Verena Obermüller
MRC HGU PhD Student
Long lab (joint with Dr Joe Marsh)
Main focus of current work
The transcription factor SOX9 is an important regulator of skeletal development as well as sex determination. Mutations in or near SOX9 most commonly cause campomelic dysplasia (CD), which is a form of skeletal dysplasia that involves bowing of the long bones in the limbs, as well as other skeletal and craniofacial anomalies and frequent autosomal sex reversal. Most pathogenic missense mutations in SOX9 cluster in the DNA-binding HMG domain and can result in a wide range of disorders including CD and several milder conditions that only show isolated symptoms of CD affecting the skeleton, craniofacial development, or sex determination. This range of phenotypes suggests that certain resides are less deleterious to SOX9 binding to DNA and therefore mutations of these residues may have a lesser impact on protein function as a transcriptional regulator. We aim to perform a deep mutational scan of the SOX9 HMG domain to quantify the disruption to DNA-binding of almost all single amino acid variants. To achieve this, we plan to use saturation mutagenesis of the SOX9 HMG domain in combination with a yeast one-hybrid assay.
Biography
After finishing my Undergraduate studies in Computer Science at the University of Vienna, I decided to pursue my interest in Biology and completed my Master´s degree in Quantitative Genetics at the University of Edinburgh. I am currently carrying out my doctoral work at the Institute of Genetics and Cancer on the MRC-funded PhD programme in Human Genetics, Genomics and Disease.