The New SyncroPatch 384i

December 19, 2022

Drs. John Spudich and Elena Govorunova

The Center for Membrane Biology has acquired the SyncroPatch 384i, a state-of-the-art, high-throughput, fully automated patch-clamp system with a multi-PI equipment grant from NIH. The instrument with robotic components independently and simultaneously monitors ion currents in up to 384 cells expressing voltage-gated, ligand-gated, or light-gated channels, or ion exchangers or ion pumps. The system has a state-of-the art pipetting system for programmed delivery of ligands or other chemicals, and sophisticated components that also deliver voltage changes or light pulses as stimuli.

The SyncroPatch greatly accelerates research on mechanisms of ion-conductive channels and active transporters because it allows simultaneous measurements in 384 cells in individual micro-wells in parallel, eliminating the need for manual patch-clamping of individual cells, a slow laborious process applied to cells one-by-one. The instrument also accelerates screening of drugs for many human diseases involving ion channel disfunction, such as epilepsy, Parkinson’s disease, tachycardia, long QT syndrome and other cardiac arrhythmias.

Seven laboratories in McGovern Medical School in the Departments of Biochemistry & Molecular Biology, Integrative Biology, and Neurobiology & Anatomy have planned experiments on the SyncroPatch 384i to monitor or screen stimulus-induced ion currents in various excitable cells, such as neurons or cardiomyocytes, as well as microbial channels such as channelrhodopsins used in optogenetics for photocontrol of excitable cell firing. Research Associate Professor Elena Govorunova in the Spudich lab is the technical manager of the SyncroPatch 384i system. The instrument will be available also to users in other institutions, and already several laboratories from UTMB, Baylor and Rice University have participated with preliminary data in the multi-user grant proposal that enabled NIH-funded purchase of the SyncroPatch.

The SyncroPatch 384i, will enable us to interrogate ion channel function at an unprecedented pace, accelerate discoveries of new optogenetic tools and new therapeutics, and thus broaden the horizon of biomedical research and drug development. The research group of Dr. Spudich will be the major user of the system, and the groups of Drs. Jayaraman and Serysheva will be its minor users. The instrument will operate within the Center for Membrane Biology and will also be accessible for researchers from other GCC institutions.

Two major classes of channelrhodopsins that differ in their ionic selectivity are cation channelrhodopsins (CCRs) and anion channelrhodopsins (ACRs), used for excitatory and inhibitory optogenetics, respectively. Inhibitory optogenetic tools are particularly important because reversible and temporally precise suppression of neuronal activity is key to revealing the causal roles of specific neurons in network dynamics and behavior. However, compared to excitatory tools, inhibitory tools remain underdeveloped because potent inhibitory proteins have only been recently discovered, exhibit limited spectral diversity, and have undesired activating effects in some conditions. Thus, our major goal is to discover and engineer a toolkit of robust optogenetic inhibitors. The SyncroPatch will greatly accelerate this research, because it allows simultaneous measurements in 384 cells in parallel. We have been granted access to this instrument during a Nanion pilot program. The SyncroPatch enabled us to complete characterization of three novel ACRs and two CCRs, and collect statistically significant data in just a few days, as compared to several weeks or even months required to accomplish the same task using manual patch clamp.

The SyncroPatch acquisition will facilitate further development of optogenetic tools for basic and translational research, and channelrhodopsin-based gene therapy. The anticipated results are better understanding of pathological mechanisms of many human diseases involving ion channel disfunction, such as Parkinson’s disease, epilepsy, cardiac arrhythmias, and blindness, and the development of new therapies to prevent and cure them.

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