The Kiebler Lab explores how individual synapses, the point of contact and communication between neurons, are altered during their lifetime and how this contributes to our ability to learn and remember. As a second new focus in collaboration with the Ninkovic lab, we are investigating how RBPs contribute to neurogenesis and reprogramming.
In all processes, RNA-binding proteins (RBPs) play essential roles. We study the localization of mRNAs into dendrites of polarized hippocampal neurons. A set of mRNAs is specifically transported – once exported from the nucleus into the cytoplasm of neurons – with the help of molecular motors along microtubules into processes termed dendrites. These are the receiving units of information in the brain. Upon demand, mRNAs will be translated into proteins that allow to structurally and functionally modify activated synapses. This is thought to be the molecular basis for learning and memory.
We are specifically interested in understanding the role of key RBPs, e.g. Staufen2, Pumilio2, Argonaute, DDX6 and Barentsz amongst others, in dendritic mRNA localization. A second focus is to identify and subsequently study those mRNAs that are transported to synapses, e.g. CaMKIIa (positive control), Rgs4, Calm3 among others. We have reason to believe that defects in dendritic mRNA localization might yield neurological diseases, e.g. spinocerebellar ataxias, epilepsy, Fragile-X-mental retardation.
Experimentally, we work with primary cells with a special emphasis on rodent hippocampal neurons in isolated culture, as well as with mice and rats.