Molecular Neurobiology

The Molecular Neurobiology Research Group, located at the IBioBA-Max Planck Partner Institute of Buenos Aires, is headed by Dr. Damian Refojo. The main goal of the group is try to understand the molecular mechanisms by which different non-canonical biochemical pathways and gene candidates associated to psychiatric or complex brain disorders affect neuronal development, plasticity and behavior.

Synapses are specialized junctions operated by highly complex protein-based molecular machineries whose composition and functional dynamics is tightly controlled by several post-translational modifications. Ubiquitin and Ubiquitin-like proteins (UBLs) like Sumo, ISG15 and Nedd8 among others, decisively control neuronal protein localization, interaction, turnover and activity, thereby regulating different aspects of dendritic and synaptic function. However, the role of other Ubiquitin-like proteins remains almost completely unknown. Our group has recently demonstrated that Nedd8, a UBL considered to be mostly linked to cell cycle and cell proliferation, is highly expressed in neurons and controls synaptic development and maintenance. One of the main goals of the Molecular Neurobiology Group is to disentangle the role of Neddylation, in neuronal development and synaptic function and its impact on emotional and cognitive behaviors.

Non-coding RNAs, including microRNAs and circular RNAs, add another layer of complexity to the posttranscriptional regulation of protein function and synthesis on local dendritic and axonal microcompartments. We are also interested in the identification and characterization of novel non-coding RNAs with relevant roles in dendritic and synaptic development and function.

 

 

The main research goal of our group is focused on two non-cannonical cell pathway systems, on different aspects of neuronal development, plasticity and function both in cell culture and in vivo systems. Currently our main focus is the role of the Nedd8 conjugation pathway axonal and dendritic differentiation and the expression and function of CircRNAs in neurons.

The mechanistic bases of psychiatric disorders like depression and anxiety remain unknown. Although they can be considered as disorders of the neural communication and information processing, the influence of synaptic proteins on the onset and evolution of mood disorders has not been intensively studied. In this context the third goal of our research group is the identification of synaptic molecules involved in signaling and plasticity that can help explaining the molecular bases of these psychiatric syndromes.

In order to pursue these goals, 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 knockout mice. Thus, different characteristics of neuronal growth (axon extension and terminal arborization, dendrite development, dendritic spine maturation and synaptogenesis), synaptic function (neurotransmitter release, signaling, plasticity, etc) and mouse behavior, are investigated in cell culture and in vivo systems.