The Caffeinator (He'll be back real quick)

We at the Ripsaw enjoy a strong, punch-in-the-face type cup of coffee in the morning, be it Sumatran, Ethiopian or plain or Starbucksy Arabica Breakfast Blend. Indeed, caffeine is often hailed by yours truly as a brain enhancer, a focus accelerant and an all around answer to life in the early hours of the day.=New research, however, shows there is a darker side to caffeine, and it's not all French Roast.


Caffeine mucks with insulin in diabetes.

Caffeine increases risk of miscarriage.

I think there's a unifier here. Caffeine works its magic by keeping a molecule known as cAMP from degrading. With lots of cAMP around, the brain can continue functioning when it would typically trigger fatigue and sleepiness as cAMP levels dropped. Keep the supply fresh and you can go much longer, so to speak.

Here's the thing: cAMP is a nigh-universal metabolic messenger, and is involved in both the metabolism of food as well as complex parts of the reproductive pathways. If you keep cAMP high through caffeine dosing, you're unbalancing something in the body, and in the case of diabetics or pregnant women, there's a much bigger risk involved.

Not that this should keep you from your favorite caffeinated beverage of choice, but perhaps coffee isn't the panacea wunderdrug we'd all like it to be.

Indecision clouds my vision

Certain genes might lead to suicidal tendencies. Insert rock lyric here.

This is a nice story to point to because it illustrates the active scientific process. An early finding seems to be on stable ground, so the next step is to see if that finding can be supported or corroborated by expanded testing in multiple platforms. This is both the beauty and strength of the discipline.

For this study, Laje and colleagues analyzed DNA samples from 1,915 participants, looking for associations between reports of suicidal ideation at 768 sites in 68 genes.

Statistically, I like the methodology. It's remarkable to note this kind of study probably could not have taken place five years ago, at least in this capacity, the technology is so new.

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.

Torcetrapib: Down in Flames

As you might have heard, Pfizer yanked torcetrapib out of the pipeline this weekend, just two days after the brass had hailed the new lipitor/torcetrapib hybrid as the crown jewel of the new product profile. The ramifications are unsettling to say the least. With Lipitor set to come off patent next year, there's a huge gaping hole in Pfizer's portfolio and there appear to be few projects with the legs to fill the gap in the short term. Feel free to look over the technical details.This comes on the heels of Pfizer announcing a large cut to its sales force, as well as as-yet-unannounced cuts across the entire company in January. I have a feeling it's going to be an atrocious new year for my pals over in the Ann Arbor campus