Technology: Biosensor development for application of robotic microscope technology

• Steve Finkbeiner, M.D., Ph.D.
  Senior Investigator and Associate Director, Gladstone Institute of Neurological Disease
  Professor of Neurology and Physiology, University of California, San Francisco
  Director, Taube/Koret Center for Neurodegenerative Disease Research
  Director, Hellman Family Foundation Program in Alzheimer's Disease Research
  

• Gaia Skibinski, Ph.D.
  Postdoctoral fellow
  

Overview

During the last 2 years we have identified novel orphan GPCR functions in neurons, demonstrating that phenotypes can be identified for understudied targets. This initial phenotypic data can be used to prioritize genes for further screening in additional functional assays or translational models (e.g., models of neurodegeneration). Expanding our phenotypic screen to a larger subset of orphan genes would provide a basis to validate in silico predictions based on bioinformatic interrogation (e.g., predictive models of gene expression patterns in neurons).  We have shown that we can use robotic microscope technology (RM) and the physical exam of the cell (PEC) to screen orphan genes for multiple phenotypes in neurons.  The technology is scalable, both by the number of genes and phenotypic assays that could be screened.  The technology can be adapted to more complex models (e.g. case study of imaging zebrafish). The value of integrating bioinformatic interrogation with experimental approaches and the necessity of an iterative loop between these disciplines. The identification of novel dark gene functions: a) requires very sensitive phenotypic tools; b) might require additional peturbations (aside for modulation of levels/function by genetic manipulation or small molecules).