Taste the Brainbow

Stem cells may secret brain repair substance. What happens when you take a deficient rodent brain and inject it with stem cells? Brain rescue, at least in Alzheimer's-like mice models. This is a more elaborate variation on seminal work from last year.

Rather, the group speculates that the transplanted cells secreted protective neurotrophins, proteins that promote cell survival by keeping neurons from inducing apoptosis (programmed cell death).

What's interesting here is how malleable the system is. The brain is no different than the muscle or the skin in that it can respond to simple biochemical stimuli. Hook and levers, people, hooks and levers.

LaFerla's team genetically engineered mice to lose cells in their hippocampus, a region in the forebrain important for short-term memory formation. These mice were about twice as likely than unaltered rodents to fail a test of their ability to discern whether an object in a cage had been moved since their previous visit.

It would be interesting to see what kind of effect this model would have on the amygdala, the repository of emotional responses and almost always the first target of dementia diseases like Alzheimer's. However, I suppose it is difficult to tell if a mouse if more or less sad than the day before, and they aren't too forthright with that information.

The next step is to isolate this neurotrophin and throw it into a series of in vitro models, see what kinds of things pop up. A little combinatorial chemistry could begin to define what molecular appendage is the business end.

The chances of succumbing to a dementia like Alzheimer's has risen from about 1 in 6 to over 1 in 5 with our slowly creeping increase in life expectancy. With a tsunami of Baby Boomers turning 60, a sense of urgency is likely going to flock towards work of this nature very soon.

There have been a number of research papers touting a connection between certain women's attraction to male sweat, but there appears to be better genetic validation over this phenomenon. As it turns out, there just might be some women out there who find the musky rancor from overclocking men to smell like a breezy spring day. There's a joke in there somewhere, but I'll let you go fish out your favorite instead.

Bom-bom-bom BOM BOM-BOM-BOM-BOMMMMMMMMM

Firefly Science - Luciferase and high throughput screening

Ah, fireflies - or 'Thunderbugs', as I idiomatically referred to them as a child. They are a staple of Summertime nostalgia, and a gateway insect for children to be drawn into the wonderful world of life science. A creature that can eat and create its own light source is something so alien and wonderful to us we are still exploring the science behind it. That said, Luciferase, the principle enzyme responsible for that soft yellow-green glow is a workhorse chemical tool in the high volume screening of compound libraries.

In screening, we often are looking for the activation of genes; that is to say whether the DNA is being transcribed into proteins, where those proteins then go out and perform the various functions of the cell ranging from the germane like cytoskeleton structure to the complex such as the release of a hormone or neurotransmitter. Every time a transcription event occurs, and we can exploit that mechanism for discovery research.

Originally, doing this required the use of radioactive tags - we could label a carbon in a designated molecule that could then be detected as a flash of light. Of course, radioactive work, despite its reliable and reproducible advantages, is not the prime choice of most research labs today.

A gene of interest can be appended downstream with the luciferase DNA and a gene promoter. Doing so allows us to infer that when our gene of interest is activated, our luciferase gene will be activated as well, and the cell will begin to produce luciferase in a ratiometric quantity, dependent on the strength of the promoter.



Now we can assess the amount of our gene of interest by lysing the cell, and adding the substrate luciferin. When this happens, the above reaction can take place, and a product of that reaction is light, which can be detected in the lab by a camera or photomultiplier tube (PMT). The more luciferase present, the more light the lysate will give off to be detected, and from that differential, we can begin to compare different treatments and draw conclusions from those results.

New sources of luciferase are being developed all the time. There's the firefly but there's a lot of different creatures out there with their own ways of giving off light. Mushrooms, sea-pansies and good ol' jellyfish that give us the standby Green Fluorescent Protein (GFP) With a series of enzymes that give off light at different wavelengths, one can create a very involved screen with multiple targets.