Spatio-temporally precise activation of engineered receptor tyrosine kinases by light.

Receptor tyrosine kinases (RTKs) are a large family of cell surface receptors that sense growth factors and hormones and regulate a variety of cell behaviours in health and disease. Contactless activation of RTKs with spatial and temporal precision is currently not feasible. Here, we generated RTKs that are insensitive to endogenous ligands but can be selectively activated by low-intensity blue light. We screened light-oxygen-voltage (LOV)-sensing domains for their ability to activate RTKs by light-activated dimerization. Incorporation of LOV domains found in aureochrome photoreceptors of stramenopiles resulted in robust activation of the fibroblast growth factor receptor 1 (FGFR1), epidermal growth factor receptor (EGFR) and rearranged during transfection (RET). In human cancer and endothelial cells, light induced cellular signalling with spatial and temporal precision. Furthermore, light faithfully mimicked complex mitogenic and morphogenic cell behaviour induced by growth factors. RTKs under optical control (Opto-RTKs) provide a powerful optogenetic approach to actuate cellular signals and manipulate cell behaviour.

[Advances in synthetic physiology of artificial genetic parts].

Artificial genetic parts should be modularized and can be predictably scaled up via assembly or reused in other contexts. Under intracellular physiological conditions, however, the functions of the assembled parts are severely impeded by multi-level physiological interference, i.e., most artificial assembled systems cannot be functional as predicted. Here we proposed a concept of synthetic physiology, defining it as the branch of synthetic biology to investigate and control interferences between artificial genetic parts and intracellular physiological system. Under such framework, we describe the part-host interactions and review the methods and strategies used to characterize and address these interactions.

The optogenetic promise for oncology: Episode I.

As light-based control of fundamental signaling pathways is becoming a reality, the field of optogenetics is rapidly moving beyond neuroscience. We have recently developed receptor tyrosine kinases that are activated by light and control cell proliferation, epithelial-mesenchymal transition, and angiogenic sprouting-cell behaviors central to cancer progression.

Advances in synthetic physiology of artificial genetic parts / 生物工程学报

Artificial genetic parts should be modularized and can be predictably scaled up via assembly or reused in other contexts. Under intracellular physiological conditions, however, the functions of the assembled parts are severely impeded by multi-level physiological interference, i.e., most artificial assembled systems cannot be functional as predicted. Here we proposed a concept of synthetic physiology, defining it as the branch of synthetic biology to investigate and control interferences between artificial genetic parts and intracellular physiological system. Under such framework, we describe the part-host interactions and review the methods and strategies used to characterize and address these interactions.