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Daniel Ferris, Sophia Landaeta and Rachel Swope take 3rd Place in the Undergraduate Research Exhibition, Health and Life Science Category

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“Investigating Axonal Neuroprotection and Dendritic Response to Injury in Drosphila Neurons”

 

Nerve cells (neurons) are among the most critical cells in our bodies. Without them we could not talk, walk, see, hear, or think!  Although they are among the most critical of cells most neurons do not divide, meaning that the neurons we have now are the same ones we will have for the rest of our lives. Since neurons must last our entire lifetime, despite possibly sustaining injuries throughout, they have evolved robust mechanism for responding to injuries and regenerating processes including the axon (the process that sends signals) and the dendrites (the processes that receive signals). In scenarios, where a patient has had a stroke or traumatic brain injury, dendrite regeneration becomes important, whereas axon regeneration is relevant in damage to the peripheral nervous system (everything but the brain and spinal cord).

Ferris, Landaeta & Swope

The research being conducted by Rachel Swope (freshman), Sophia Landaeta (freshman) and Daniel Ferriss (sophomore) aims to fill in some of the gaps in our understanding of how nerve cells respond to injury. The signaling pathway that causes axons to regenerate (called the DLK pathway) has been very well studied and characterized; however, the pathway for dendrite regeneration is largely unknown and has been poorly studied.

In attempt to begin to uncover this pathway, Swope used Drosophila (fruit fly) genetics to make flies express fluorophore-tagged proteins of interest (so to visualize these proteins in neurons within Drosophila larvae using confocal microscopy, in vivo) so that she could see expression levels of these proteins before injury and sometime following an injury to the nerve cell’s dendrite using a UV pulse laser. Thus far, none of the proteins tested have shown significant changes in their expression (either increase or decrease) so she continues testing others.

The research group also wanted to come up with a tool to visualize levels of cyclic AMP in neurons (since cAMP is upstream of the DLK pathway for axon regeneration), so Landaeta tested the Flamindo construct: flies that have genes that code for a protein that changes shape when it binds to cAMP, and thus changes its fluorescence. Landaeta successfully used this to show a cAMP increase following axon injury and can now apply it to looking at other types of injuries such as explosion cuts (more severe, heat intensive injury) and dendrite injury.

Lastly, after the axon of a neuron is injured, that neuron goes through something called "neuroprotection". This is a way for the neuron to stabilize itself from further injury.  The cell stabilizes itself through increased microtubules in the dendrites of the cell.  Microtubules are long protein chains which are like the railroads of the cell, moving things back and forth. They also provide strength against mechanical stress, which is what they do in neuroprotection. Ferriss’ research sought to determine whether a certain protein pathway, known as the JAK/STAT pathway, is involved in the mechanism that allows neuroprotection to take place.  Ferriss asked "Is the JAK/STAT pathway responsible for the increased microtubules that exist in the dendrites after axon injury?" Research is still being conducted, but Ferriss has data that suggests it is.  The group is continuing their research and hopes that it will lead to continued understanding of neurons and their response to injury