ID: 2017-044 A bio-assay for rapid screening and detection of nuclear hormone receptor modulators (see also 2016-053)
Principal Investigator: Bradley Bundy
Existing transcriptionally activated biosensors employ living cells such as yeast (Saccharomyces cerevisiae) or immortal human cancer cell lines (MF7) as the platform for measuring nuclear hormone receptor activity. These assays require hours or days (18 hours at the very least) and extensive laboratory training to execute. Furthermore, cell walls and membranes may interfere with the diffusion of test molecules and reporter proteins to and from the cell. This work utilizes cell-free protein synthesis reactions in place of whole cells to synthesize nuclear hormone receptors, transcription co-factors, and reporter proteins to create a portable, optimized biosensor assay. The just-add-sample assay is executed in 20-30 minutes.
The Bundy lab previously created the RAPID cell-free protein synthesis biosensor that utilizes an allosteric fusion protein as a ligand-binding reporter. This assay achieves a limit of detection (LOD) in the nano-molar range. It is expected that the signal amplification associated with the transcriptional activation biosensor will enable LODs in the pico-molar range.
This technology is to be used for in-field detection and high-throughput screening of endocrine disruption chemicals (EDCs). It may also be used as a medical diagnostic and research tool.
About the Market:
The increased endocrine disease rates parallels increased production of manufactured chemicals. Global production of plastics grew from 50 million tons in the mid-1970s to nearly 300 million tons today. Similar trends hold for other chemical sources including pesticides, fire retardants, solvents, and surfactants. Sales for the global chemical industry have sharply increased from USD$171 billion in 1970 to over USD$4 trillion in 2013. Human exposure may cause some health effects, such as lower IQ and adult obesity. These effects may lead to lost productivity, disability, or premature death in some people. One source estimated that, within the European Union, this economic effect might have about twice the economic impact as the effects caused by mercury and lead contamination. The socio-economic burden of EDC-associated health effects for the European Union was estimated based on currently available literature and considering the uncertainties with respect to causality with EDCs and corresponding health-related costs to be in the range of €46 billion to €288 billion per year.
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