Chemical Sensory Signal Transduction Pathways In Respiratory System And Its Applications In Biosensor Designing,Immune Monitoring And Drug Screening

In humans and other mammals,respiratory system is not only the vital system for gas exchange but also the frontline of defending against airborne hazardous substances.It's critical that the potentially harmful molecules are readily detected before the body can mount a robust response.While the olfactory sensation begins in the respiratory system,gustatory signaling molecules are also found there.Various cell types along the respiratory tract are equipped with olfactory or taste receptors and the downstream signal transduction pathways,acting as the sentinels in the airway epithelium.A better understanding of the chemical senses of the respiratory system could provide novel perspectives on how stress responses are orchestrated within the airway,and grant us inspirations in designing biomimetic sensors.The main focuses and innovations of this research are listed as following:1.The design of a novel in vivo biological electronic nose based on transgenic mice and brain-machine interface technology.The fluorescent M72 glomeruli on the olfactory bulb of M72-GFP mice offer guidance for precise electrode implantation,resulting in significant improvement of specificity and repeatability of odor detection.Experiments showed that the M72 in vivo electronic nose respond to benzene ring containing molecules in a highly specific way,which makes it a potentially applicable tool for explosive detection.2.Bitter tastants activate chemosensory tuft cells in tracheal epithelium and induce tuft cell hyperplasia.In our experiments using both in vivo stimuli inhalation and in vitro organoid models,we found that denatonium and N-Phenylthiourea could activate tuft cells in a bitter taste signal transduction pathway-dependent manner.The subsequent tuft hyperplasia is observed in both mouse tracheal epithelium and cultured airway organoids,suggesting an IL13-STAT6 independent pathway for tuft cell proliferation.3.Cancer organoids recapitulate structural characteristics and intratumor heterogeneity of human squamous cell lung cancer.Using the resected tumor tissue from a LUSC patient,we built an in vitro cancer organoids culture system.Histological and immunofluorescent characterizations of the cancer organoid showed considerable resemblance to the original tumor.In cisplatin treatment assays,the cancer organoids showed stronger resistance than the patient-derived 2D cell line,suggesting cancer organoids can be an innovative tool in drug screening.4.A tuft cell-like variant of human small cell lung cancer cell line possesses chemosensory ability and produces PGE2 in response to bitter stimuli.We discovered that NCI-H211 cells express multiple bitter taste receptors and the complete downstream signal transduction pathway.Just like the tuft cells in the airway,H211 can respond to bitter stimuli with an intracellular calcium wave.Denatonium treatment also increased COX2 expression level and PGE2 productivity in H211 cells.