Method development to investigate the assembly of a ternary holoreceptor complex**

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The grant proposal consists in establishing a method to quantify binding affinities between a signaling protein and a combination of receptors and coreceptors in vitro. Paraza Pharma is a fully integrated research organization developing biotechnological application. The company aims to develop novel methods for the purification of secreted and membrane integral proteins that contribute to signaling and cellular communication at the cell surface; another aspect of the project aims at elucidating the formation of an holoreceptor transducing signal from the extracellular milieu to the cytoplasm upon binding of a signaling protein with its putative receptor/coreceptor complex. Understanding how a signaling protein binds to a holoreceptor complex composed of a combination of receptors and coreceptors remains a fundamental question and a technical challenge raised by Paraza Pharma. Such project requires highly sensitive biophysical methods to measure binding affinities between the diverse protein components of the signaling pathway, as well as it requires specialized expertise in the field of membrane proteins, which are considered challenging samples due to their intrinsic instability and difficulty to manipulate in vitro. Dr. Calmettes, an expert in membrane protein characterization and macromolecular crystallography, will develop for Paraza Pharma a method to produce and purify membrane-signal-transducing proteins and to quantify their binding affinities with a cognate signaling protein. The experimental design to be developed is highly relevant for the Canadian industry and the advancement of knowledge in Canada; it is anticipated to open new avenues for the development of future applications in biotechnology, bioscience and bio-industrial sectors in Canada.