Research

Focus

In general terms, the Fischer lab studies neural development, regeneration and survival. In particular, the Fischer lab focuses on the development, regeneration and survival of cells in the neurosensory tissue of the eye, the retina. The lab studies retinal regeneration from neural stem cells derived by reprogramming of the support cells of the retina, the Müller glia.

The use of stem cells for neuron replacement and trophic support holds the potential to treat degenerative diseases of the central nervous system. Dr. Fischer’s work has identified neural stem cells at the peripheral edge of the retina.  These cells are capable of proliferating and generating neurons at increased rates with the application of growth factors. In addition, he has demonstrated that mature Müller glia in the retina can become neuron-producing retinal precursor cells in response to acute damage or growth factors.

Approaches

Current projects include the use of: scanning laser confocal microscopy; epifluorescence microscopy; digital image processing and analysis; in situ hybridization; quantitative polymerase chain reaction (PCR); virus-mediated gene transfer; gene silencing or over-expression using AAV’s; immunocytochemistry for peptides, neurotransmitters, receptors and structural proteins; and single cell RNA-seq, single cell ATAC-seq, RNA velocity on scRNA-seq data and the bioinformatics associated with large aggregate libraries of 50,000+ individual cells.

Core Resources

The Fischer Lab manages a 10X Genomics platform for the Department of Neuroscience. This includes the 10X Chromium Cell Controller, 10X Chromium X HT Controller, Miltenyi GentleMACS Octo dissociator, Miltenyi MACS Cell Separation and Countess Automated Cell Counter. We regularly consult and generate libraries for scRNA-seq, scATAC-seq and multi-omic libraries.  In addition, we perform bioinformatic analyses including generating gene-cell matricies (10X Cell Ranger) and different analyses using Seurat, Monocle, Signac, SoupOrCell, GO enrichment analyses and SingleCellSignalR.

The Fischer Lab also manages a Leica SP8 point scanning laser confocal that is equiped with 4 excitation lasers, hybrid GAsP detectors and spectral scanning. The system is set-up on an upright microscope.

Video Description: 3D visualization by tSNE from a chicken muller glia sc-RNA seq dataset