Lifeboat Foundation

Abstract.

Developmental dyslexia is a common disorder with a strong genetic component, but the underlying molecular mechanisms are still unknown. Several candidate dyslexia-susceptibility genes, including KIAA0319, DYX1C1, and DCDC2, have been identified in humans. RNA interference experiments targeting these genes in rat embryos have shown impairments in neuronal migration, suggesting that defects in radial cortical migration could be involved in the disease mechanism of dyslexia. Here we present the first characterisation of a Kiaa0319 knockout mouse line. Animals lacking KIAA0319 protein do not show anatomical abnormalities in any of the layered structures of the brain. Neurogenesis and radial migration of cortical projection neurons are not altered, and the intrinsic electrophysiological properties of Kiaa0319 -deficient neurons do not differ from those of wild-type neurons. Kiaa0319 overexpression in cortex delays radial migration, but does not affect final neuronal position. However, knockout animals show subtle differences suggesting possible alterations in anxiety-related behaviour and in sensorimotor gating. Our results do not reveal a migration disorder in the mouse model, adding to the body of evidence available for Dcdc2 and Dyx1c1 that, unlike in the rat in utero knockdown models, the dyslexia-susceptibility candidate mouse homolog genes do not play an evident role in neuronal migration. However, KIAA0319 protein expression seems to be restricted to the brain, not only in early developmental stages but also in adult mice, indicative of a role of this protein in brain function. The constitutive and conditional knockout lines reported here will be useful tools for further functional analyses of Kiaa0319.

Anti-inflammatory drug mefenamic acid completely reversed memory loss and brain inflammation in mice genetically engineered to develop symptoms of Alzheimer’s disease and amyloid beta-induced memory loss, a team led by David Brough, PhD, from the University of Manchester has discovered.

The non-steroidal anti-inflammatory drug (NSAID) drug targets an important inflammatory pathway called the NLRP3 inflammasome, which damages brain cells, according to Brough. This is the first time a drug has been shown to target this inflammatory pathway, highlighting its importance in the disease model, Brough said.

Continue reading “Anti-inflammatory drug reverses memory loss in Alzheimer’s-disease-model mice” »

By Kevin Kang

A recent article in ScienceDaily reviews a new approach in Synthetic Biology that allows cells to respond to a series of input stimuli and simultaneously remember the order of these stimuli over many generations. As noted by the senior investigator, Timothy Lu from MIT, combining computation with memory creates complex cellular circuits that can perform logic functions and store memories of events by encoding them in their DNA (1,2). In their current work, Dr. Lu and his colleagues created cells that can remember and respond to three different inputs, including chemical signals in a particular order, and in the future may be able to incorporate even more inputs (1,2,3). The cellular machines thus created are referred to as biological “state machines” because they exist in different states depending on the identity and order of inputs that they receive. The state machines rely on enzymes called recombinases. When activated by a specific input, recombinases either delete or invert a particular segment of DNA depending on the orientation of two DNA target sequences known as recognition sites. The segment of DNA between these sites may have recognition sites for other recombinases that respond to different inputs. Flipping or deleting these sites permanently changes what will happen if a second or third recombinase is later activated. Therefore, a cell’s history is determined by sequencing its DNA. In a version of this system with just two inputs, there are five possible states for this circuit: states corresponding to no input, input A alone, input B alone, A followed by B, and B followed by A. Dr. Lu’s team in MIT has designed and built circuits that record up to three inputs, in which sixteen states are possible (1,2).

Besides creating circuits that record events in a cell’s life and then transmit these memories to future generations, the researchers from MIT also placed genes into the array of recombinase binding sites along with genetic regulatory elements. In these circuits, when recombinases rearrange the DNA, the circuits record the information as well as control which genes get turned on and off. Lu’s lab tested this work in bacteria by color coding the identity and order of input stimuli, so input A followed by B would would lead to bacteria fluorescing red and green, but input B followed by A would lead to red and blue fluorescence. Hence, these techniques can be used not only to record the states that the cells experience over time, but also to deploy in state-dependent gene expression programs (1,2).

Continue reading “Novel Approach to Biological Circuit Design Allows Scientists to Track Cell Lineages” »

They discovered genetically engineered bacteria’s response to shocks.

Genetically engineered E coli bacteria responds to electric shocks by producing a fluorescent protein that can be used as a light source. A team of undergraduate scientists at Newcastle University have created a lightbulb made up of living matter.

Like any other electric bulb, the living light glows to illuminate a room, but is made by replacing some of the traditional electric components in a lightbulb circuit with biological parts.

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Designer babies, the end of diseases, genetically modified humans that never age. Outrageous things that used to be science fiction are suddenly becoming reality. The only thing we know for sure is that things will change irreversibly.

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Continue reading “Genetic Engineering Will Change Everything Forever – CRISPR” »

Leiden theoretical physicists have proven that DNA mechanics, in addition to genetic information in DNA, determines who we are. Helmut Schiessel and his group simulated many DNA sequences and found a correlation between mechanical cues and the way DNA is folded. They have published their results in PLoS One.

When James Watson and Francis Crick identified the structure of DNA molecules in 1953, they revealed that DNA information determines who we are. The sequence of the letters G, A, T and C in the famous double helix determines what proteins are made ny our cells. If you have brown eyes, for example, this is because a series of letters in your DNA encodes for proteins that build brown eyes. Each cell contains the exact same letter sequence, and yet every organ behaves differently. How is this possible?

Researchers have used CRISPR—a revolutionary new genetic engineering technique—to convert cells isolated from mouse connective tissue directly into neuronal cells.

In 2006, Shinya Yamanaka, a professor at the Institute for Frontier Medical Sciences at Kyoto University at the time, discovered how to revert adult connective tissue cells, called fibroblasts, back into immature stem cells that could differentiate into any cell type. These so-called induced pluripotent stem cells won Yamanaka the Nobel Prize in medicine just six years later for their promise in research and medicine.

Since then, researchers have discovered other ways to convert cells between different types. This is mostly done by introducing many extra copies of “master switch” genes that produce proteins that turn on entire genetic networks responsible for producing a particular cell type.

Abstract: Normally, individual molecules of genetic material repel each other. However, when space is limited DNA molecules must be packed together more tightly. This case arises in sperm, cell nuclei and the protein shells of viruses. An international team of physicists has now succeeded in artificially recreating this so-called DNA condensation on a biochip.

Recreating important biological processes in cells to better understand them currently is a major topic of research. Now, physicists at TU Munich and the Weizmann Institute in Rehovot have for the first time managed to carry out controlled, so-called DNA condensation on a biochip. This process comes into play whenever DNA molecules are closely packed into tight spaces, for example in circumstances that limit the available volume.

This situation arises in cell nuclei and in the protein shells of viruses, as well as in the heads of sperm cells. The phenomenon is also interesting from a physical perspective because it represents a phase transition, of sorts. DNA double helices, which normally repel each other because of their negative charges, are then packed together tightly. “In this condensed state they take on a nearly crystalline structure,” says co-author and TU professor Friedrich Simmel.

Controlling the minds of others from a distance has long been a favourite science fiction theme – but recent advances in genetics and neuroscience suggest that we might soon have that power for real. Just over a decade ago, the bioengineer Karl Deisseroth and his colleagues at Stanford University published their paper on the optical control of the brain – now known as optogenetics – in which the firing pattern of neurons is controlled by light. To create the system, they retrofitted neurons in mouse brains with genes for a biomolecule called channelrhodopsin, found in algae. Channelrhodopsin uses energy from light to open pathways so that charged ions can flow into cells. The charged ions can alter the electrical activity of neurons, influencing the animal’s behaviour along the way.

Soon researchers were using implants to guide light to channelrhodopsin in specific neurons in the brains of those mice, eliciting behaviour on demand. At the University of California the team of Anatol Kreitzer worked with Deisseroth to disrupt movement, mimicking Parkinson’s disease and even restoring normal movement in a Parkinsonian mouse. Deisseroth and his colleague Luis de Lecea later demonstrated that it was possible to wake up mice by activating a group of neurons in the brain that control arousal and sleep.

But optogenetics has been challenging. Since light does not easily penetrate dense fatty brain tissue, researchers must implant a fibre-optic cable to bring light into the brain. This limitation led to the development of another, less intrusive technique known as DREADD (designer receptors exclusively activated by designer drugs). In this case, a receptor normally activated by the neurotransmitter acetylcholine is modified to respond to a designer drug not normally found in the body. When the designer drug is delivered, neurons can be manipulated and behaviour changed over a number of hours. The major drawback here: the slow course of drug administration compared with the rapid changes in brain activity that occur during most tasks.

Continue reading “Remote control of the brain is coming: how will we use it?” »