21:I[432972,["/_next/static/chunks/bb923814e1f4d2e9.js","/_next/static/chunks/dd3ee9f5b7716ca6.js","/_next/static/chunks/4204a0ae82542ca8.js","/_next/static/chunks/30036bedc5269936.js","/_next/static/chunks/6e1aa89a642f40be.js","/_next/static/chunks/cd5e572bc3e4eb92.js","/_next/static/chunks/8ffd0b71567920d8.js","/_next/static/chunks/67ea6dfd21f16c5f.js","/_next/static/chunks/24eb4379f68013fd.js","/_next/static/chunks/b8cd775ffdf935bd.js","/_next/static/chunks/983103cd9eb7b428.js","/_next/static/chunks/d4ac9dcf27f6ff52.js","/_next/static/chunks/294b9525248c8e5f.js"],"default"] 22:T41f,Since the removal of senescent cells in model organisms has been linked to rejuvenation and increased lifespan, senotherapies have emerged to target senescent cells for death. In particular, interleukin-6 (IL6) is a prominent senescence-associated secretory phenotype (SASP) and, thus, seeking IL6 could potentially localize engineered cells to senescent cells for therapeutic intervention. Here, we engineered a chimeric IL6 receptor (IL6Rchi) that generates a Ca²⁺ signal in response to IL6 stimulation. When IL6Rchi was co-expressed with an engineered Ca²⁺-activated RhoA (CaRQ), it enabled directed migration to IL6 in cells that have no such natural ability. Next, the removal of target cells was accomplished by the mechanism of membrane fusion and subsequent death. This work represents a first step towards engineering a cell to target senescent cells that secrete high levels of IL6. For increased specificity to senescent cells, it will likely be necessary for an engineered cell to recognize multiple SASPs simultaneously.23:T495,The versatility of Ca²⁺ signals allows it to regulate diverse cellular processes such as migration, apoptosis, motility and exocytosis. In some receptors (e.g., VEGFR2), Ca²⁺ signals are generated upon binding their ligand(s) (e.g., VEGF-A). Here, we employed a design strategy to engineer proteins that generate a Ca²⁺ signal upon binding various extracellular stimuli by creating fusions of protein domains that oligomerize to the transmembrane domain and the cytoplasmic tail of the VEGFR2. To test the strategy, we created chimeric proteins that generate Ca²⁺ signals upon stimulation with various extracellular stimuli (e.g., rapamycin, EDTA or extracellular free Ca²⁺). By coupling these chimeric proteins that generate Ca²⁺ signals with proteins that respond to Ca²⁺ signals, we rewired, for example, dynamic cellular blebbing to increases in extracellular free Ca²⁺. Thus, using this design strategy, it is possible to engineer proteins to generate a Ca²⁺ signal to rewire a wide range of extracellular stimuli to a wide range of Ca²⁺-activated processes.

#	Concept	H-Index	Publications	Citations
1	Medicine	1	1	23
2	Allergy	1	1	23
3	Biology	1	1	23
4	Immunology	1	1	23
5	Autoimmune Disease	1	1	23

	Year	Citations

About

Top Concepts