G-protein coupled receptors (GPCR) are important family of membrane proteins involved in a variety of biological processes in the body. Due to their crucial role approximately near 30% of drugs are currently targeted to GPCRs. Complex mechanism of action and dynamic nature of GPCRs make them challenging targets in structural biology. Moreover, stability of GPCRs outside of native lipid membrane is decreased. Therefore, systemic pipeline for purification and reconstitution in lipid environment is crucial to facilitate structural and conformational studies of GPCRs. We aim to investigate the effect of membrane mimetic systems on obtained resolution as well as potential stabilization of different conformations and dynamics of GPCRs compared to detergents. This project is focused on utilizing saposin-lipid nanoparticles for optimization of purification and reconstitution of exemplar class B GPCRs such as Secretin receptor. Secretin receptor is expressed in Hi5 insect cells and solubilized using detergents such as DDM/CHS. The receptor was purified using affinity chromatography followed by size exclusion chromatography. Purified receptor in DDM/CHS was then incorporated in saposin-lipid nanoparticles by addition of saposin and lipids. Incorporated receptors were then screened using cryo-EM. Secretin receptor in apo form was successfully purified in DDM/CHS. Different incorporation conditions were screened to achieve highest efficiency. Purified SecR in sapodisc was applied to freshly glow discharge Au grids and data was collected on Talos Glacios. Data processing is in progress. Overall, this project explore new technologies that can support membrane protein biochemistry and structural analysis by Cryo-EM to obtain high-resolution structural data that is required to facilitate structure-based drug design.