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Emran, F.

Publications and source records attributed to Emran, F..

2 recordsLinked to original sources

Identifying molecular instructions to hard-wire a sensory neurons synaptic connectivity

The neural circuitry underlying innate behaviours must be pre-specified using precise molecular instructions. However, it is not clear what specific molecules are required to generate one neurons wiring pattern that make it distinct from a neighboring neurons wiring pattern. Here, we repeatedly sequenced three identified Drosophila sensory neurons that each have a unique and stereotyped hard-wired synaptic connectivity, to determine the cell surface molecules that distinguish their identities. Repeated sequencing of the same neuron between different animals revealed that the variability of transcription is < 1%. We find that less than 100 cell surface molecules can distinguish between a mechanosensory neuron from a chemosensory neuron. Functional characterization of the cell surface receptors verified their different roles in axonal and synaptic targeting. Finally, we expressed combinations of the different cell surface receptors to mis-wire the chemosensory neuron and increase its axonal branching.

neuroscience↗

A Drug Screening Platform for Protein Expression Levels in Neurological Disorders

Neurological and psychiatric diseases and disorders affect more than half of the population. Many of these diseases are caused by the malfunctioning of protein synthesis, where too little or too much production of a protein harms a cell and its functions within the brain. We developed a drug screening platform to identify compounds that target the primary cause of these diseases, namely protein expression amounts. This cellular assay monitors protein expression of a target disease gene along with the protein expression of a control gene using the Protein Quantitation Ratioing (PQR) technique. PQR tracks protein concentration using fluorescence. We used human cells and CRISPR-Cas9 genome editing to insert the Protein Quantitation Reporter into target genes. These cells are used in high-throughput drug screening measuring the fluorescence as the assay. Drug hits can be validated using the same PQR technique or animal models of the disease. HighlightsO_LIThe assay can identify drugs that directly address the molecular cause of a disease. C_LIO_LIThe Protein Quantitation Ratioing (PQR) technique allows for tracking and measuring protein amounts over time in single living cells before, during, and after drug administration. C_LIO_LIGenome editing to insert the PQR into the target gene allows tracking of endogenous protein expression. C_LIO_LIUsing human cell lines allow for faster production of knock-in cells. C_LIO_LIPatient mutations can be replicated using genome editing during the knock-in step. C_LIO_LIUsing induced pluripotent stem cells allow for an unlimited supply of genome edited differentiated cells such as neurons with the PQR knock-in reporter. C_LI

neuroscience↗