Investigating CSL Protein Point Mutations That Are Associated With Adams-Oliver Syndrome
Start Date
April 2024
Location
2nd floor - Library
Abstract
Adams-Oliver Syndrome (AOS) is a rare multiple-malformation genetic disorder which is characterized by scalp, cranium, and transverse limb developmental defects. Several point mutations within the CSL transcription factor protein of the Notch signaling pathway have been associated with AOS. CSL can bind to DNA and transcriptional corepressor/coactivator proteins. Of the AOS-associated CSL point mutations tested, all have shown a significant reduction in DNA binding affinity while having no effect on CSL binding affinity to corepressors or coactivators. The following "); border-bottom-width: 1px; border-bottom-style: solid; border-bottom-color: transparent; background-size: 5px auto; vertical-align: -0.003544px; line-height: 0px; position: relative; -webkit-nbsp-mode: normal !important;">three point mutations in CSL still need to be characterized: Y60C, R65G, and S332R. The goal of this research project is to purify each of these CSL variants, and then perform binding assays such as electrophoretic mobility shift assays (EMSA), thermal shift assays, and isothermal titration calorimetry (ITC).
Investigating CSL Protein Point Mutations That Are Associated With Adams-Oliver Syndrome
2nd floor - Library
Adams-Oliver Syndrome (AOS) is a rare multiple-malformation genetic disorder which is characterized by scalp, cranium, and transverse limb developmental defects. Several point mutations within the CSL transcription factor protein of the Notch signaling pathway have been associated with AOS. CSL can bind to DNA and transcriptional corepressor/coactivator proteins. Of the AOS-associated CSL point mutations tested, all have shown a significant reduction in DNA binding affinity while having no effect on CSL binding affinity to corepressors or coactivators. The following "); border-bottom-width: 1px; border-bottom-style: solid; border-bottom-color: transparent; background-size: 5px auto; vertical-align: -0.003544px; line-height: 0px; position: relative; -webkit-nbsp-mode: normal !important;">three point mutations in CSL still need to be characterized: Y60C, R65G, and S332R. The goal of this research project is to purify each of these CSL variants, and then perform binding assays such as electrophoretic mobility shift assays (EMSA), thermal shift assays, and isothermal titration calorimetry (ITC).
