Cell Biology, Neurobiology & Anatomy

Research Area: Photoreceptor Biology

I began working in the Besharse lab as part of the technical staff after graduating from college in 2000. After having the chance to get involved in a wide variety of projects in the lab under the direction of others, I realized that I wanted to be able to be more independent and learn how to identify good scientific questions myself, and so in 2007 I entered the graduate school through the Interdisciplinary Neurosciences Program. My work there has been a continuation of a project that I started in the lab before I made the return to school.

My project involves the study of a mouse line in which a mutation causing retinal disease spontaneously arose. These mice develop a condition known as fundus albipunctatus within the first two months, accompanied by profound functional loss of vision that can be measured by electroretinography. Later on, the condition progresses into a slow retinal degeneration. The mutated gene was identified in a SNP mapping panel as MFRP (membrane-type frizzled related protein). This is the second documented mutation in mouse MFRP, and the only complete knockout. This gene is interesting to me for two reasons. First, while MFRP is expressed exclusively in the retinal pigmented epithelium (RPE), a thin layer of cells immediately behind the retina, the only identified effect of its disruption in mice is in the neural retina itself. It is well established that these two tissues are extremely dependent on each other. Specifically, the RPE is responsible for taking up and recycling the vitamin A pigment from the retina after it absorbs a photon of light. The non-cell-autonomous nature of the MFRP mutant phenotype fits well with that. Second, humans with mutations in MFRP have a developmental defect resulting in smaller eyes that accompanies the fundus albipunctatus, and therefore they are extremely farsighted. However, they lack the striking retinal degeneration that we see in mouse models. Mice, on the other hand, appear to have completely normal eyeball morphology. I find it extremely intriguing that there is the possibility of functional divergence in MFRP between mice and humans. My current line of research is to determine the function of this gene in the mouse model, which may lead to clues about what it may be doing differently in humans.