cool science

Nerve cell communication mechanisms uncovered, may lead to new therapeutic approaches for neurodegenerative diseases

 

Story by Madison Knapp/ Bond Life Sciences summer intern

Simple actions like walking, swallowing and breathing are the result of a complex communication system between cells. When we touch something hot, our nerve cells tell us to take our hand off the object.

This happens in a matter of milliseconds.

This hyperspeed of communication is instrumental in maintaining proper muscle function. Many degenerative diseases affecting millions of people worldwide result from reduced signaling speed or other cellular miscommunications within this intricate network.

Michael Garcia, investigator at the Christopher S. Bond Life Sciences Center and associate professor of biology at the University of Missouri, conducts basic research to answer fundamental questions of nerve cell mechanics.

“In order to fix something, you need to first understand how it works,” Garcia said.

Garcia’s research illuminates relationships between nerve cells to find factors affecting function.  His goal is to provide insight on fundamental cellular mechanisms that aren’t fully understood.

Garcia’s research has been funded partly by the National Science Foundation and National Institutes of Health.

Technological advancements have made it possible to better understand disease development in the human body to create more effective treatments. Alas, a scientist’s work is never finished— when the answer to one question is found, ten more crop up in its wake.

Garcia’s research, which appeared in several journals including Human Molecular Genetics andthe Journal of Neuroscience Research initially sought to shed light on the neuronal response to myelination, the development of an insulating border around a nerve cell, called a myelin sheath, which is critical in rapid communication between cells.

Eric Villalon, a graduate student in Michael Garcia's lab at the Bond Life Sciences Center, examines results. The Garcia Lab is answering news questions in cell mechanics. | PAIGE BLANKENBUEHLER

Eric Villalon, a graduate student in Michael Garcia’s lab at the Bond Life Sciences Center, examines results. The Garcia Lab is answering news questions in cell mechanics. | PAIGE BLANKENBUEHLER

How it works: Rebuilding cell theory

Garcia’s early research disproved a long-standing hypothesis concerning this cellular feature.

Mammals’ nervous systems are uniquely equipped with myelination, which has been shown to increase conduction velocity, or the speed at which nerve cells pass signals. Low velocity is often associated with neurodegenerative diseases, so research exploring why could later have application in therapeutic technology.

In addition to myelination, cell size makes a big difference in conduction velocity — the bigger the nerve cells, the faster they can pass and receive signals. Garcia’s findings disproved a hypothesis that related myelination to this phenomenon.

The hypothesis, published in a 1992 edition of Cell, claimed that myelination causes a cellular process called phosphorylation which then causes an increase in the axonal diameter (width of the communicating part of a nerve cell), leading to faster nerve cell communication. Garcia found that myelination did cause an increase in axonal diameter, and myelination was required for phosphorylation, but that the two results were independent of one another.

To narrow in on the processes affecting axonal diameter, Garcia identified the protein responsible for growth.

Garcia followed earlier work, showing that one subunit controls whether there is growth at all with myelination, by identifying the domain of this protein that determines how much growth.

After clarifying this part of the process, a question still remains: If not to control myelination, why does phosphorylation happen?

 

Looking forward

Jeffrey Dale, a recent PhD graduate from Garcia’s lab, said current research is in part geared toward finding a connection between phosphorylation and a process called remyelination.

Remyelination could be key to new therapeutic approaches. When a cell is damaged (as in neurodegenerative disease) the myelin sheath can be stripped away. Remyelination is the process a cell goes through to replace the myelin.

Imagine you have a new wooden toy boat, painted and smooth. If you take a knife and whittle away all the paint and then repaint it—even exactly how it was painted before—the boat is not going to be as shiny and smooth as it was before. This is how remyelination works (or rather, doesn’t).  When nerve cells are damaged, the myelin sheath is stripped away and even after the cell rebuilds it, the cell can’t conduct signals at the same speed it was able to before.

“If you can learn what controls myelination, maybe you can improve effectiveness of remyelination,” Dale said.

Garcia said it is possible that revealing the mechanics involved in phosphorylation could lead to better treatments. In context of neurodegenerative diseases, the question why don’t axons function properly might be wrapped up in Garcia’s question: In healthy cells, why do they?

Supervising editor: Paige Blankenbuehler

New screening tool gives scientists more control over genetic research

A tangled spool of yarn represents DNA, while the fingers holding the section represent the insulators just added by MU researchers to improve a scientific, screening tool. | Paige Blankenbuehler

A tangled spool of yarn represents DNA, while the fingers holding the section represent the insulators just added by MU researchers to improve a scientific, screening tool. | Paige Blankenbuehler

Here’s a scenario: You are trying to find a lost section of string in the world’s most massively tangled spool of yarn. Then try cutting that section of yarn that’s deeply embedded in the mess without inadvertently cutting another or losing track of the piece you’re after.

For researchers, this problem is not unlike something they encounter in the study of genetic information in the tangled spool that is DNA.

A new tool will help scientists straighten things out.

The tool, developed by University of Missouri Bond Life Sciences Center investigators helps researchers effectively screen cell behavior by limiting epigenetic silencing, which occurs when a cell packages and stows away important genetic information, much like an accountant puts a client’s information away in a filing cabinet.

The cell can go digging to find that information when it absolutely needs it, but otherwise that information is tucked away and inactive.

Professors of biochemistry Mark Hannink, Tom Mawhinney and research assistant professor Valeri V. Mossine used insulators to develop the piggyBac transposon plus insulators, a better reporter of signaling between cells that makes improved screening possible.

This simple addition to an existing screening tool used in laboratories will help streamline research and contribute to screening products like vitamins and supplements and medicines for authenticity, Hannink said.

This is why the insulator addition to the piggyBac reporter assay by MU researchers is a game changer in the scientific world.

 

How it works

DNA stretches out to nearly 10 feet when it’s uncoiled. That’s 10 feet of your body’s deepest secrets coiled into a microscopic package and tucked away into each and every one of your cells. The human body, by the way, holds an estimated 10 trillion cells. An inconceivable number, right?

Let’s go back to our yarn analogy. You’re trying to find one specific piece to cut but it’s deeply tangled in the mass of yarn. You need to find the piece that you really care about and clamp your fingers onto the yarn to reduce the slack — straighten it out — so you can cut it easily.

Think of your fingers as the insulators.

The insulators of the new piggyBac transposon tool perform the same task of stretching out the DNA so certain expressions through signaling pathways are held open, enabling the investigation of specific genetic material.

Hannink hypothesizes this new reporter could provide answers to questions like: Does an anti-migraine medicine have the component that will relieve that ailment? Does a multi-vitamin deliver all of the nutrients on its label?

“A lot of botanicals are said to have anti-inflammatory benefits,” Hannink said. “By using an assay like this, we can easily determine if they actually do and if so, what molecules in these complex mixtures are in fact the cause of the punitive inflammatory activity.”

 

 

Reproducing results

Replication is a critical part of verifying scientific discovery and epigenetic silencing is a big headache for investigators trying to reproduce results.

Scientists studying genetic material can open certain expressions with other reporter tools but often, the cell will turn expressions off and block signaling pathways, causing an expected result to fail because of epigenetic silencing.

The new assay preserves conditions of an experiment so the same results can be reached. Cell behavior under the same conditions and expressions that were switched on during the experiment will be expressed.

The new version of the reporter assay is being used at the MU Center for Botanical Interaction Studies to understand how botanical compounds affect the immune system and in other research on the central nervous system and on the development of prostate cancer.

This research appeared in the Dec. 20, 2013 edition of PLoS ONE. It was funded by the University of Missouri Agriculture Experiment Station Laboratories and grants from the National Center for Complementary and Alternative Medicines, Office of Dietary Supplements and the National Cancer Institute.