Seyedeh Parnian Vakili, “Using Caenorhabditis elegans to Test the Impact of Cardiofaciocutaneous Syndrome Mutations”
Mentor: Claire de la Cova, Biological Sciences
Poster #197

Cardiofaciocutaneous (CFC) syndrome and Noonan syndrome (NS) are collectively termed RASopathies, a group of genetic disorders characterized by dysregulation in the RAS signaling pathway. CFC syndrome presents with facial dysmorphisms, short stature, cardiac anomalies, and developmental issues. CFC syndrome is predominantly associated with mutations in the BRAF gene, which encodes a protein kinase that activates the kinases MEK and ERK. BRAF protein contains a regulatory region with a Ras-binding domain and a cysteine-rich domain (CRD), and a catalytic region with a kinase domain. The most common BRAF mutation found in CFC is the missense Q257R, which alters the CRD. The Q257R mutation leads to increased kinase activity, which in turn activates MEK and ERK. Currently, the effects of CFC mutations on BRAF protein levels, localization, and protein interactions are unknown. We previously generated mutations in the Caenorhabditis elegans RAF gene that were modeled after those found in NS. The aim of this project was to examine the molecular consequences of the Q257R CFC syndrome mutation in C. elegans RAF. Our strategy employed CRISPR/Cas9 gene editing to induce mutations in C. elegans that model those observed in human patients. We generated the mutation M194R in the C. elegans RAF gene, which is similar to the Q257R mutation observed in the human BRAF gene. In future studies, we will use these mutants to investigate how RAF protein levels and localization are altered. This work will establish a new mutant model for understanding RAF dysregulation in CFC.