Research|Nanoengineering ion channels
Nanoengineering ion channels for tailored function
Our goal is to achieve noninvasive control of cellular signaling through engineering ion channels or other signalling molecules with multidisciplinary approaches including chemical biology, protein engineering and nanotechnology. Specially, we will explore the use of light, magnet and radiowave to remotely control ion channel activities and their downstream effectors.
The neuroscience field has witnessed the successful use of channelrhodopsin (ChR)-derived optogenetic tools to perturb and observe the activity of excitable neurons at precise locations and times. Nevertheless, ChR lacks ion selectivity and often causes intracellular pH alteration. There is an urgent need to expand the repertoire of light-switchable or optogenetic tools with tailored ion selectivity that can be applied to study cellular signaling in non-excitable cells. Efforts will be directed to further screen calcium-selective ChR variants by taking site-directed mutagenesis and protein engineering approaches. More importantly, built upon our prior findings, we will attempt to engineer the highly calcium-selective ORAI1-STIM1 pathway for non-invasive manipulation of calcium signaling by light. Efforts will also be directed to engineer T cells with novel functionality to kill tumor cells.
The light-switchable tools, along with specific small molecule inhibitors for ORAI1 channels, will allow me to interrogate calcium signaling in both excitable (e.g., neurons) and non-excitable cells (e.g., T lymphocytes and embryonic stem cells ) and mouse models at precise locations and times. The ultimate goal is to extend similar approaches to install light-sensitive moieties to other molecules for remote controlling of cellular signaling.