University of Massachusetts (UMass) chemistry professor Bob Weis, with former doctoral students Anthony Shrout and David Montefusco, have received a US patent for their invention, template-directed assembly (TDA) of receptor-signaling complexes, a new method for studying signaling processes found in all cells.
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Mr Weis said that abnormal signaling contributes to many diseases such as cancer and diabetes, so the method can be used to develop new drugs for the diseases.
The new method reassembles ‘teams’ of signaling proteins normally found on the cytoplasmic side of the cell membrane by simply mixing together individual components with a synthetic scaffold membrane to facilitate the reassembly process.
Additionally, the reassembled team has many of the functions it would have in the cell, which allows drug developers and researchers to conduct rapid, accurate assessments of molecules that target a specific pathway. For example, it is possible to study the teams of proteins found in tyrosine kinase pathways, a type frequently involved in cancer. Using the new tool in such studies, researchers can test for new drugs to target these pathways.
Mr Weis added that scientists now understand the cell’s interior to be more like a thick porridge packed with proteins, nucleic acids, interior membranes and other components, and less like a thin soup. Proteins carry out thousands of cell operations, many of which involve the transfer or transduction of information signals via these protein interactions. This work is carried out in part by the proteins achieving a ‘lock and key specificity,’ but also by organising the necessary components near one another in the cell and in appropriate orientation.
Reportedly, researchers have long tried to mimic these delicate phenomena in the laboratory, but without a way to hold several dynamic puzzle parts together in the correct alignment, the key proteins drift away from each other and fail to interact in the way they normally would in a cell. The new invention provides a way to bring the signaling proteins together and in the arrangement needed to function.
The invention is ‘generally applicable to many cellular signal transduction systems of interest to the pharmaceutical industry.’ As a result, Mr Weis and colleagues formed Protein Attachment Technologies or PA Tech, in 2006, which licensed the technology from UMass Amherst to develop and sell the new reagents and assay methods that result from the combination of engineered proteins and chemical self-assembly.
The researchers said: “The company’s products and reagents are designed to be particularly well-suited for biochemical tests of function in complex-signal transduction pathways involving membrane-associated receptors and proteins, a difficult but important set of targets in the pharmaceutical industry.”
Mr Weis said: “Because of the broad applicability to many different membrane-associated proteins, PA Tech sought out and formed an alliance with a sublicensee, Blue Sky Biotech of Worcester, a firm into the area of protein engineering and expression technologies.”
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