Humans have several hundred Micro RNA (miRNAs), which are small, non-coding RNA molecules, each regulating 200-300 genes. Recent research has suggested that certain miRNAs may both be an exciting biomarker for disease and also a realistic therapeutic target. In order to better understand miRNA biomarkers and to develop miRNA-based therapies for neurodegeneration, it is important to understand which cells in the body use which of these miRNAs. To accomplish this, we created a system which labels the miRNAs in one cell type to permit their purification away from the miRNAs of other cells. We are now generating mouse models with this system which will allow us to study microRNAs in two important cell types for neurological disease – motor neurons and microglia. The Dougherty Lab has extensive experience creating these types of mouse models and the Miller Lab has extensive experience working with miRNAs. We will first apply this technology to a disease of motor neurons, Lou Gehrig’s disease, but anticipate that this system will be useful for other researchers studying other neurodegenerative diseases.
Hoye ML, Koval ED, Wegener AJ, Hyman TS, Yang C, O’Brien DR, Miller RL, Cole T, Schoch KM, Shen T, Kunikata T, Richard JP, Gutmann DH, Maragakis NJ, Kordasiewicz HB, Dougherty JD, Miller TM. MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models. J Neurosci.;37(22):5574-5586, (2017).
Reddy AS, O’Brien D, Pisat N, Weichselbaum CT, Sakers K, Lisci M, Dalal JS, Dougherty JD. A Comprehensive Analysis of Cell Type-Specific Nuclear RNA From Neurons and Glia of the Brain. Biol Psychiatry.;81(3):252-264, (2017).
Updated January 2019