Available Rotation Projects
We are interested in understanding how disease affects the interplay between gene expression, protein function and neuronal activity. For example, in retinal degeneration the death of the photoreceptors in the outer retina results in the appearance of a type of maladaptive plasticity in the surviving inner retinal neurons, especially in the retinal ganglion cells, the neurons that funnel all retinal information into the brain. This corrupted form of plasticity degrades residual vision and prevents meaningful vision restoration. Similarly, in the autism-causing disorder known as Fragile X Syndrome, the absence of the gene FMR1 and its encoded protein FMRP, result in uncontrollable idiopathic spontaneous hyperactivity that corrupts brain circuits, from the hippocampus to the prefrontal cortex. FMRP is an RNA binding protein regulating translation of hundreds of proteins, and its developmentally regulated silencing affects neurogenesis and synaptogenesis in the embryo as well as synaptic plasticity in the adult. Overall, our efforts are to understand how the two-way feedback regulation between neuronal activity and gene expression breaks down in disease, and whether it can be rescued.
To study all these, we use a combination of molecular biology (gene expression, gene manipulation, protein labeling, fluorescent reporters); electrophysiology and imaging (multi-electrode arrays, single-cell patch-clamp, calcium imaging, neuronal morphology reconstruction), and behavioral assays (operant-conditioning, fear-conditioning, innate behavior). We work in-vitro with immortalized cell lines (HEK cells) and human embryonic/ induced pluripotent stem cells (hESCs, hiPSCs); in-vivo with mice and rats; and ex-vivo (when available) with human or primate biopsies.
Rotation projects available at the Telias Lab:
Pharmacological and genetic manipulation of retinoic acid receptor expression and activity in cell cultures and in mouse retina. The project involves working with cell cultures and mice, using several methods including imaging of fluorescent dies and reporters, RNA and protein extraction, RNA-seq, WB and co-IP.
Manipulation of P2X7 phosphorylation in dissociated retinal cells and in cell cultures, and correlation to downstream transcription factor activation. Methods are similar to #1.
FACS-sorting of in-vitro and in-vivo cell samples labeled with custom-built fluorescent reporters, followed by RNA-seq and bioinformatics analysis. This project involves developing the skills necessary for intraocular injections in living animals.
Genetic engineering of an anti-RAR and anti-P2X7 silencing therapy in mice.
Building and testing a new behavioral paradigm for innate light avoidance assay in mice.
* Projects 1-4 all involve fluorescent imaging and extracellular recordings performed using a state-of-the-art two-photon microscope and multielectrode array (MEA).