DE NOVO SYNTHESIS OF NAD+ CONRTIBUTES TO REPRODUCTIVE DEVELOPMENT IN CAENORHABDITIS ELEGANS
Open Access
- Author:
- Holleran, Lauren Michelle
- Area of Honors:
- Biochemistry and Molecular Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Dr. Wendy Hanna-Rose, Thesis Supervisor
Dr. Teh-hui Kao, Thesis Honors Advisor
Scott Brian Selleck, Faculty Reader - Keywords:
- NAD+
C. elegans
de novo pathway
reproductive development
gonad delay
brood size
umps-1 - Abstract:
- NAD+ is a molecule that is crucial in many different biochemical pathways across all organisms as an electron transporter. NAD+ also interacts with other proteins, such as sirtuins, which have been linked to aging and stress. In Caenorhabditis elegans, there are three biosynthetic pathways of NAD+, but my focus will be on a newly discovered pathway present in C. elegans, the de novo pathway. In this study, I will show through manipulation of this pathway that it contributes to reproductive development in C. elegans. In previous studies, it has been shown that blocking the salvage pathway of NAD+ synthesis with pnc-1 mutants results in a gonad delay phenotype. I have found that when knocking out both the de novo and salvage pathways with a umps-1;pnc-1 double mutant, the gonad delay phenotype is more penetrant. In pnc-1 mutants, supplementation with quinolinic acid (QA), a metabolite in the de novo pathway, has been shown to reverse the phenotype by increasing NAD+ levels. I show that supplementing umps-1;pnc-1 worms with QA does not fully reverse the phenotype since umps-1 is required to metabolize QA. In addition to the gonad delay phenotype, I focused on brood size, the number of progeny a single worm has, as an indicator of reproductive development. Also in the de novo pathway, kynu-1 mutants have a lower brood size than wild type. I show that supplementation of kynu-1 mutants with QA rescues the lowered brood size phenotype. I also supplement with nicotinic acid (NA), a metabolite in the salvage pathway. NA most likely increases NAD+, which partially reverses the NAD+-dependent phenotype.