A UCC researcher has developed a way of watching individual mouse brain cells that will help us understand the processes of the human brain, writes Dick Ahlstrom
A RESEARCHER IN Cork has found a way to locate the elusive needle in a haystack. He can now look at an individual brain cell, watch how it works and study how it responds to specific changes, even as they are taking place.
Dr Paul Young leads the research in the Biochemistry Department and is a member of the Cork Neuroscience Group based in the Biosciences Institute at University College Cork. "It is a technique to study the function of genes in the brains of mice," he explains.
It allows him to label individual brain cells or neurons and then to manipulate them by switching on or switching off specific genes, a process that allows him to identify the function associated with the gene.
He developed the labelling aspect of the process while a post-doctoral research fellow at Duke University in the US, working under Prof Guoping Feng.
He has refined the technique after his return to Ireland and he can now manipulate individual genes in individual, fully functional brain cells.
The technique is Slick by name and slick by nature. Slick is far simpler than its full name, Single-neuron Labelling with Inducible Cre-mediated Knockout. Whatever the name the method is extremely powerful for understanding the complex biochemistry of the brain.
For this reason a research paper on the technique by Dr Young and colleagues featured this month in the online version of the journal Nature Neuroscience. It also takes pride of place as the cover story in the June issue of the print version.
The mice in question are transgenic and carry an extra gene that fluoresces, he explains. Only a small number of the brain cells fluoresce so they stand out and are easily located among the billions of others in the mouse's brain.
Knocking out a gene to study its function is not new and has been used in specific tissues, but Dr Young's Slick technique goes farther. "I am going from a tissue specific knockout to a single cell knock-out," he explains.
"By knocking out a gene you can see what happens to the cell without that gene, how the neuron connects with others around it."
The brain is staggeringly complex with one neuron connected to those around it via cellular connections called dendrites. Many diseases of the brain affect the way these connections are made and maintained, so a deeper understanding of the biochemistry of individual genes should be very valuable in the study of human disease, he suggests.
"You can look at the function of genes and you can also look at the function of genes in disease. [Slick] is a very precise way of doing this."
Dr Young refined and characterised Slick with funding from Science Foundation Ireland and from the department ofbiochemistry.
"The next step is to apply the technique. The thing I want to use it for is looking at genes involved in Alzheimer's disease and try to understand their function," he says. "This system will allow you to look at the cells in a living animal."
The university acquired a "two-photon imager", a highly sensitive form of microscopy that can acquire images deep in the brain and to a very high resolution. The purchase was made using funding from the Programme for Research in Third Level Institutions.
The device will allow Dr Young and his team to see "before and after" images of a manipulated brain cell as it responds to a gene knock-out.
The work is applicable to Alzheimer's disease but also to other forms of dementia and to epilepsy. Many of these diseases are associated with defects in neuronal shape and connectivity between neurons.
Early work using the technique will involve studying a collection of the genes known to have a direct association with these diseases to better understand the related biochemistry.