DiscoveryBioMed, notes that at the company’s founding, the Synergy™ HT Multi-Mode Reader was used for drug screenings and assays. “After using our Synergy HT for ten years and counting, I know it inside and out, and the difference between this and other readers is amazing,” he says. A Synergy Neo Multi-Mode Reader provides ultra-fast measurements in a variety of detection modes to facilitate drug screening and other activities in their R&D and contract research divisions, and when it comes to low-volume nucleic acid quantitation, they depend on the streamlined efficiency of the Take3™ Micro-Volume Plate.
One of the most frequently used instruments in DiscoveryBioMed’s lab is the Cytation™ 5 Cell Imaging Multi-Mode Reader. In fact, the lab owns two Cytation 5 instruments. One is used as a standalone imager and reader, while the other is integrated into an automated live cell analysis system along with the BioSpa™ 8 Automated Incubator and MultiFlo™ FX Multi-Mode Dispenser. Deborah Mai, Ph.D. is DiscoveryBioMed’s Chief Biological Officer, and relies on both Cytations when working with their three dimensional (3D) autosomal dominant polycystic kidney disease (ADPKD) cell model. This painful genetic disorder is characterized by small fluid-filled cysts in the kidneys that lead to hypertension, hematuria, infection and kidney failure. Prior to using the Cytation 5, the cells were plated in 48-well format and imaged using a benchtop brightfield microscope. This process was extremely laborious and yielded limited data. The Cytation 5 offers high content imaging, and as its integrated Gen5™ Software evolved, it enabled the 3D ADPKD assay to be significantly enhanced and optimized. Now, the cells are seeded into 384-well microplates, and the Cytation 5 takes six individual brightfield images of each well at 4x magnification. It then automatically stitches the images together and performs a z-stack for a unique perspective, including qualitative and quantitative data, on each suspended ADPKD cyst and its clear central lumen. The live cell analysis system enables walk-away operation, so that researchers can attend to high-value activities while the cells are automatically cultured and imaged. Dr. Mai says, “We have other instruments in the lab that are just collecting dust, but we depend on all of our BioTek products so often that we instituted a formal scheduling system to keep track of who is using each instrument at a given time.”
Dr. Streiff added a new dimension to his research into taste bud cells by using Cytation 5 to create real-time movies. When growing taste bud cells to confluency in the bottom of 384-well microplates, he adds a dye that measures cytosolic calcium levels. As taste molecules are injected, individual taste bud cells activate and internal calcium levels spike. The movie-making feature shows how individual cells may react differently at particular taste molecule concentrations. Dr. Streiff maintains, “Data like graphs and concentration response curves from Cytation 5 are fantastic, but it’s the movies that make a huge impact. Our clients love to see the cells responding in real-time.”
“BioTek’s products, and especially the Cytation 5, give us a valuable throughput advantage from fifty to a hundred compounds depending on the assay,” asserts Matt Redmann, Ph.D., Head of Business Development at DiscoveryBioMed. “On top of that, the depth and breadth of data that we obtain using these instruments instills trust and value for our drug discovery clients.” Dr. Mai also extends credit to the people behind the products, adding, “The entire BioTek team, and especially our local BioTek contacts, really listen to us and take the time to understand our goal. We trust that they and their new and improved technologies will help us push our research forward.”
Video 1. Primary human taste bud epithelial cells in culture stained with calcium dye. Note the increase in calcium response from taste receptor activation from cells exposed to a tastant (left), compared to cells treated with vehicle (right).
To learn more about DiscoveryBioMed, Inc., visit their web site.
Thanks to Dr. Erik Schwiebert at DiscoveryBioMed, Inc. for sharing his BioTek experience.