A Panoply of Protozoan Persuasions

Sometimes, it can seem as if men and women are completely different species (at least, that’s what the trashy magazines and multitude of shitty books on relationships would have you believe). Indeed, the behavioral and hormonal differences between the two can often feel like an insurmountable gap for some.

But imagine how much tougher those whinging tits would have it if they had to contend with seven sexes, not just two.

Sound crazy? Well, it’s not crazy if you’re a protozoa. Namely, not if you are Tetrahymena thermophila, which are fairly common fresh water ciliates who just so happen to have seven different genders (conveniently named I – VII). Not only that, but our little unicellular friend also has two nuclei: a macronucleus for all its basic cellular functions, and a micronucleus dedicated to getting it on.

That’s right- their sex life is too complicated for their regular nucleus. An individual sex cannot reproduce with another of the same type (Type I can’t have little protist babies with another Type I, for example), but those 7 sexes can combined in 21 different combinations.

So yeah, it’s a little more complicated than man + woman = baby.

But what’s really interesting about these little guys is that those 7 sexes are not evenly distributed through the population. See, their sex is not determined solely by genetics (like a human’s is). Instead, their genes give them a probability of being born a certain sex- the environment is actually the determining factor (this is not a unique trait- there are many other species, including the three-lined skink lizard, that incorporate temperature and environment into sexual determination).

The sex-influencing mat gene and 13 other alleles are the influencing genetic bits. And the mat gene comes in multiple varieties, so when you really think about it, it’s no wonder the little guys need a completely separate nucleus to handle procreation.

Anyway, the alleles that allow for the possibility of multiple different gender outcomes perform better than those that only allow for one, which eventually skews the population a bit.

Seven sexes may seem like overkill, but it appears to be working for these little guys. They’re like a tiny, Earth-based version of Star Trek Species 8472 (which had 5 sexes, I believe)… only not as ugly:

I’m not sure how you determine this thing’s sex, but sure, go over there and check between its legs… I fucking dare you.

Genetic BeeBoot

Imagine, my galleons, that you could squinch up your eyes and BAM! rewrite your genetic code. A quick change here, a little alteration there, and when you open your eyes again, you’re… different.

Turns out, if you’re a bee, you can do something very similar.

See, when worker honeybees blink their little bee eyes and take their first little bee breaths and start their little bee lives in the world, they start them as nurses. Nurse bees take care of the queen and her young, feeding them and tending to them, like little bee handmaids. Give those little nurses a few weeks, however, and most of them will start switching over to a forager role.

But nursing and foraging are two very different skill sets for the little beelings, and switching between the two roles requires the bees to switch huge swathes of genes on/off (up to 150 genes, in fact). Which is, of course, fascinating. And so, scientists decided to study the crap out of that.

The scientists at Johns Hopkins University School of Medicine in Baltimore let their little worker bees do their nursing job, waiting for them to switch over to foragers. Once the change to forager had been made, the scientists emptied the hive of all the nurses. When the foragers returned to the hive to find their queen and her laravae unattended, many switched back to nurses. During this the whole process, the scientists scanned the DNA of the little bee brains.

What they found was evidence of epigenetic modification, which is a nifty way to essentially flip genetic switches by either placing or removing methyl tags. Methylation doesn’t actually alter the underlying genome, it just allows large chunks of genes to be switched on or off. And the process is entirely reversible.

So, when the bees originally switched from nurse to forager, little methyl tags were popped on a bunch of their genes, switching their function from the nurse duties to the forager tasks. But when the hive needed nurses, the methyl tags were removed, and the bees swapped back to their nursing duties. Brain rebooted and crisis averted.

This is the first evidence of an epigenetic modification being directly linked to a reversible behavior. And why is this so interesting? Why, it turns out many disorders (from addiction to obesity to aging to bipolar disorder) have an epigenetic component. The more we know about how this process works, the closer we get to potentially figuring out how to reverse these disorders.

Pretty cunning, don’t you think?

Are You My Mummy? (See, It’s Funny Because This Post is About a Mummified Child… Get It? GET IT?!)

Some people get drunk and sleep with strangers. I get drunk and read about diseased dead things.

…I love me.

Anyway, an Israeli-South Korean scientific team recently discovered a 16th century mummified child with rather intact organs, which enabled them to perform a liver biopsy and genetic analysis on the little mummy. The cool thing about this (you know, beyond the fact that they are performing a fucking liver biopsy on a little guy that’s been dead for, oh, 500 years or so) is that, in that genetic analysis, the team discovered enough DNA sequences to piece together the oldest full viral genome recorded to date- an ancient strain of hepatitis B.

The particular strain of hep B is known as a genotype C2 sequence and is quite common in Southeast Asia. So, our scientists compared this ancient strain to more modern hep B strains. By studying the mutations and changes (due to environmental pressures), the scientists pinpointed the reconstructed strain’s origin at between 3,000 to 100,000 years ago.

That’s one old virus.

Having such an ancient strain of hep B will allow us to study those same mutations and changes, allowing us a deeper look into how viruses evolve. A more thorough understanding of viral adaptation techniques will allow us to better determine how they spread throughout various regions and how they can survive for thousands of years. Knowledge is really power when it comes to battling viruses- the more we know about them, the more opportunities we have to figure out ways to combat and destroy them.

Also… I just can’t get over how fucking cool it is that we were able to extract this kind of genetic information from a 16th century corpse. I know that I am prone to scientific hero worship, but can any of you honestly say that you aren’t just a wee bit geeked over modern genetic research and technology?

Brand New ‘TAG’: Scientists Rewrite Genome

I love making German puns (especially when nestled within a Doctor Horrible reference)…

Anyway, a recent bit of news out of Harvard, Yale, and MIT (yes, we’re playing with the big boys today) is an interesting piece of tech that could revolutionize genetic manipulation.

Galleons, I assume you are all familiar with the find-and-replace function common in word processors. The Massachusetts Bay Transportation Authority is all too familiar with it, as they recently made a hilarious mistake on their commuter rail tickets in the month of June. Apparently, they did a find-and-replace on their tickets, replacing “MAY” with “JUN”, which led to:

Good times.

On the whole, however, find-and-replace works quite well. And scientists have found a way to harness this common function and apply the basic concept to changing pieces of a cell’s genome.

Skeptical? You aren’t the only ones.

“We did get some skepticism from biologists early on,” says Peter Carr, senior research staff at MIT’s Lincoln Laboratory. “When you’re making so many intentional changes to the genome, you might think something’s got to go wrong with that.”

However, the researchers have managed to do hundreds of targeted edits of E. coli gene stuffs in living cells, with the altered bacteria behaving normally.

So, how do they do it?

There are four nucleotides involved in the genetic code of most DNA (and you’ll probably recognize, if not their names, then the letters themselves): Adenine, Thymine, Guanine, and Cytosine. When you take three of these nucleotides and put them together in sequence, you get a codon. There are 64 unique codons in the genetic code. On the most basic level, most codons add an amino acid to a growing polypeptide chain, which eventually becomes a protein in the capable hands of our friends, ribosomes. However, some codons (known oh-so-cleverly as stop codons) stop the addition of an amino acid to that chain.

Within E. coli, the TAG stop codon in the rarest (like Mew). Which makes it a prime target for our find-and-replace endeavor. An endeavor that requires some much more specialized tech than your average word processor. After all, it’s not like we can just open up a text file and type in our terms, replacing all with the click of a button:

The first bit of tech is multiplex automated genome engineering (MAGE), which locates specific DNA sequences and replaces them with a new sequence as the cell copies its DNA. Using this, scientists assume direct control of the changes happening within a cell.

The second is conjugative assembly genome engineering (CAGE), which gives them precise control over a process that bacteria use to exchange genetic material, wherein one bacterium builds a little extension/bridge to its neighbor and passes a piece of its genetic material to its new bridgemate.

Specifically, scientists used MAGE to manufacture 32 strains of E. coli in which they replaced 10 of the TAG stop codons with TAA stop codons. But there are 314 total edits required to completely replace all of the TAG codons, so scientists decided to use CAGE to make things a bit simpler.

Basically, they built a playoff bracket for their little bacteria strains, with each one sharing a bit of genetic goodness with one other strain. So, after Round 1 of CAGE, 16 strains were standing, each now containing 20 edits. Then they were put back into CAGE for Round 2, which yielded 8 strains with 40 edits each.

They’ve managed to get their strains down to 4 (with 80 edits in each, roughly a quarter of the total 314 needed), and they believe they’re on track to create that single strain with all of the needed substitutions.

After they’ve managed to substitute all of the TAG codons, they are going to go in and delete the machinery that reads that particular codon. After all, if it doesn’t exist anymore, why should the cell be able to read it? That will free up this slot for a whole new purpose, which scientists can use to encode new amino acids.

***

But… why? That’s always the question, galleons. While it just sounds cool to muck around in a cell’s genome like that, we all know scientists have to have some ulterior motives when bothering to create such sophisticated technology in an attempt to fine-tune this kind of genetic tampering.

And this is where shit gets scary.

See, with this technology, scientists could engineer bacteria that are resistant to viruses. Because viruses can only infect a cell if the bacterial and viral genetic codes are the same. Change the genetic code and the bacteria suddenly becomes safe from those pesky viruses.

While scientists claim they could also create little genetic firewalls that prevent their engineered bacteria from spreading their genes to natural bacteria (or just prevent them from being able to survive in the wild in general), I’m just saying…

It sounds like we’ve taken our first steps toward the accidental creation of a zombie virus and the subsequent apocalypse.

Galleons, get your shotguns.

Don’t Wake Me, I Plan On Sleeping In

Behold the wreckage
of night, one heck
of a mess: covers…
cast off in vast
deserts of insomnia
where trepidations bomb
tranquility to rubble. ~Stephen Cushman

The cure for insomnia? Get plenty of sleep. ~W.C. Fields

Potentially good news in the realm of sleep studies, dear galleons, particularly if you (like me) suffer from chronic insomnia:

Scientists have located a “sleep switch” in fruit flies.

A group at Washington University School of Medicine in St. Louis discovered a group of a mere 20 cells in the brains of fruit flies that control when and how long the flies sleep. These 20 cells were found in a part of the fly brain known as the dorsal fan-shaped body:

Paul Shaw, associate professor of neurobiology, led the group as they genetically modified these cells, increasing their activity. This modification led to the flies sleeping an additional seven hours a day. Tweaking this, the group added a gene that made the cells active only at certain temperatures- allowing them to control when/how long the flies slept just by adjusting the temperature in the flies’ environment.

“This is exciting because this induced sleep state so far appears to be very similar to spontaneous sleep,” said Shaw. “That means we can manipulate these cells to explore a whole new realm of questions about the purposes of sleep. Such studies might one day lead us to more natural ways of inducing sleep in humans.”

More on this in a minute.

I suppose you are all wondering the same thing…

Why fruit flies?

Well, a few years ago, a group out of the University of Missouri-Kansas City found that the circadian rhythms of fruit flies are regulated by similar cellular machinery to that of humans. As such, they have become some of the most viable animals models for sleep research.

Strange but true.

Now, while some of the machinery of sleep have strong correlates between flies and humans, fly brains and human brains have very different overall structures. We have yet to find a human counterpart to the dorsal fan-shaped body, but Shaw’s team is looking  to match human brain cell types to the fly brain cells they singled out based on the chemical messengers the cells produce.

So, fellow insomniacs, while this isn’t a quick-fix cure, if Shaw’s group can locate a similar set of cells in the human brain, we might finally have a solution to our sleep problems.

Wouldn’t that be nice?

***

There’s actually more to Shaw’s research than just hope for insomniacs. An even more interesting bit of information to come out of this study revolves around sleep and memory.

For many years, scientists have believed there is a deep connection between sleep and long-term memory formation. Students are frequently made aware of studies that have found studying and then sleeping the night before an exam proves more beneficial than pulling an all-nighter to cram. This has been attributed to the help sleep seems to give to memory formation- by “sleeping on the information,” the brain is actually able to synthesize and store more of it.

Except… while there have been plenty of studies hinting at and dancing around the idea of sleep contributing to memory formation, there’s been surprisingly little real proof of it (there was a pretty solid study in 2009 out of MIT using mice, but if there’s one thing we know about science it’s that a single study does not a theory prove).

Which is why the second part of this study is so important- it directly proves this link.

The reason the memory portion of the study cropped up was as a test of whether the induced sleep was the same as spontaneous sleep. If the induced sleep also proved essential to the formation of long-term memories, the two types of sleep could be considered the same.

To do this, male flies were exposed to other males genetically modified to make female sex pheromones in a process known as ‘courtship conditioning.’

“The subject fly will initiate courtship because of the female pheromones, but the modified male making those pheromones inevitably rejects him,” said Jeff Donlea, a postdoctoral research assistant at Oxford University.

Our researchers used a training protocol that creates a memory that normally only lasts a few hours in flies- after being rejected multiple times by the modified males, the fly learns not to make advances when he approaches the modified males at a later time. Again, this memory normally only lasts a few hours. However, when researchers used that ‘sleep switch’ to induce sleep in the flies, the fly managed to form a long-term memory of the experience which lasted for several days.

Worried that this could be attributed to the fact that they had overly excited those cells, our group activated those sleep cells after training but prevented the flies from actually sleeping. The long-term memories were not formed, proving that it was the sleep that proved essential to memory formation.

Simple though it may seem, it’s one of the few times we’ve made this kind of direct, verifiable connection between sleep and memory formation.

In Which Science Discovers How to Churn Out Plenty of Brain Matter to Keep the Forthcoming Zombie Horde Satisfied

Apologies for the lack of substance lately, dear galleons- I promise to get back on a more normal schedule of posting (i.e. more sex and science).

As you are well aware, I have a soft spot for genetics research. Beyond the fact that it is utterly fascinating, I think it can be traced back to a good friend of mine from TASP who wanted to be a geneticist (and awakened my inner genetics geek).

Which doesn’t matter, really. But we are going to be talking about genetics today, so… huzzah?

Over at Lund University in Sweden, a group has successfully created nerve cells from human skin cells. Which isn’t exactly a new development- stem cell researchers have been turning skin cells into pluripotent stem (IPS) cells, which they’ve proceeded to convert to things like nerve cells, for some time. What’s unique about this latest research is that the Swedish group never created IPS cells. Instead, they managed to reprogram a mature skin cell directly into a nerve cell.

Which is all kinds of cool.

Beyond my geek squee (see this and this), there are reasons this is important. First (and probably rather obviously), this cuts out the use of any form of stem cell in the cell reprogramming game. Using mature cells cuts out the ethical dilemmas posed by research using embryonic stem cells. But skipping that stem cell stage may have an additional (less well-known) benefit: it could prevent the risk of tumors forming at the transplant site. Certain stem cells have the annoying habit of continuing to divide and form tumors after transplantation. This has been a major hindrance to stem cell research, one which could vanish with this new method of cell transmutation.

So, how did our researchers go about morphing skin cells into nerve cells? What they actually did was go in and activate a certain gene in connective tissue cells (fibroblasts). Doing this was enough to switch the skin tissue cells over to certain types of nerve cells.

But wait, there’s more!

By activating two more genes within the skin cells, the research team actually managed to change those fibroblasts into brain cells. Specifically dopamine brain cells, the type of cell which dies in Parkinson’s disease. Naturally, that means this process could prove to be instrumental in creating transplantable replacement dopamine cells from a patient’s existing skin cells (it is presumed that specifically designed cells originating from the patient would be better accepted by the body’s immune system than cells from donor tissue). Scientists also expect brain cells created in this manner could be used as disease models in research on various neurodegenerative diseases.

“This is the big idea in the long run. We hope to be able to do a biopsy on a patient, make dopamine cells, for example, and then transplant them as a treatment for Parkinson’s disease,” says Malin Parmar. Parmar is continuing the research, hoping to develop more types of brain cells using this new method.

While we await further study on how these new cells survive and function within the brain, it’s still an incredible breakthrough. The more we learn about the specifics of the genetic code, the more we are able to do with it and the more impressive research like this is going to get.

Of course, the greater the genetic game, the greater the ethical dilemmas. And the greater the risks. I mean, we all know how this goes. It starts out all fine and sciencey, and the next thing you know, this is happening.

If I Was an Enzyme, I’d Be Helicase So I Could Unzip Your Genes

When I was five, I encountered the concept of DNA for the first time.

Yes, I’m talking about Mr. DNA and the dino resurrection description in Jurassic Park.

This is was the first time a Michael Crichton story (scientifically shaky though they may be) influenced my interest in a scientific concept (the second being Timeline and quantum mechanics). Genetics is a fascinating branch of scientific study, one that has seen great achievements in my lifetime, such as the mapping of most of the human genome and the first cloned animals.

Anyway, I was thinking about genetics this morning while playing BioShock. If you’ve played the game, you know that one of the primary types of character enhancements are plasmids that alter your genetics.

As an aside, if you haven’t played BioShock yet, crawl out from under that rock you’re calling a home and play it. A horror FPS set in an underwater dystopia with a swing/big band soundtrack- it’s basically a wet dream in video game form. And you’ll understand why most gamers now fear the phrase “Would you kindly…”

Anyway, as I was gathering ADAM from the Little Sisters and upgrading my genes like a madwoman, I recalled an article I was reading on DNA the other day.

And decided we should have a genetics/DNA day, dear galleons.

***

Researchers at the University College of Dublin recently sequenced the first Irish genome.

What’s so special about the Irish?

Let’s backtrack for a second here and pay a visit to Charles Darwin’s expedition aboard the HMS Beagle. Darwin landed at the Galápagos Islands and started exploring the native wildlife. Do you remember what he found?

The Galápagos Islands are home to many endemic species (species are are unique to a particular geographic location, such as an island). The very fact that these species had genetic differences from island to island (such as differing shapes of tortoise shells and differences in mockingbirds) helped solidify Darwin’s theory of natural selection, proving animals evolutionarily adapted to their specific environments.

In a closed environment (such as an island), natural selection can lead to striking differences between a mainland species and its island counterpart. The restricted nature of the island’s ecosystem causes genetic variations not seen in other parts of the world.

Enter the Irish.

Ireland is an outlying European island, so it has the geographic potential to be a semi-closed ecosystem, allowing for genetic variations among its inhabitants. Including the Irish people.

It was this possibility that lead Brendan Loftus, head of the Dublin researchers on this project, to sequence the Irish genome in hopes of finding some of these genetic differences.

In this goal, they were successful. The unnamed Irishman (determined to be genotypically repre sentative of Ireland) was found to possess 400,000 novel mutations of single DNA bases. Of these, about 8000 appear to be inherited along with genes known to influence disorders such as inflammatory bowel disease and liver disease.

The Irish have genetic variations dealing with liver disease?

Say it isn’t so.

In all seriousness, these finds are pretty exciting. The newly discovered mutations may help shed light on the genetic basis of these conditions.

***

And now we’ll hop back across the pond to New York City, where Ned Seeman (worst. surname. ever.) of NYU and his team have designed a four-legged, three-armed DNA nanobot spider.

Now, don’t get too excited. As with most scientific advances, these nanobots are far less sophisticated than those you’ve seen on your favorite science fiction program:

Scientists have been creating rudimentary molecular robots for over a decade. Their current aim is to get DNA molecules to organize themselves and move around. No batteries, no information stored in their little bodies. Just movement generated by the power of DNA-DNA interactions.

This is easier said than done.

The latest DNA nanobots can take up to 50 steps all by themselves (a marked achievement in this field) or pick up and transport nanoparticles. But they aren’t going to be doing anything miraculous for quite some time. Right now, these little bots are like drunken toddlers, stumbling and feeling their ways around the manufactured DNA landscape.

That’s right- in order to get these little buggers to move, scientists have to manipulate DNA. Ordinarily, DNA exists as that famous double-stranded helix, stable and unreactive, untwisting only to replicate itself.

But scientists have found ways to work with DNA.

“We’re pushing the envelope of what’s possible with DNA as a working material because we can understand, control and direct DNA more than any other material,” said chemist Lloyd Smith.

One way of manipulating DNA was invented in 2006 by a Caltech biologist named Paul Rothemund. He folded single strands of DNA to make complex two-dimensional shapes (triangles and stars, for example), then designed smaller staple strands that matched up with adjacent DNA folds. These staple strands latched onto the DNA folds and held the little shapes in place. And when you mix these single-stranded pieces together in a solution, the shapes began to assemble themselves.

This is the birth of the DNA origami surface, a key ingredient in the movement equation for our bots. This origami surface becomes a large, two-dimensional “walking track” for the nanobots, a surface scientists can actually program instructions for the spider’s movement into.

Within the origami surface, scientists can elongate key staple strands to form a crawling trail for the bot. These strands stick up from the 2-D origami floor like seaweed. The staple strands’ DNA letter sequences match up with the sequences on the DNA legs of the bot (A with T, C with G), allowing the spider’s legs to “stick” to the staple strands.

That’s not the tricky part, actually. The hardest part of this is getting the bots to pick up their little legs and step to the next strand.

One way to do this is to use the DNA enzymes in the spider’s legs to slice through the staple strand after connecting. This uproots the leg, allowing it to move to a nearby, intact strand.

The obvious problem with this method is that the origami track is used up after only one run.

“If your motors are forever destroying the tracks, you’ve got to rebuild the tracks, which would cost you a huge amount of energy,” said British physicist Andrew Turberfield. “An automobile that chewed up the road behind it would be a bit unpopular.”

So Turberfield is working on a non-destructive method of moving the bots along the origami track. He and his team have come up with a bot that walks along by flipping over itself, essentially somersaulting along the origami track. This method is based on kinesin, a natural molecular motor that carries cargo around the cell.

But, back to Seeman’s bots. See, these little spiders can do more than walk- they can actually pick up and transport cargo with DNA arms. The cargo is gold nanoparticles wrapped in a single strand of DNA. Just like the staple strands are compatible to the spider’s legs, the gold particle’s DNA wrapper is compatible to the spider’s arms. The bot can now either keep its cargo or drop it off at another station along the origami track. By picking up and dropping off various combinations of particles, the spiders can build molecules.

In the future, Seeman hopes to make longer “assembly lines” for the bots. He also hopes to tweak his bots so that they can pick up and transport more than three building blocks. Because the bots bring together molecules one at a time, the bots could piece together molecular puzzles that don’t react well together in nature, which would be a huge boon to chemists.

On the whole, many scientists are excited about the possibilities these nanobots present for the future. As the technology surrounding these molecular bots evolves, scientists hope to see the bots become sophisticated vehicles that can sense their environment and target diseased tissue without harming healthy cells. This would be dizzyingly useful in the field of medicine, not the least of which would be the incredible power these bots would have for fighting diseases such as cancer.

The bots also have the potential to eventually build nanosized computer chips. But this is all far in the future. As Caltech’s Niles Pierce said, “…to take that [nanobot] locomotion and put it to productive use for fabrication of nanoscale components, that’s still a futuristic goal.”

So, while we won’t be seeing any of the good Doctor’s nanogenes any time soon, we are taking a step along the path. Which is pretty much the norm for scientific endeavors. Which is why so many people are disappointed in the reality of scientific research.

But you and I know better than that, galleons. Scientific progress is about taking baby steps along the path toward a greater goal. It’s not all explosions and collisions and bubbling beakers. This is real science. It’s delicate, complex, and much more subtle than in the movies. But in the end, it’s still important.