Molecular Neurobiology

The Molecular Neurobiology Research Group, located at the Max Planck Institute of Psychiatry, is headed by Dr. Damian Refojo. The main goal of the group is try to understand the molecular mechanisms by which different biochemical pathways and gene candidates associated to psychiatric or complex brain disorders affect neuronal development and plasticity.
 
In the recent years we have focused our research interest in the study of pathways and genes belonging to ubiquitin-like pathways (UBLs).
Post-translational modification of proteins by ubiquitin and ubiquitin-like proteins is a critical cellular regulatory mechanism. UBLs include Sumo, Isg-15 and Nedd8 among others. Ubiquitylation and sumoylation are involved in a myriad of neuronal functions: neuronal survival, axonal growth and steering, neurite development, synapse formation and elimination, etc. However, the putative role of other ubiquitin-like proteins on the CNS remains almost completely unknown. This is particularly surprising, for instance, for Nedd8 (neural-precursor cell expressed developmentally down-regulated gene 8) whose neuronal expression in the brain is notably high and developmentally regulated.


Fig.1



Analogous to ubiquitylation, UBL cascades involves three sequential reactions mediated by activating enzimes (E1), conjugating enzymes or E2s and a so far poorly characterized number of E3 ligases.
Meanwhile many neuronal and brain functions have been described for Ubiquitylation and Sumoylation pathways, the role of other UBLs remains almost completely unexplored.


 
In order to explore the role of UBLs in neuronal development and function, the group combines biochemical, molecular biology, mouse genetics and live imaging state of the art techniques in primary neuronal cultures, brain slices and transgenic or conditionally inactivated knockouts mice. Thus, different characteristics of neuronal growth: axon extension and terminal arborization, dendrite development, dendritic spine maturation and synaptogenesis, as well as several aspects of synaptic function: neurotransmitter release, signaling, plasticity, etc, are investigated in cell culture and in vivo systems.