As a postdoctoral fellow in the Yoder Lab at the University of Alabama at Birmingham, I revived the lab's work using C. elegans as model to study novel genes and genetic interations required for primary cilia formation and function. Primary cilia are critical sensing and signaling hubs that extend from nearly all mammalian cell types. In C. elegans, primary cilia are found on a specific subset of cells, the sensory neurons.
More recently, the Yoder lab has also branched into the development of patient-guided models for rare diseases in C. elegans.
I have led a team of undergraduates and technicians in our work on three main projects:
Characterizing the genetic interaction between bbs-5 and nphp-4
Ciliopathies are a spectrum of human disorders associated with defects in cilia formation and function that result in a wide and variable range of clinical features, often with low genotype to phenotype correlation. This phenotypic variability may stem from the presence of multiple modifier alleles causing different degrees of primary cilia dysfunction. To identify modifier alleles, we conducted a mutagenesis screen in C. elegans with a primary mutation in the ciliary transition zone component nphp-4 and looked for secondary mutations that caused ciliary dysfunction. From this screen, we identified a mutation in the BBSome component bbs-5 as a genetic modifier of the phenotype in nphp-4 mutants. I am now working on characterizing how this genetic interaction affects primary cilia function in C. elegans. In addition, through collaborations with fellow Yoder lab graduate student Melissa Bentley and the Parant Lab at UAB, we are determining whether this genetic interaction is conserved in both zebrafish and mice.
Identifying novel genetic interactions with mks-1
Mutations in another transition zone component, MKS1, are associated with multiple human ciliopathies that also present with low genotype to phenotype correlation. Therefore, as a follow up to our nphp-4 mutagenesis screen, I led a second mutagenesis screen in C. elegans to identify modifier alleles in animals harboring a mutation in mks-1. I have identified 24 unique strains that pass non-lethal dye filling defects on to their progeny. To determine the loci associated with the dye filling defects in each strain, I am collaborating with the Lasseigne Lab at UAB to employ a mapping by sequencing technique.
Using C. elegans to develop models of rare diseases for drug discovery
The overall functional conservation between humans and C.elegans covers nearly 70% of protein-coding genes. This makes C. elegans a highly tractable and cost-effective model in which to develop patient-guided models for rare human diseases.