<b>Impact of CKI alpha expression on models of retinal degeneration in fruit flies</b>

<p dir="ltr">Apoptosis is a natural process essential to development and homeostasis in multicellular organisms. Dysregulation within this process can lead to a wide variety of diseases, including neurological diseases and cancer. Outside of the causative genes of disease, extensive phenotypic heterogeneity exists within apoptotic diseases due to natural genetic variation that influences the apoptotic response. This genetic variation has a great potential to illuminate the complex mechanisms governing this heterogeneity as well as present novel avenues for therapeutics which can bypass the causative genes of disease. In this study, we investigate four candidate modifier genes of apoptosis indicated in past computational studies through the use of <i>Drosophila melanogaster</i> models of apoptosis to evaluate their impact on the apoptotic response Utilizing eye size as a readout of cell death and degeneration, we determined that three of the four genes acted as functional genetic modifiers of apoptosis: <i>CG31523</i>, <i>SPoCK</i>, and <i>CKI</i><i>α</i>. We further investigated <i>CKI</i><i>α</i> due to its strong modification of multiple apoptotic pathways. We investigated if <i>CKIα</i> modified the apoptotic response through its regulation of β-catenin. The silencing of <i>CKI</i><i>α</i> lead to possibly biologically relevant changes in expression of downstream β-catenin transcriptional targets related to apoptosis: <i>CycD</i>, <i>AXN</i>, and <i>MYC</i>. However, further investigation into the mechanism in which <i>CKI</i><i>α</i> functions as a modifier of apoptosis is required. Increasing the understanding of the mechanisms behind genetic modifiers of apoptosis can aid in the development of diagnostics and therapeutic targets that can overcome the difficulties associated with the treatment of these heterogeneous diseases.</p>