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The goals of the St-Pierre lab are to design, characterize, and deploy protein tools to accelerate neuroscience research and broader applications. We focus on the development of genetically encoded fluorescent markers/sensors and optogenetic actuators. 


The complexity of the brain makes it challenging to study. For example, mouse brains contain 108 neurons and as many (or more) glia.  Neurons on average have ~8,000 synapses from other cells. Through changes in membrane voltage, neurons process and communicate these inputs to other cells on a millisecond timescale. Disruption of this tightly controlled process is thought to be involved in many neurological disorders. Thus, one of the long-standing goals in neuroscience is to perform all-optical electrophysiology or multi-color imaging. Either of these methods would enable large-scale monitoring/manipulation of neural activity non-invasively with cell type-specificity. To further accelerate the development of optical sensors and actuators, the need arises for high-throughput protein engineering and screening methods. Regulated expression of these new tools will also be critical to prevent toxic overexpression in some cells and subdetection levels in others.  


Our current projects focus on three broad themes:

  1. Genetically encoded voltage indicators for imaging rapid neural activity (Alex and Michelle) 

    • Genetically encoded voltage indicators are emerging tools for monitoring voltage dynamics with cell-type specificity. However, the current generation of indicators enable a narrow range of applications due to poor performance under two-photon microscopy (a method of choice for deep-tissue recording). To improve indicators, we developed a multiparameter high-throughput platform to optimize voltage indicators for two-photon microscopy. Using this system, we develop genetically encoded voltage indicators including the recently published JEDI2P which is faster, brighter, more sensitive and photostable than its predecessors. 

  1. Automating the High-Throughput Screening of Protein-Based Optical Indicators and Actuators (James) 

    • Engineering biosensors and actuators are often expensive, time-consuming and labor-intensive. We combine high-throughput and high-content approaches to accelerate the optimization of complex properties of proteins.  

  1. Synthetic circuits for buffering gene dosage variation (James) 

    • Precise control of gene expression is critical for biological research and biotechnology. However, transient plasmid transfections in mammalian cells produce a wide distribution of copy numbers per cell, and consequently, high expression heterogeneity. We develop genetic circuits to reduce gene expression variability in mammalian cells.  


We adopt multidisciplinary approaches, combining techniques from synthetic biology, electrical engineering, optics, and computational biology, and neuroscience. We focus on integrated solutions that combine wetware (e.g. new biosensors or cell lines), hardware (e.g. custom microscopes) and software (e.g. new signal/image analysis software). Our multidisciplinary approaches are reflected in the diverse backgrounds of our team members.

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