Biology's 'breadboard': cGAL, a temperature-robust GAL4-UAS system for C. elegans

December 26, 2016
The roundworm C. elegans, measuring a mere 1 millimeter, is a powerful model system for understanding how nervous systems produce behaviors. Credit: Navin Pokala

The human brain, the most complex object in the universe, has 86 billion neurons with trillions of yet-unmapped connections. Understanding how it generates behavior is a problem that has beguiled humankind for millennia, and is critical for developing effective therapies for the psychiatric disorders that incur heavy costs on individuals and on society. The roundworm C elegans, measuring a mere 1 millimeter, is a powerful model system for understanding how nervous systems produce behaviors. Unlike the human brain, it has only 302 neurons, and has completely mapped neural wiring of 6,000 connections, making it the closest thing to a computer circuit board in biology. Despite its relative simplicity, the roundworm exhibits behaviors ranging from simple reflexes to the more complex, such as searching for food when hungry, learning to avoid food that previously made it ill, and social behavior.

Understanding how this dramatically simpler works will give insights into how our vastly more complex brains function and is the subject of a paper published on December 26, 2016, in Nature Methods.

Specifically, in electrical and computer engineering, circuits are designed and studied using breadboards that allow circuit elements to be easily added, removed, and modified. Likewise, in order to understand how the neural circuits in brains generate behavior, scientists need to manipulate the activity of , turning them on and off at will. To do this, researchers have developed robust tools (transgenic actuators), that use drugs or light to activate or silence the neurons in which they are expressed. At present, these cell-specific systems need to be custom-made for each neuron and actuator combination a researcher may be interested in.

Navin Pokala, Ph.D., assistant professor of Life Sciences at New York Institute of Technology (NYIT) College of Arts and Sciences, with researchers at Caltech, adapted the GAL4-UAS system for expressing transgenes in the nematode C elegans. This system, which uses a gene regulatory protein from yeast, greatly reduces the work required for making cell-specific perturbations. Instead of constructing new DNA and transgenic animals for each cell and actuator, new cell-actuator combinations can be generated by simply mating already-constructed animals, dramatically reducing the time and cost.

Pokala and his collaborators plan on exploring variations to the GAL4-UAS system that allow more precise control of actuator gene expression than is currently possible. The newfound ease of transgenic animal construction allows for systematic perturbation of the cells in the nervous system, allowing Pokala and colleagues to build a database linking neural perturbations to behaviors. When combined with the previously mapped circuit wiring, this database will be a valuable resource for developing and testing models of nervous system function.

Explore further: Researchers provide first peek at how neurons multitask

More information: Han Wang et al, cGAL, a temperature-robust GAL4–UAS system for Caenorhabditis elegans, Nature Methods (2016). DOI: 10.1038/nmeth.4109

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BubbaNicholson
1 / 5 (2) Dec 26, 2016
Control of psychiatric illness can be accomplished with human pheromones alone. A paternal facial skin surface lipid pheromone deficiency (not kissing one's father sufficiently in childhood) originates all (so far as has been tested) human sociopathy. The gamut runs from criminal behavior & drug addiction to ADHD, PTSD, OCD, onychophagia and sexual perversions. Isolation of pheromone treated patients and recognizing the extreme biohazard of collected pheromone airborne emissions are all that's needed for great advances.
These worms of Kandel et al. are worthless so far as our understanding human behavior. Myelination, the white matter of the brain is where switching takes place, via shared capacitance switching. Schwanns/oligodendrites are always exactly the same wrap size on a neuron because total capacitance is the sum of the inverses of individual capacitors, so it is electrically and economically pointless to use serial capacitors of different size on the same circuit.
BubbaNicholson
1 / 5 (2) Dec 27, 2016
Pheromones cause disease, psychiatric and autoimmune. The variety depends upon other pheromone receptions and receptivity. For instance, homosexuality is a paternal facial skin surface lipid pheromone deficiency in the face of a maternal facial skin surface lipid pheromone sufficiency. Proteins dissolved in tears (and blood), pheromone receptor proteins, sequester ions until pheromone-keyed release, changing potential difference, changing voltage, which is detected by the dendrite's voltage gated channels. Receptor proteins are "carrier" proteins, which change conformation on pheromone contact.
MarsBars
1 / 5 (1) Dec 28, 2016
Control of psychiatric illness can be accomplished with human pheromones alone. A paternal facial skin surface lipid pheromone deficiency (not kissing one's father sufficiently in childhood) originates all (so far as has been tested) human sociopathy. The gamut runs from criminal behavior & drug addiction to ADHD, PTSD, OCD, onychophagia and sexual perversions.

... homosexuality is a paternal facial skin surface lipid pheromone deficiency in the face of a maternal facial skin surface lipid pheromone sufficiency.

Bubba, can you cite any peer-reviewed papers or other scientific evidence in support of your extraordinary claims?
BubbaNicholson
1 / 5 (1) Dec 28, 2016
Scurvy was first cured anecdotally. For God's sake, it's the grease on your nose. 10mg will show dramatic therapeutic effect. We did a double blind cross over placebo controlled clinical trial in Egypt for ADHD. ADHD was vanquished, the trial was completely successful so far as the patients were concerned. The PI was nearly fired. The staff threatened a walk out. The kids were fine, the parents were up in arms. There is a national investigation ongoing. I've had the SWAT team come to my house. I've been visited by 8 police forces.
You must, must, must isolate patients. You must, must, must treat collected pheromone as a biohazard.
Nicholson B. Pheromones cause disease: pheromone/odourant transduction.
Med Hypotheses. 2001 Sep;57(3):361-77.
MarsBars
1 / 5 (1) Dec 29, 2016
Bubba, can you cite any peer-reviewed papers or other scientific evidence in support of your extraordinary claims?

Nicholson B. Pheromones cause disease: pheromone/odourant transduction.
Med Hypotheses. 2001 Sep;57(3):361-77.

Apart from your own paper, if you don't mind.
BubbaNicholson
1 / 5 (1) Dec 29, 2016
Read the paper and don't be lazy. Since it's writing, it finally dawned on me that the collected skin surface pheromone was emitting a behavior altering airborne component. Why else should a scientist suffer the interest of 8 different police forces including the local SWAT team? It's face grease, not Trinitrotoluene. It also explains how my colleagues abandon me after I cured their various relatives *with me begging for help with clinical trials, the near firing of my overseas colleague who used the collected skin surface pheromone to cure all his ADHD hospitalized boys, but was threatened with termination, that sort of thing.
If you're really interested, may I suggest you read my book, Exocrinology the Science of Love, 2011 by B. Nicholson on Amazon digital books.

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