Molecular Robots Can Help Researchers Build More Targeted Therapeutics

All cells possess receptors on their cell surface. Drugs bind to their receptors in order to trigger the cells to perform. Since disease-causing cells' receptors may not have unique receptor compare to the healthy cells it would create a complexity which means the drugs target disease-causing cells as well as healthy cells. To overcome this challenge scientists have designed molecular robots that can identify multiple receptors on cell surfaces, thereby effectively labeling more specific subpopulations of cells. The molecular robots, called molecular automata, are composed of a mixture of antibodies and short strands of DNA (oligonucleotides). The researchers conducted their experiments using white blood cells. All white blood cells have CD45 receptors, but only subsets have other receptors such as CD20, CD3, and CD8. In one experiment, HSS researchers created three different molecular robots. Each one had an antibody component of either CD45, CD3 or CD8 and a DNA component. The DNA components of the robots were created to have a high affinity to the DNA components of another robot. DNA can be thought of as a double stranded helix that contains two strands of coded letters, and certain strands have a higher affinity to particular strands than others. The researchers mixed human blood from healthy donors with their molecular robots. When a molecular robot carrying a CD45 antibody latched on to a CD45 receptor of a cell and a molecular robot carrying a CD3 antibody latched on to a different welcoming receptor of the same cell, the close proximity of the DNA strands from the two robots triggered a cascade reaction, where certain strands were ripped apart and more complementary strands joined together. The result was a unique, single strand of DNA that was displayed only on a cell that had these two receptors. The addition of a molecular robot carrying a CD8 antibody docking on a cell that expressed CD45, CD3 and CD8 caused this strand to grow. The researchers also showed that the strand could be programmed to fluoresce when exposed to a solution. The robots can essentially label a subpopulation of cells allowing for more targeted therapy. The researchers say the use of increasing numbers of molecular robots will allow researchers to zero in on more and more specific subsets of cell populations.

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Switch from conscious to unconscious learning systems

Most students know a thing or two about learning while stressed. New research from Ruhr-University Bochum in Germany found that a certain type of cellular receptor is key to learning under pressure, according to a new study published in Biological Psychiatry. Mineralcorticoid receptors bind to molecules like the stress hormone cortisol. These receptors, the researchers found, signaled a shift from conscious to unconscious learning in people. When these receptors were blocked, individuals were less able to deliberately learn the rules to a weather prediction game. This blockage didn't affect those who were told to go with their gut and figure out the rules. Shifting learning strategies is a fundamental mechanism in adapting to stressful situations, the researchers say.

Read more: http://bit.ly/1bXvuiIJournal article: Mineralocorticoid Receptor Blockade Prevents Stress-Induced Modulation of Multiple Memory Systems in the Human Brain. Biological Psychiatry, 2013. doi:10.1016/j.biopsych.2013.06.001

Speedier scans reveal new distinctions in resting and active brain

Better, faster brain scans are helping scientists get a more accurate picture of how neurons gather together in groups called networks. In a new study published in Neuron, scientists at Washington University in St. Louis used a new technique called magnetoencephalography (MEG, pictured) to watch how neurons communicate with each other. The researchers recorded the brain activity of two groups of people: one who were resting and watching a move, and the other that was instructed to notice specific changes in movie scenery and plot. Changes in movie scenery was associated with specific changes in neural networks in the visual cortex. Whereas fMRI can only record brain activity that cycles once every 10 seconds, MEG can record activity down to 50 cycles each second. This technique will greatly improve our understanding of the brain, researchers say.

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Journal article: Natural Scenes Viewing Alters the Dynamics of Functional Connectivity in the Human Brain. Neuron, 2013. doi: 10.1016/j.neuron.2013.06.022
Image credit: Oxfordjournals

X-chromosome helps produce sperm

The supposedly “female” chromosome may have a very male role after all: mediating male infertility and sperm production. The X is also much more rapidly evolving that previously believed, according to research published this week. The researchers came to these conclusions after re-sequencing the existing human X chromosome assembly and comparing it with the X of the mouse, which revealed that while certain regions were highly genetically similar, many others were not shared—a finding that challenged the long held dogma that X-linked genes vary little among mammals. 

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Lentiviral gene therapy

The latest study indicates that lentiviral gene therapy is a safe and effective approach to treat certain diseases. In this method researchers used lentiviruses base, which they have modified not only to improve the efficiency of gene transfer, but also to avoid the activation of cancer-causing genes by loading the vector with self-inactivating promoter sequences that exclusively induce the expression of the therapeutic gene. The researchers transferred a functional ARSA gene into HSCs taken from nine pre-symptomatic MLD patients. Analyses performed 2 years after treatment with the modified HSCs in one patient, and after 18 months in another two patients, revealed that 45–80 percent of the blood cells carried the functional gene. The enzyme was present at normal, healthy levels in these cells and in the cerebro-spinal fluid, where it was completely lacking before. What’s more, long after the symptoms would usually have manifested, the progression of the disease had been stopped in its tracks.

Read more: http://www.the-scientist.com/?articles.view/articleNo/36481/title/Gene-Therapy-Coming-of-Age-/

Controlling genes with light - MIT News Office

A new technology developed at MIT  the Broad Institute that can rapidly start or halt the expression of any gene of interest simply by shining light on the cells. This technique helps the scientists to understand the function of genes better by taking advantage of CRY2 light-sensitive  protein, which changes its shape and binding to CIB1 in the present of light. 

Read more: http://web.mit.edu/newsoffice/2013/controlling-genes-with-light-0722.html

Researchers show that memories reside in specific brain cells - MIT News Office

MIT researchers used Optogenetics to show that memories really do reside in very specific brain cells, and that simply activating a tiny fraction of brain cells can recall an entire memory.

Read more: http://web.mit.edu/newsoffice/2012/conjuring-memories-artificially-0322.html

Image:  An image of a transgenic mouse hippocampus, Source MIT News 

Changes in Astrocytes Shape Result Brain Damage After Traumatic Brain Injury

Astrocytes are star-shaped glial cells which provide structural and metabolic support to neurons and respond to beneficial and detrimental effects in response to neurological trauma. The current research study at University of Bristol suggests brain injury could trigger shape changes in astrocyte cell cultures by altering the genes that controlled actin, a key component of the cytoskeleton. They also identified as yet unknown proteins that were also important in changing astrocyte shape. Given that these astrocyte changes can be both harmful (by preventing the regeneration of nerve cells) or beneficial (by creating a scar that prevents further damage), researchers say they are only beginning to understand the relationship between astrocytes and traumatic brain injury.
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Journal article: The antagonistic modulation of Arp2/3 activity by N-WASP/WAVE2 and PICK1 defines dynamic changes in astrocyte morphology. Journal of Cell Science, 2013; DOI: 10.1242/jcs.125146

Image: Astrocytes (Blue) and Microglial cells (Red) in hippocampus of the adult rat brain