Midway evaluation in Biology - Kristín Elísabet Allison

Event on Zoom

Title: Molecular and cell biological causes of neurological symptoms in CTD

Doctoral candidate: Kristín Elísabet Allison

Doctoral committee:
Sigríður Rut Franzdóttir, Associate professor at the Faculty of Life and Environmental Sciences, University of Iceland
Guðmundur Logi Norðdahl, Head of Functional Genomics, DeCODE genetics
Ragnhildur Þóra Káradóttir, Professor at the Faculty of Medicine, University of Iceland
Zophonías O. Jónsson, Professor at the Faculty of Life and Environmental Sciences, University of Iceland

Abstract

Citrate transporter disorder (CTD) is a severe neurological disorder caused by recessive mutations in the SLC13A5 gene. The gene encodes a sodium-coupled citrate transporter (NaCT), the orthologue of which can be knocked out in experimental animals without deleterious neurological effects. In humans however, mutations result in severe epilepsy, ataxia, hypotonia and lack of speech, highlighting the need for a human based CTD model system. A disease variant in SLC13A5 was found to be 25-50x more common in the Icelandic population than in Europe in general, prompting this research project to be initiated.
Little data exists on the role of citrate and citrate transport in the brain and is mostly limited to rodent experiments published over 20 years ago. The first goal of this project was therefore to examine where in the healthy human brain NaCT can be found. The information from this expression analysis will be used to set up induced pluripotent stem cell (iPSC) derived cell culture models for CTD.
In the talk Kristín will cover the theoretical background of the project, the generation of the model system and discuss preliminary findings.