Wissinger Lab

Molecular Genetics Laboratory

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Julia Stolz

First nameJulia
Position and TitlePhD student, MSc
ProjectFunctional characterization of ATF6

Business address

Molecular Genetics Laboratory
Institute for Ophthalmic Research
Centre for Ophthalmology,
University of Tübingen
Elfriede-Aulhorn-Strasse 7
D-72076 Tübingen,

Phone: +49 (0)7071 29-87619

E-mail: julia.stolz[at]med.uni-tuebingen.de

Project descriptions

Exome sequencing combined with homozygosity mapping in a family with three patients affected by achromatopsia revealed a homozygous missense mutation in ATF6 – the gene encoding the Activating Transcription Factor 6 (ATF6), a key regulator of the UPR and cellular ER homeostasis.

In principle, ATF6 becomes activated by ER stress which emerges out of unfolded or misfolded protein accumulation. In its activated form ATF6 is then responsible for the transcriptional regulation of genes responsible for apoptosis, removal of unfolded proteins and chaperons. Since ATF6 is expressed ubiquitously, it is striking that patients harboring mutations in the ATF6 gene show only a complete loss of cone photoreceptor function under photopic vision without any abnormalities in the rod photoreceptor function under scotopic vision.

Generally, the UPR has not been analyzed in many models for hereditary retinal disease. Indeed, recent studies could demonstrate that mutations in photoreceptor genes result in an activation of the UPR, probably because of misfolded mutant proteins, and this plays a role in the retinal degenerative processes.

My project will try to assess the expression, function and malfunction of ATF6 caused by the mutations observed by means of immunohistochemistry and functional studies in patient derived cell cultures harboring the observed mutations as well as heterologous expression systems. In addition we are interested to study those questions also in appropriate animal models. Therefore we will try to generate a zebrafish atf6 -/- line using the TALEN and/or CRISPR/Cas System. As a second animal for the functional characterization of ATF6 we will use the Atf6 -/- knockout mouse which is already available in our laboratory.