Small Molecule Discovery
The whole concept of flow cytometry is quite simple, observed Larry Sklar, Ph.D, principle investigator at the University of New Mexico Center for Molecular Discovery, who explained that “when people run flow cytometers, one sample is one file.
“Generally, flow cytometry doesn’t do high throughput—doesn’t do many samples very well, very quickly—so we created a platform to solve that problem. Our technology is high-throughput flow cytometry, which is intrinsically high content because you can make many measurements simultaneously.”
Eric Prossnitz, Ph.D., professor of cell biology and physiology at the University of New Mexico, spoke extensively about the HyperCyt flow cytometry platform for high-content high-throughput small molecule discovery. “The platform is evolving for 1,536-well plates and direct sample delivery. Recently, we demonstrated HTS applications with primary cells and yeast multiplex model systems for TOR pathway analysis, as well as innovative molecular assays for intracellular trafficking pathways.”
The platform can be used to make molecular measurements using assemblies of protein-protein or protein-small molecule interactions on particles. “This is a unique technology that is still in development. One of the challenges we have is keeping up with the sheer throughput of the technologies that are already well established. We can work with complex cell suspensions, bacteria, and yeast in suspension. We can look at, not just high content, but also multiple processes and multiple targets simultaneously, because of the way flow cytometry can color code samples and analyses.”
Dr. Prossnitz seeks molecules that can regulate physiological processes. “Fundamentally, we are interested in understanding complex interactions between estrogen and its multiple receptors. Until a few years ago, there were two known receptors and it was thought that all interactions were mediated by those two receptors. It’s been somewhat challenging to make headway in this space.”
“Fortunately, we isolated a compound that selectively activates the new receptor GPR30, which was published in 2006. Since then, over 30 or so publications have used this probe to ask questions in almost all areas of physiology and biology; without this probe, it would have been far more difficult to ask these questions.”
Dr. Sklar noted that the flow cytometry platform is well suited to fill a unique niche in small molecule identification for cell and molecular assays in suspension, especially in complex cell suspensions for primary cells, hematopoietic stem cells, and leukemia.