Combinatory Modulating T Cell Activation and Differentiation with Synthetic Signaling Molecular Swit

来源 :2015合成生物学青年学者论坛 | 被引量 : 0次 | 上传用户:zhengwei2
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  Sensing the environmental signals and making proper decisions are crucial for mammalian cells.A number of highly conserved signaling transduction kinase modules evolve to deal with environmental signals with complicated response dynamics.The spatial, temporal and quantitative changes of signaling dynamics determine cell-fate, such as proliferation, differentiation, and apoptosis.It is feasible to change cell fate by quantitative and predictive modifying few momentous signaling pathways.Adoptive T cell therapies have play a role in cancer treatment and regenerative medicine.But the safety and accurate fate control of transferred T ceils became peoples focus.It has been reported that the complex dynamic activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-B)signaling pathway could determine the activation and differentiation of T cells.So our interest is to re-engineer T cells signaling pathways to perturb their activation and differentiation processes.We chose many effector proteins derived from bacterial pathogens, which could influence the activation of MAPK or NF-B signaling pathway.Moreover, we develop specific molecular switches, using drugs or light inducible systems, to control the quantity and time course expression of these proteins.After quantitatively modulating the time and strength of the activation of both MAPK and NF-B pathway, we hope to achieve a temporal and spatial control of immune T cells activation and differentiation in vitro and in vivo.
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