Lean, green protein-making machines

When researchers become enamored of a particular protein and want to study it, one of the first things they do is figure out how to get their hands on a LOT of it. That way, they can put it in test tubes, add and subtract different chemicals and alter the conditions and environment (temperature, pH, etc.) to figure out what really makes the protein act the way it does.

It may seem reasonable to suggest that these researchers just go collect the protein from its natural source. After all, the organism that produces the protein must be pretty good at it, right?

Ok, so if a researcher is studying a human protein, they can come after you with a needle for regular plasma draws or have you pee in a cup and filter out the protein from your fluids… but what happens if they are studying a protein that you pretty much suck at making, that is made in a few different varieties depending on whether or not you’re healthy or sick, that isn’t found in your blood or urine? Would you want researchers to come after you to extract, for instance, GREB1, which is found in prostatic tissue and prostate cancer? Probably not…

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But there is good news for you and your prostate: scientists have been making proteins in the lab for a long time! (Time out: if you need a little DNA/protein tutorial, go on back to my DNA 101 post). So what is the recipe for a protein?

1.     Take the DNA sequence that codes your protein and put it into an organism that won’t care if you’re all up in its prostrate

2.     Turn that organism into a protein factory, letting it churn out millions of copies of your protein

3.     Isolate—filter—your protein out of all the other gunk

4.     Viola! You now have gobs of your favorite protein to use to your heart’s content

Ok, so of course some of these steps are a little more complicated than just waving a magic science wand. In fact, I hear a stampede of grad students (my younger self included) at my door, ready to skewer me for compacting years of blood, sweat, and tears into a few flippant bullet points. 

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 But the important technological advance here is to hijack a biological system in order to do your heavy lifting.

What are the types of critters scientists use as their workhorses? Usually bacteria and yeast; sometimes insect, plant, or mammalian cells that can live in culture. The key property is that these cells grow quickly and robustly and merrily make protein, even protein that it wouldn’t normally make from the extra gene that you put into it.

And that, my dears, is how you make perfect protein every time! (how do you type a Julia Child voice?) apronstrings.com

So, if this technology has been around for a long time and is the part of the Materials and Methods section in a scientific paper that gets glossed over (unless you’re one of those grad students trying to do the same thing), why am I going on and on about it?

Because a research group out of the University of California, San Diego, has figured out how to use algae—that green gunk that covers ponds and lakes and smells funny—to make a malaria protein.

Honestly, this in and of itself isn’t something I’d normally find inspiration in to write about, other than the fact that I love keeping up on malaria research.

The reason I found this study so interesting is the fact that in all my various E-mail subscriptions and Twitter feeds and Facebook updates, I kept reading about it! Sure, the fact that they used algae is kind of cool, but scientists are always trying to find the best organism to use to get the most protein they can. So why was it everywhere?

Marketing! That’s how! This study is a perfect case study of knowing how to make your story sexy. I don’t know if these researchers have a publicist or what, but seriously, it’s brilliant: use the algae to produce a protein that could potentially be a MALARIA VACCINE TARGET, and suddenly you’ve got an angle. Now, instead of a headline (that would never be written because it’s boring) reading “Researchers Add Another Organism to a Long List of Things That Can Make Protein in the Lab,” they get ones like “Biologists Produce Potential Malarial Vaccine from Algae." Much better.

I don’t want to trivialize the importance of this study, nor do I want to make it sound like they’re undeserving of the press. I personally think this is really freaking cool, based on the fact that I did my thesis project on malaria and on the fact that it’s a prime example of how scientists can make their work accessible to the general public. They do not say they have cured the disease or found a vaccine; instead, they have given their finding potential context and a reason for people to care.

And giving people a reason to care and instilling in them passion is, in my opinion, where science communication often falls flat.

So, kudos to Stephan Mayfield and his team for their success and for being an example of how you can do good science, do science well, and write about both for your fellow scientists and for the general public.

Oo-ooh, that smell.

Growing up in a region of the States where mosquitoes grew to monstrous proportions, forcing us to sweat around the campfire in skin-encasing pants and long-sleeved shirts, worrying if we’d all spontaneously combust due to the cloud of DEET forming a force-field around us, I think I’ve heard all derivations of methods to keep mosquitoes away and why they’re attracted to people – some more than others. For me and for most of us living in industrialized countries, finding ways to repel mosquitoes is mostly just about nuisance. We want to avoid those irritating itchy bumps and sleepless nights from that one damn mosquito that got trapped in the bedroom with us. However, for hundreds of millions of people living in sub-Saharan Africa, South America, and Southeast Asia, repelling mosquitoes is really a life-or-death battle.

The reason we in the States and other industrialized nations don’t have to worry about anything more than a mosquito bite (and the occasional West Nile virus scare) is because the mosquito species (Anopheles gambiae, for the Latin-proficient) that transmits the most fatal malaria parasite (another tongue-twister: Plasmodium falciparum) was successfully eradicated from these regions. In third-world countries, the mosquitoes still wreak havoc on the population. Of course, the hot and humid climate is perfect for these little pests. But the problem is much bigger: these are poor, undeveloped nations without the infrastructure or financial resources to implement large-scale eradication procedures. There have been great successes with insecticide-treated bed nets, but obviously a lot more work needs to be done, since 1-3 million people still die from malaria every year, making it one of the top three infectious disease killers (the other two being HIV-AIDS and tuberculosis).

Fortunately, scientists are on the case to figure out what attracts mosquitoes to humans. Even better, they know something more than what we grew up hearing: “you’re just not sweet enough,” or “just stop breathing and they won’t bother you.” Actually, mosquitoes have special odorant receptors in their neurons that let them “smell” different chemicals. That’s right, even though mosquitoes don’t have noses, they can smell! There are many different types of these odorant receptors that allow the mosquitoes to detect different chemicals – very similar to how humans can detect different odors (Su C et al. Cell 2009;139(1):45-59). A fascinating article was just published in the journal Nature, in which the authors wanted to know exactly which receptors were responsible for detecting human odors – no, not the odors you and I can detect on a crowded subway, but the chemicals we emit just by being human (Carey AF, et al. Nature 2010;464:66-71). The researchers did something really tricky: they knew the gene for each individual receptor. They also had mutant fruit flies that were missing their odorant receptors. The scientists could insert the mosquito receptor into a fruit fly neuron! Why is this so cool, other than just the simple fact that they could technically do this? Because they could put one receptor into one neuron, without all the other receptors around, and they could tell exactly what each receptor could respond to. In other words, they have a neuron with receptor A, and another with receptor B. They expose these neurons to different chemicals, some of which are found in human odors. If neuron A responds to a chemical, but not neuron B, the scientists would know that receptor A allows the mosquito to recognize this chemical. Some chemicals activated just one receptor, while some chemicals activated several; some receptors were activated by a small range of chemicals, while others by a large range (the researchers called this “tuning”).

These findings are really important to finding new ways to eradicate mosquitoes. If researchers can find receptors that let mosquitoes recognize humans, they can start researching how to block this response. If the mosquito can’t find her next meal, the consequences are pretty obvious. Or, if researchers can figure out the main chemicals being recognized by the mosquitoes, they can design traps to lure the mosquitoes away from human populations. Importantly, these techniques wouldn’t involve giving medicine or treatments to people or interfering with their daily lives.