Dysferlinopathy's Affect on Aging Muscles in Mice and in C.Elegans Fer-1 Ortholog

Abstract

Muscular Dystrophy is a genetic disease that causes muscle weakness and atrophy over time. I have worked on two projects over two semesters, the first is a bioinformatics project that studied a form of muscular dystrophy, dysferlinopathy, in mice. We wanted to know why certain muscles were affected early on, some were affected during aging, and some were not affected at all. Once we knew which muscles were in those categories, we used a website called Galaxy to analyze RNA sequencing data from those muscles to identify which genes were affected during aging. We focused on the soleus muscle because it was affected most during aging. We compared our Soleus aging RNA sequencing data to other scientist's research who found genes that were differentially expressed in dysferlinopathy patients. We wanted to see if any of these genes changed during aging because this might make the soleus vulnerable to dysferlin loss. Three of these genes were upregulated during aging, and they are all involved in muscle contraction and linked to muscle disease. The genes are NEB, MYH7, and Ttn.

For the second project, I am modeling dysferlinopathy using C. Elegans worms. We're studying the dysferlin ortholog, fer-1. Mutations in Fer-1 result in infertility due to defects in membrane fusion. We will identify genes that rescue infertility using a suppressor screen; UV irradiation to induce mutations and select worms that can produce offspring. These new strains will be isolated and mapped using linkage analysis techniques to determine the identity of the gene.

Madison Russo | Biology and Chemistry | Faculty Sponsor Eric Williams