Tuesday, May 31, 2011

More winemaking magic

A few posts ago, I described the outstanding lecture by Kerith Overstreet of Bruliam Wines on the biochemistry of wine (link). Although I tried to capture the essence of her talk, there is now a recording available including her slides. If you are interested in the topic but kept thinking ‘WTF is this guy talking about’, I recommend you hear it straight from the source. Here is the link to the audio.

Bruliam Wines also has a blog and today’s post (here’s the
link) has a great discussion of how sulfur dioxide is used in wines. Added as potassium metabisulfite, the acidic wine converts it into sulfur dioxide (as well as bisulfite and the conjugate base, sulfite). Each of these reducing agents has a role in protecting or preserving the wine and just like anything else, too much of a good thing is bad. Finding the right balance so that the wine is free of bacteria, protected from oxidation over the long term, but does not lose its color or subtle flavors is yet another example of the magic of winemaking. Enjoy!

What's in YOUR papaya?

Papaya: The fruit with it's
own symposium

Some people out there are concerned over whether the food they are eating has been genetically modified (GM).  We don’t worry much about that in the Lab since there is nothing even remotely genetic about Twinkies or Mountain Dew.  Still, I mentioned before that a hackerspace was a great place to do some food surveillance.  During my research into traditional methods (PCR detection, etc), I ran across an article published a few years ago that described a really simple method to test for GM Papayas.  If you are a big papaya eater, this could be important, but the method could also be more general.

Papaya are susceptible to a nasty virus called Papaya Ringspot Virus (PRSV) which creates havoc in the fields.  Long ago, scientists found that by introducing a gene for the coat protein of this virus into the papaya genome, they could block the virus from attacking the plant.  However, another gene comes along for the ride – namely, a gene used for genetic selection in the lab.  When scientists introduce a gene into a plant cell, they often use a reporter to show them which clones successfully received the gene and which do not.  This marker is an enzyme called beta-glucuronidase (GUS).  What makes this such a good indicator of a GM papaya is that non-transgenic papaya do not have this enzyme, so if you can detect this in your fruit, it has to be transgenic.  One way to this, of course, is to use DNA primers specific for GUS and use PCR to try and amplify the DNA specific for the enzyme.  You could also try to sequence the DNA extracted from the papaya and look for the sequence for GUS (or any other inserted gene, such those for the PRSV coat proteins).  The complete genome of one type of GM papaya (the SunUp variety) was published in 2008 (Nature abstract) and is freely available at GenBank (link).  Others have also been subsequently published.

X-Gluc: A GUS substrate

Fortunately, for papaya lovers, there is an easier way.  5-bromo-4-chloro-3-indoyl glucuronide (X-Gluc) is a substrate for GUS and gets converted to glucuronic acid and a precipitate which happens to be blue.  Therefore, a very easy way to look for the presence of the enzyme is to screen directly with X-Gluc.  You don’t even have to purify DNA!  Simply take the seeds from the fruit of interest and smash them up really well.  Then incubate them in the presence of X-Gluc for about a day and if you see blue, you’ve got a GM papaya!  Here is a link to a recent article that describes the general idea (abstract).  In principle, if your hackerspace has access to X-Gluc, testing for the presence of GM papaya is extremely easy.  Scientists have used this same method to track cross-pollination between GM plants and non-transgenic neighbors.  One example was reported at the International Symposium on Papaya (abstract).  Yes, a papaya conference… and I thought I got a lot of grief for doing phage display.  Anyhow, I’ll have another post or two about this type of food monitoring and pretty soon you’ll be just like the USDA – only without the bureaucracy and bad jokes.

Wednesday, May 25, 2011

Backyard Biotechs: One step up from the hacker

A chemical that catches iron

I’ve had several readers comment to me something along these lines: “Yeah, it would be really cool to discover a drug or something, but Merck isn’t going to develop a drug from a hacker.”  Maybe not, but check out this article from the June issue of The Atlantic describing a couple of California biotechs who are taking the virtual approach to drug development (link).  FerroKin is developing an orally available iron chelator (a chemical that traps and removes iron) as a treatment for iron overload in patients requiring recurrent blood transfusions.  The need for this type of drug is pretty high in this patient population but the overall market size is small.  Big Pharma won’t touch something like this because it wouldn’t be worth it to them.  However, to a small, virtual biotech this represents a significant opportunity.  Synthesizing iron chelators requires some sophisticated chemical equipment but I think it could be done relatively easily in a chemical hackerspace by experienced chemists (I would probably blow up half the lab trying to get the hot water on).  Furthermore, designing these drugs is fairly straightforward as well.  The iron that needs to be bound is in the blood (this makes it WAY easier since the drug doesn’t have to go into cells) and the rules about metal chelation are pretty well understood.  The odds of finding compounds for lead development are quite good.  FerroKin (link) raised some venture capital money to do preclinical and early clinical trials (all outsourced to contract research companies so FerroKin didn’t do any of it on their own) and the results so far appear promising.

I could definitely see this happening more frequently.  The process might even be similar to trying to publish a young adult novel about some biopunks.  Something gets tested at a hackerspace and looks promising.  After the intellectual property rights are secured, the inventor shops it around to ‘agents’ who are actively looking for scientific projects of that type.  Agents sign the investor and then pitch the package to virtual biotechs for possible development.  It won’t be easy at all as the bar will be very high, but a similar process is happening right now at Big Pharma (except that the projects are coming from academic labs and not amateur scientists).  I look forward to the day when all the starving writers trying to write The Next Great Novel will be fighting for sofa space at the coffee shop with the starving drug hunters trying to design The Next Big Drug.

Sunday, May 22, 2011

Snail shells that amplify bioluminescence

Hinea brasiliana - courtesy of The Scripps Institution of Oceanography
Remember when I discussed various genetic monstrosities (cue maniacal laughter) in my last post?  Here is one we don’t even have to create because Mother Nature has done a pretty remarkable job already (She is the ORIGINAL biopunk!).  Check out this link that describes some research out of the Scripps Institution of Oceanography (link).  In an article published last December (see below) they describe a unique bioluminescent snail (Hinea brasiliana) found off of Australia.  The fact that this thing glows is somewhat unusual, but how it achieves the effect is quite cool.  When the snail encounters something dangerous (a predator, a diver’s foot, a sinking ship, etc) it activates a luminous display on its body in an effort to scare the threat away.  To do this, the light must be activated in such a way that it is emitted from the shell (ie, be visible to the predator).  What is remarkable is that even though the shell is opaque and colored, only the wavelength of light from the bioluminescent signal is selectively diffused.  Even more amazing is that the shell acts as an amplifier, so that the snail appears larger than it really is! 

Obviously, trying to understand the properties of the shell and how this material specifically diffuses and amplifies the bioluminescence has broad implications in commercial development of better optical materials (fiber-optics, perhaps?).  But, can you imagine engineering these properties into the leaves or bark of a tree?  Or into specific areas on your wall or ceiling?  Soft, energy efficient lighting with little or no pollution.  Understanding and replicating this phenomenon seems like a ripe area for garage scientists.  How about a science fair project looking at the transmission of light through this (and other) shells as a function of wavelength?  Is the shell acting like a filter? A lens?  What is the chemical and structural composition of the shell? Do small pores allow the selective diffusion of light? Does the light transmit backwards through the shell?  Do related species of snails transmit different wavelengths of light?  Is the light really amplified or is it just an illusion?  Maybe it’s time to pop into the Dark Lab and answer some of these questions…

Deheyn D. and Wilson N., Bioluminescent signals spatially amplified by wavelength-specific diffusion through the shell of a marine snail. Proceedings of the Royal Society B (Biological Sciences), Dec 15 2010.

Friday, May 20, 2011

Be a Martian tourist!!

Wanna really get away?  Go to Mars!  You could use a commercial, deep-space rocket and travel for months in cramped quarters with a bunch of other tourists.  (Imagine getting on a plane for a 4000 hour, non-stop flight with all those screaming kids… better be lots of free booze on that flight!)  Or, you could take your touristy pictures from the comfort of home!  Check out the High Resolution Imaging Science Experiment (HiRISE).  It’s run out of the University of Arizona in conjunction with NASA and is focused on using high resolution images of Mars to study the weather, geology, topology, tectonics, and climate change.  Scientists have been using this data for years to develop models for these processes but Mars is a pretty big planet and the number of interesting sites to study is pretty vast.  I mean, we haven’t finished exploring Earth yet!  So, there is an opportunity for us Dark Lab types to dig into this treasure trove of data.  Much like the fuzzy blob site (blobs post), you can sift through pictures and highlight interesting or unusual features.  But they also take it one step further… with HiWish (link) you can actually suggest (using a Google-Mars like platform) Martian features to be photographed.  If selected, the Mars Reconnaissance Orbiter will be sent commands to zoom in on your target and take high resolution images.  Amazingly cool!  Many of the gallery pictures are really cool.  The image above is a shot of a very recent (like, within the last year) meteorite strike.  Other examples of interesting features would be odd canyons, rock formations, and that little green man with the Death Blaster.  Apparently, Martians don’t like being peeped at with telescopes.

Thursday, May 19, 2011

Hack-shacks, biopunks, and the next revolution

Imagine this is 1976 (try to block out the bell-bottoms and disco music), and I wrote a blog about a couple of pimple-faced teens who had built this swell micro-computer in their garage.  They put the thing in a box and bring it to a local do-it-yourself computing club where a bunch of other computer junkies say things like “that’s totally rad, man”.  Yup, they’re computer hackers and two guys like this went on to start Apple Computer.  For all of us, life was never the same again.  Now fast-forward 35 years. 

The iPhone's great-great-grandad

The DIY biotechnology (ie, biohacking) movement has been growing for a few years but is still very much in its infancy. I remember going to a local community college with my dad and seeing him load the punched card machine to get a computer the size of a room do a routine calculation.  I could probably do that on my cell phone now.  The concept of a world wide web with a blogging program that could transmit my drivel around the world instantly was so far beyond what was possible at that time.  We are currently in the “computers as big as a room” phase with biohacking.  Doing projects is cumbersome.  Some ideas are still beyond the scope of current technology.  But it will not be long before the biological equivalent of the PC will be developed and it will rock the world.
Will biopunks cure cancer? Unlikely. But the discovery of new genetic targets for attacking cancer or infectious diseases is a good niche for garage drug hunters.  Most of the protein engineering work I do could be done at home with free software on the web, so the theoretical design of biologic drugs is also likely within reach.  Another likely application is the development of diagnostic kits.  With the big push into personalized medicine, I see huge opportunities there.  A biohacker can search the literature for biomarkers for a particular disease, or even try to find them on their own.  A few proof-of-concept experiments done in a well-equipped hack-shack (more on these in a future post) and you could have a prototype diagnostic kit.  Would you spend a couple hundred bucks for a toaster-sized cube that monitors the detailed health profile of your family?  I would.  Exposure to a cold virus? You know it on Day 1. Infection brewing?  You know about it before it even gets sore, plus you also know what type of infection you have and the resistance profile.  Want to make sure you’re your food is all-natural and pathogen-free?  No problem.  Monitor metabolic pathways for signs of imbalance (very early indicators of a number of diseases)?  We need to learn more about these pathways, but in principle this is also very possible.  A primitive version of this type of device could probably be made today.

The OpenPCR machine: The great-great grandad of ????

How about less practical gadgets like the iPod?  Designer plants?  Plants with leaves that glow in the dark?  Well within reach.  Carrots that taste like cotton candy? Probably doable.  How about genetic genealogy?  How fun would it be to try and find DNA samples from long-lost relatives (hair strands?) and map genetic contributions from them.  Kids might even be into collecting genes.  Pick up a leaf or a feather or a dead bug and process the DNA.  Compare genes, find rare and unusual enzymes, make trading cards.  It could be bigger than Pokemon!  Ok, maybe not, but still, somebody out there is going develop these things and the next Apple Computer is going to be born.  Check out the OpenPCR that is being developed by a couple of early biohackers (link)… could this be Apple 1?
Someday I’ll be drinking a glass of cab and telling my granddaughter that back in the old days, I had a whole group of scientists with a lab full of expensive equipment trying to identify and target genes. And it took years. Blah, blah, blah… and she’ll wander off and play with the genetically engineered mouse she made from a kit under the soft light of a bioluminescent tree.

Tuesday, May 10, 2011

Reverse Engineering of Neolithic Wines (or The Coolest Job in the World!)

Chateau Jiahu: A blast from the past
 I do protein engineering for a major pharmaceutical company and I love my job.  I get to work on interesting scientific questions, use the coolest technology ever, and at the end of it all, contribute to developing medicines that might help people.  What’s not to love?  Then, sometimes, I get job-envy.  That happened last week when I read about Patrick McGovern.  He leads the Biomolecular Archaeology lab at the U. Penn. Museum of Archaeology and Anthropology (link) and if he ever wants to trade jobs for a day, I’m game. (Unless it’s Wednesday, because that’s the day we get free food.) He’s been called “the Indiana Jones of ancient ales, wines and extreme beverages”.  Yeah, apparently they had Jager-bombs back then. This guy’s research involves chemistry, genetics, archeology, anthropology, and wine/beer making.  Sometimes wine was also used for healing, and he also tries to determine the pharmacological significance of these chemicals, such as their antibacterial or anti-cancer properties (but I’ll save that for another post).

Malvidin: A wine fossil?

How does he do all this?  Vessels are dug out of archaeological sites around the world (Egypt, Iran, etc) and although they are empty, there is still residue on the sides, like grape juice stains.  These residues have specific chemical signatures that can be detected (usually by mass spectrometry) even after thousands of years. Remember the magic stuff I talked about in the winemaking post (link)?  The presence of these compounds provides strong evidence for fermentation.  However, most of these exist in very small quantities, making them difficult to detect in ancient residue.  The most abundant chemicals in wine (such as tartaric acid) are present in grapes and are not necessarily a marker for fermentation (a jar of wine would look the same as a jar of grape juice).  However, a recent study (abstract) has demonstrated that malvidin or syringic acid may be better markers for evidence of grape fermentation. Malvidin is the chemical that gives red wine its color, but more importantly, it is one of those magic chemicals that polymerizes over time.  In the lab, malvidin polymers can be broken into syringic acid (which is easy to detect) and large amounts of syringic acid can suggest the pot once held fermented wine.  The identification of other compounds or even the sequencing of ancient grape DNA can provide further evidence of wine or beer production.

Although this information provides important clues for studying the rise and fall of ancient civilizations, there is another, much more interesting consequence: Reverse engineering. By identifying the components and byproducts of ancient wines and beer, it becomes possible to try and reproduce today what was made thousands of years ago. McGovern has worked with Dogfish Head Brewery to make modern versions of ancient ales. One example is Chateau Jiahu (link), a fermented beverage of rice, honey and fruit that was made based on the chemical residue found in pottery jars from a Neolithic village known as Jiahu. Chateau Jiahu is an exciting opportunity to taste a drink that has been extinct for over 9000 years! Archeology, biochemistry, and beer… yeah, that’s a cool job.

Sunday, May 1, 2011

Find the bubbles and fuzzy red blobs

Wow~ bubbles, green knots, red blobs

I mentioned in an earlier post that it had never been a better time to participate in exciting research projects.  Unfortunately, this no longer involves injections of semi-purified plant extracts in an effort ‘to see what happens’.  Today, you can participate in important research efforts in the comfort (and safety!) of your own home.  The common term for this is ‘citizen science’, which is a (dorky) term I hate.  The research doesn’t have to be dorky.  NASA Science News just highlighted one such effort called The Milky Way Project (link) where volunteers can contribute to the analysis of deep sky pictures obtained by the Spitzer space telescope.  After a free sign up, you view images taken by this instrument (many of them never before seen by a human) and identify interesting features in the picture.  One particular project is looking for ‘bubbles’ in interstellar gas.  A simple tutorial explains how to identify and mark the images, which are then submitted for further analysis.  What is so great about this is that anybody can do it!  I’ve ‘bubbled’ quite a few of these images and I can tell you, some of them are truly breath-taking.  The process reminds me of those gem mining attractions in the mountains of North Carolina (I’m sure they’re everywhere).  You get a bag of dirt and sift through it in a slough.  Most bags contain a number of small emeralds or rubies, but every once in awhile you find a honker.  That’s the scientific term for a big-ass emerald.  These images are much the same.  Some are pretty dull, some have a number of interesting features, and every so often you find a honker.  All of these ‘bubbled’ pictures are then fed back through the image analysis software with the ultimate goal of figuring out what the bubbles are, how they are formed, what purpose they serve in star formation. 

Two UFRBs (unidentified fuzzy red blobs)
Bubbles are boring?  You also learn to identify green knots of gas, which are unknown objects that scientists are very interested in learning more about.  These are a fairly new discovery as are the so-called ‘fuzzy red objects’,  which is the technical term for ‘WTF is that red blob’.  Somewhere there are happy graduate students who no longer have to stare at these images 24/7 until they start drawing bubbles in the freckle patterns of their significant others.  What’s in it for you?  Aside from the opportunity to contribute to research on the cutting edge of astronomy, there is also a chance to discover something totally new.  Something unknown to mankind.  Something which may contribute to a major breakthrough in the origin of the universe.  New data comes in from these instruments on a regular basis, so get off Facebook, pull up a chair next to your favorite astrophysicist and stare into the unknown.  I find that a good cabernet goes well with the fuzzy red blobs.