Understanding neuron connectivity in health and disease

The ability to think, move, or sense the environment depends on the correct formation and subtle changes of neuronal circuits and their billions of connections. In essence, this connectivity is dependent on neuronal polarization, a process by which neurons develop a long axon and multiple dendrites.
The regulation of axonal growth presents the neuron with important logistical problems derived from the fact that axons can travel great distances to find their targets. In this context, understanding the local processes that affect axon function and physiology is of crucial importance. For example, the concept of axonal mRNA localization and regulated translation at developing axon growth cones and synapses has gained increased acceptance. Our recent work has discovered how small non-coding RNAs (microRNAs) can control the local translation in the axon of key components of the cytoskeleton and thus regulate axonal growth and branching. This work has been followed by studies demonstrating how the local degradation of key proteins in the axon can also play a fundamental role in the regulation of neuron connectivity.

Our lab uses state of the art neuronal culture techniques using compartmentalized microfluidic cultures to model neuron connectivity using cortical and dorsal root ganglia neurons. These microfluidic chambers have allowed us to determine the microRNA content of the axon using next-generation sequencing. The aim of this research project is to identify the cellular function of some of these newly identified axonal microRNAs in health and disease, providing training in general cell biology skills, neuron primary cultures, microfluidic devices, imaging techniques and bioinformatics. We believe this is an exciting and novel project that will address a crucial scientific question in the field of molecular neuroscience.

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