A proximity based general method for identification of ligand and receptor interactions in living cells

Generation of highly diverse peptide library by linear-double-stranded DNA based AND gate genetic circuit in mammalian cells

“…Ideally, the combination of high content peptide library with functional signal screen systems in intact mammalian cells would allow efficient panning of peptide library under physiological condition. Recently, Lerner and colleagues have developed a powerful autocrine-based signaling system which tethered peptide library to cell membrane and employed artificial signal transduction systems to observe peptide-transmembrane protein interaction (17)(18)(19)(20)(21)(22). Here, we provide a novel methodology for building high content peptide library in mammalian cells.…”

“…Recently, Lerner and colleagues have developed an autocrine-based signaling system in mammalian cell (17)(18)(19)(20)(21)(22). Through membrane-tethered peptide library and artificial signal transduction system, this new strategy could screen the agonist/antagonist peptides of GPCRs or ion channels.…”

Agonist Antibody Converts Stem Cells into Migrating Brown Adipocyte-Like Cells in Heart

“…Recently, we discovered such a dual-function enzyme while studying intracellular combinatorial antibody libraries that regulate cell fates, particularly when autocrine selections are used [1][2][3][4][5][6]. We have previously applied this system to isolate antibodies capable of differentiating stem cells into specific immune cell types, of inserting functional proteins within proteins, and of serving as a fluorescent cell reporter to identify ligand and receptor interactions [1][2][3][4][5][6]. Here, we wanted to select antibodies that regulate migration of hematopoietic stem cells to peripheral tissues.…”

Migration-based selections of antibodies that convert bone marrow into trafficking microglia-like cells that reduce brain amyloid β

“…The method is based on the selection of intracellular antibodies from combinatorial libraries that modulate cell fates. One can test the effects of up to 10 8 different antibodies and, because the selection system is autocrine-based where the target and the antibody are in the same cell, each cell is a reporter system unto itself ( 1 – 9 ). We have previously used this method to select for antibodies that differentiate or transdifferentiate stem cells and even turn cancer cells into those with alternative phenotypes ( 10 ).…”