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Cell-based assay platforms-more physiologically relevant and automated than ever-enhance not just drug discovery but translational medicine, too.

Lisa Heiden

Cell-based assay platforms are evolving to meet diverse challenges-mimicking disease states, preserving signaling pathways,  modeling drug responses, and recreating environments conducive to tissue development.

As diverse as these applications may be, the innovations that make them possible may be aligned with just a handful of themes.

These themes, which are expressed in varying degrees in most of the newer cell-based assay platforms, include the following:

• Use of primary rather then established cell lines.
• Development of tools for making physiologically relevant environments.
• Incorporation of Big Data strategies.
• Integration of high-throughput screening (HTS) and automation methods.
• Leveraging of signaling pathway mechanisms.

Be alert to these themes as we consider five different cell-based assay platforms. Three of these platforms are scheduled to be presented at an upcoming event organized by the Society for Laboratory Automation and Screening (SLAS). This event, the SLAS Conference and Exhibition, will take place February 7?11 in Washington, DC. The other two platforms were discussed at an event organized by the SMi Group. This event, Advances in Cell Based Assays, took place late last year, in London.

These platforms demonstrate how today’s cell-based assays are driving translational medicine. These assays are creating opportunities that yesteryear’s scientists could only dream about.

Profiling Signaling Pathways

Maite Romier, a research and development project leader at Cisbio Bioassays, intends to present at the SLAS event. Her presentation, entitled, “New cell-based HTRF assays deserve the exploration of Wnt signaling pathway,” describes how emerging concepts in Wnt/beta-catenin signaling can be translated into practical assays.

“We chose to develop the new HTRF (homogenous time-resolved fluorescence) assay as part of our innovation efforts to provide cell-based solutions for phosphoproteins, and for cell signaling pathway investigation in general,” explains Romier.

The HTRF platform is a complete, well-established assay system that already covers 10 major pathways. Based on an “add and read” homogenous protocol-a robust alternative to ELISA or bead-based technologies-HTRF “simply enables a fast analysis of what’s happening in the cell.”

“Specifically, the cell-based phospho/total beta-catenin assay was undertaken to allow the investigation of the Wnt signaling pathway, an area of growing interest for drug discovery researchers,” continues Romier. “Wnt signaling controls the phosphorylation status of beta-catenin, a critical regulator and key protein in the pathway. This assay serves as a pathway readout when trying to modulate the pathway in the disease state.

“Total beta-catenin is an important co-tranional activator of many significant genes involved in differentiation, development, cell proliferation, and hence cancer. Our results showed that the assay can distinguish between pools of cellular endogenous beta-catenin whether phosphorylated or not, which have different important functions in cell signaling. Screening for compounds using the beta-catenin assay seems very promising for discovering new drug mechanisms in the cancer field.”

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