Theres Eva Friesacher, MSc


Thesis title: "Novel approaches to investigate the regulation of G-protein coupled inward rectifier K+ channels by Gβγ"

Thesis outline: G protein-coupled inward-rectifier potassium channels (GIRK2) are essential regulators of neuronal excitability. They belong to the family of inward-rectifier potassium (Kir) channels, which are generally activated by phosphatidylinositol-4,5- bisphosphate (PIP2). Importantly, GIRKs are unique among Kir channels in that they are regulated by the G-protein βγ (Gβγ) subunit. Additional mediators include Na+, ions and alcohol. Mutations in or close to the selectivity filter of GIRK2 lead to a rare neurological condition called the Keppen-Lubinsky syndrome (KPLBS).

During my PhD, I will use classical and coarse-grained MD simulations to look into the allosteric mechanism underlying GIRK2 channel regulation by Gβγ. Furthermore, I will investigate the consequences of KPLBS inducing GIRK2 mutations in the context of selectivity and channel dynamics. Last but not least, I will explore possible ways for treating KPLBS symptoms and other diseases associated with a malfunctioning of GIRK channels.

Funding: DOC fellowship of the Austrian academy of Sciences (ÖAW) - 26156
Doctoral program "Molecular drug targets" (MolTag) - W1232

Supervisor & Co-Mentors: Anna Weinzinger, Nathan Dascal, Leticia Gonzalez