Discipline: Biological Sciences
Room: Exhibit Hall A
Sanika Pandit - Chapman University
Co-Author(s): Rebekah Townsley, University of Arkansas; Emmanuel Taduidje, Department of Biological Sciences, Alabama State University, Montgomery, AL, Center for NanoBiotechnology Research, Alabama State University, Montgomery, AL
Cholesterol is an essential molecule in the cell that regulates hormone synthesis, influences membrane permeability and fluidity, modulates transmembrane signaling, and maintains homeostasis. While high cholesterol plagues many Americans annually, hypercholesterolemia drugs are rarely prescribed to pregnant women as these drugs cause serious birth defects. Typically, statins and competitive inhibitors prevent the synthesis of cholesterol along its two synthesis pathways. In this project, we studied how blocking the biosynthesis of cholesterol, proximally using Lovastatin and distally using AY9944, along the Kandutsch-Russell pathway affects development. For each experiment, Xenopus laevis embryos were generated via invitro fertilization, grown to the blastula stage, and then treated with varying concentration of either Lovastatin or AY9944. Through our studies, we observed that concentrations of Lovastatin caused pericardial edemas, shortened body axes, and severe developmental delay, while AY9944 showed no severe change. Additionally, explant treatments were done to understand the effect of the inhibitors on mesoderm extension. Marginal zones were solely treated with inhibitors; animal caps were treated with inhibitors and Activin, to induce mesodermal growth. In both studies the explants failed to elongate in the Lovastatin treatment. However, AY9944 treated animal caps showed minute abnormal elongation. Through the embryo and explant studies, it was evident that Lovastatin impacts the TGF-B signaling pathway, as this pathway controls body axis elongation. Furthermore, embryo mortality was seen to have significantly increased by the tadpole stage in Lovastatin. These results confirm that cholesterol biosynthesis inhibitors are indeed toxic to development and may cause embryo mortality. However, more studies are needed in order to determine what genes and signaling pathways are specifically being affected.
Funder Acknowledgement(s): This work was supported by NSF-REU (DBI-1659166) to Dr. Komal Vig (PI); This work was supported by NSFCREST (HRD-1241701) to Dr. Shree S. Singh (PI).
Faculty Advisor: Emmanuel Tadjuidje, firstname.lastname@example.org
Role: For this project, I did all of the in vitro fertilizations, as well as all of the treatments with the chemical inhibitors. Along with the background research, I did all of the data analysis and molecular biology work as well.