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NatWi - Tanja Vogel

Prof. Dr. Tanja Vogel

Lebenswissenschaften, Neuroentwicklungsepigenetik
Albert-Ludwigs-Universität Freiburg

Generating isogenic iPS-cell lines carrying different FOXG1 gene mutation for studying molecular causes of FOXG1-related syndrome
Wann 03.11.2020
von 11:30 bis 12:30
Wo Zoom-Meeting
Name
Teilnehmer universitätsoffen / open for university members
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Generating isogenic iPS-cell lines carrying different FOXG1 gene mutation for studying molecular causes of FOXG1-related syndrome

FOXG1-related syndrome is a severe neurodevelopmental disease. Options for therapy of this debilitating disease are sparse because of variability of genotype-phenotype relations. To overcome limits in therapy we need to understand the molecular basis of the disease. FOXG1 is a transcription factor that is indispensable for development of the forebrain. However, its plethora of molecular functions are only emerging. In the proposed research, I aim to generate human cell model systems to study molecular alterations caused by specific mutations of FOXG1. CRISPR/Cas9 technology will be used to introduce point mutations, described in human patients presenting with FOXG1-related syndrome, in human induced pluripotent stem cells (iPSC). I plan to generate five different cell lines using the same parent iPSC to study the effect of specific mutations within the same genetic background of the parent cell line. Such set-up is of importance, as variation in the genetic background can disguise or overemphasize specific molecular alterations. As our set of cell lines will be constructed under standardized conditions emerging data sets will not have shortcomings due to different handling or origin of iPSC. Whereas the main focus of this application is the generation of the different iPSC, subsequent experiments will enlighten the molecular alterations caused by FOXG1 mutation. Following our preliminary data from the mouse, experiments will reveal epigenetic alterations including histone modifications and dynamic changes of the chromatin structure, in combination with transcriptomic analysis. The latter should occur in organoids that derive from the iPSC that I am planning to generate in this project, followed by single-cell RNA sequencing