Study of Phagosome Maturation Rate in AMD according to the Circadian Rhythm
MentorDavid Williams, PhD
The goal of this project is to identify what POS phagosome stages and at what time of the day are more impacted during phagosomal degradation in AMD. In Aim 1, I will test which stages of POS phagosome degradation are most impacted in cultures of human RPE cells carrying the AMD risk alleles. These studies will allow me to test in detail for defects in phagosome maturation and resolve which part of the degradation pathway impacts phagosome maturation. In Aim 2, I will assess which stages of POS phagosome maturation are most impacted, according to the daily cycle, in two in vivo mouse models (Klc1-/- and Elovl4-TG2 mice), in which there is an overall delay in POS phagosome degradation and which possess macular degeneration-like pathology.
Phagosome degradation is impaired in AMD, which leads to the accumulation of RPE deposits. However, the precise mechanism by which this happens is still unknown. Previously, I have developed a way to identify different phagosome stages during the maturation process. Also, I have found that the maturation rate between these stages varies throughout the daily cycle. Therefore, in this project, I will combine both findings to analyze what phagosome maturation stages are more impacted in AMD cells and according to the daily cycle. Once the study is complete, we will have more precise information about this mechanism that is impaired in AMD. We will also know if it is more affected at specific times of the day. This could help us to develop ways to ameliorate the impacted process.