Identification and characterization of tumor suppressor gon-14 gene in C.briggsae Multivulva mutants

Biological Sciences (The Ohio State University Denman Undergraduate Research Forum)This project uses nematodes C. elegans and C. briggsae as experimental systems to identify new tumor suppressor genes, and to understand how they influence cell signaling and cell division. I aim to characterize the cell signaling features of a C.briggsae tumor-suppressor-like mutant, gon-14. In both species, vulva development is a system in which signals from non-epithelial cells, including LIN-3/EGF and LIN-12/ Notch promote vulva cell fate (Zhang et al. 2007). Within this system mutants that exhibit the Multivulva phenotype are important because they show inappropriate division of vulva cells. Consequently, these mutants identify tumor suppressor genes (Sharanya et al. 2015). Our lab has identified new mutants in C.briggsae that exhibit the Multivulva phenotype and in preliminary results I have found that one of these genes is Cbr-gon-14. In Cel-gon-14 encodes a nuclear protein that influences gonad development, but has only a modest impact on vulva cell development. Thus, we have identified that Cbr-gon-14 is a novel tumor suppressor gene that influences cell division differently in the distinct genetic backgrounds represented by the two species. In previous research I used DNA sequencing methods to determine the DNA mutation associated with Cbr-gon-14 mutants and neither of the two alleles sequenced confer a sterile phenotype. Currently, I am testing that I have the right gene by using RNAi and gene rescue studies. To better understand how this gene influences cell division, I will also evaluate the expression of LAG-2, a ligand of the LIN-12/Notch pathway. I will also test whether the excess cell division is dependent on LIN-12/Notch signaling by doing LAG-2 expression analysis studies and gene knockdown experiments. Finally, I will assess the time and location in which the Cbr-gon-14 is required in vulva development by determining the temperature sensitive period of the gon-14 gene and the cells that require gon-14 activity.Academic Major: Neuroscienc