Difference between revisions of "Part:BBa K3132016"

Revision as of 12:17, 17 October 2019

Generalized extracellular molecule sensor platform

Why we choose GEMS: GEMS, which is also named as Generalized Extracellular Molecule Sensor, is a highly generalizable modular platform that was first published in 2018. In this literature, the author constructed sensors for non-signaling molecules with a wide range of molecular weights to confirm the validity and generalizability of the GEMS, and found these GEMS devices are the first examples of 2.sensing soluble molecules with scFv-coupled receptors that 1.utilize natural signaling cascades rewired for transgene expression,unlike the previous membrane surface receptors which can only detect membrane marker. 3.The easy adaptability of the GEMS platform to new targets should make it a useful tool for many applications in synthetic biology and for developing novel precision-guided cell-based therapeutics. Structure of GEMS: GEMS consists of three structural domains: an extracellular domain, a transmembrane domain, and an intracellular domain (fig.1).The extracellular domain is based on an EpoR scaffold. After introducing a mutation into the erythropoietin receptor to render it inert to erythropoietin, it can be fused to affinity domains such as antibody fragments, then the two form a whole as extracellular receptor for signals. The EpoR transmembrane domain was fused to the intracellular signal transduction domains. Once activated, these intracellular domains can induce downstream signaling pathways and regulate gene expression. Mechanism of GEMS: Inactive EpoR dimers are locked by transmembrane helix interactions in a conformation that prevents downstream signaling. Ligand binding to the receptors is thought to rotate each receptor subunit around its own axis and is likely accompanied by an increase in the distance between intracellular domains. The combination of these effects triggers downstream signaling (fig.2).

Sequence and Features