We started with a welcome and gratitude to the organizers and attendees and our tagline “Science, I am Just That Into You.” We were selected to appear with a lot of fantastic programming over the weekend.
We introduced our 3 panelists:
Adrienne Roehrich, your panel moderator and the chemistry editor at Double X Science
All 3 have PhDs in their respective fields – Emily is a developmental biologist, Ray is an analytical chemist, and Adrienne is a physical chemist. Emily and Ray are prolific writers. You can find their articles all over the internet and in print. Ray is a staff member for GeekGirlCon and Adrienne is a Special Agent volunteer. All 3 are active on social media and welcome live-tweeting and suggest the #DXS hashtag along with the #GGC12. And you can use the @DoubleXSci for the panel.
Then a poll of the room to see who had heard of the site. Only a few attendees were already familiar with the site, so we told them that DoubleXScience covers a lot of current science. For example on (the previous) Monday, Emily posted about the Mars Curiosity Rover touchdown. In July, the physics editor covered the Higgs particle announcement. We also cover timeless, yet updated science, such as pregnancy and other health issues that we editors perceive to be of interest to ourselves and our readers.
It’s hard to discuss what Double X Science is without discussing who it is.
After a review of who all the people on that particular slide are and what they have to do with Double X Science, three questions were asked by the moderator:
In November of 2011, Emily founded Double X Science, Emily what was your motivation in founding the site and what was then and is now your vision for it?
As mentioned, we have content from editors, other sites and contributors. Ray was the first contributor to the site – what attracted you to Double X Science?
What do the attendees want to know?
And then our discussion really got started. Thankfully, we had 3 great tweeters attending, so I can just point you along their tweets:
[&amp;amp;amp;amp;amp;amp;lt;a href="http://storify.com/fiainros/double-x-science-panel-at-geekgirlcon-2012" target="_blank"&amp;amp;amp;amp;amp;amp;gt;View the story "Double X Science panel at GeekGirlCon 2012" on Storify&amp;amp;amp;amp;amp;amp;lt;/a&amp;amp;amp;amp;amp;amp;gt;]
Photo by Adrienne Roehrich and used with permission.
[Ed. note: I (Emily) just attended the National Association of Science Writers annual conference in Raleigh, NC, where I moderated a session on managing the information deluge that can overwhelm those of us who deeply engage in social media. During the session, Tinker Ready noted the all-woman makeup of our panel and asked about the role of social media in helping women in science. She also asked me a few questions after the session. Below is a repost of the resulting piece, which first appeared at Nature's SpotOn Website. SpotOn focuses on how science is communicated and carried out online, something that obviously interests our Double X Science team a great deal. We repost here with permission, and our thanks to the SpotOn folks.]
The tweet read “What makes this panel rare at science conf? #sciwri12deluge”. The attached photos featured four women leading a session at this weekend’s National Association of Science Writers meeting.
Emily Willingham Credit: Tinker Ready
Moderator and science writer Emily Willingham said she and Scientific American blog editor, Bora Zivkovic, planned it that way when they were putting together a Twitter session for the Raleigh, North Carolina meeting.
“We just thought —how often do you get to see that?” Willingham said, with a nod to the panel. “I go to a lot of scientific conferences and you don’t see this that much.”
The topic of the session was how to manage Twitter. But, the panel’s subtext was: women have a prominent place in scientific social networks. And, said Willingham and others, social networks have a role in promoting women in science.
“What you see on Twitter is a kind of de-gendering, in a positive way, of what people have to say,” she said. “You present more with words on Twitter than with anything else. Words and personality are important. “
Panel member Marie-Claire Shanahan, a science communication professor at the University of Alberta, agreed.
“I don’t pay that much attention on Twitter to whether anyone is male or female,” she said “They are often just a Twitter handle.” Gender “is so much not part of the first impression on Twitter.”
Nor is anything below the neck. “Unfortunately,” Willingham said “…That’s useful.”’
“You see people whose heads you recognize and you think, ‘wow, I had no idea what their bodies looks like’,” she said. “By that time, you’ve already fixed who they are in terms of their personality and what you think of them.
Twitter and other social networks also offer a way for women scientists to connect. It allows women who work at home to stay plugged in. Willingham home schools two of her children. She also manages the Double X Science site, which promises to bring “evidence-based science writing to women.”
“In between, I’m watching Twitter go by,” she said. “I work at home, but in this way, I’m connected to humanity. I’m connected to my colleagues, I’m connected to the conversations that are going on about sciences.”
– Tinker Ready
The opinions expressed in this post do not necessarily agree or conflict with those of the DXS editorial team and contributors.
The four basic categories of molecules for building life are carbohydrates, lipids, proteins, and nucleic acids.
Carbohydrates serve many purposes, from energy to structure to chemical communication, as monomers or polymers.
Lipids, which are hydrophobic, also have different purposes, including energy storage, structure, and signaling.
Proteins, made of amino acids in up to four structural levels, are involved in just about every process of life.
The nucleic acids DNA and RNA consist of four nucleotide building blocks, and each has different purposes.
The longer version
Life is so diverse and unwieldy, it may surprise you to learn that we can break it down into four basic categories of molecules. Possibly even more implausible is the fact that two of these categories of large molecules themselves break down into a surprisingly small number of building blocks. The proteins that make up all of the living things on this planet and ensure their appropriate structure and smooth function consist of only 20 different kinds of building blocks. Nucleic acids, specifically DNA, are even more basic: only four different kinds of molecules provide the materials to build the countless different genetic codes that translate into all the different walking, swimming, crawling, oozing, and/or photosynthesizing organisms that populate the third rock from the Sun.
Big Molecules with Small Building Blocks
The functional groups, assembled into building blocks on backbones of carbon atoms, can be bonded together to yield large molecules that we classify into four basic categories. These molecules, in many different permutations, are the basis for the diversity that we see among living things. They can consist of thousands of atoms, but only a handful of different kinds of atoms form them. It’s like building apartment buildings using a small selection of different materials: bricks, mortar, iron, glass, and wood. Arranged in different ways, these few materials can yield a huge variety of structures.
We encountered functional groups and the SPHONC in Chapter 3. These components form the four categories of molecules of life. These Big Four biological molecules are carbohydrates, lipids, proteins, and nucleic acids. They can have many roles, from giving an organism structure to being involved in one of the millions of processes of living. Let’s meet each category individually and discover the basic roles of each in the structure and function of life.
You have met carbohydrates before, whether you know it or not. We refer to them casually as “sugars,” molecules made of carbon, hydrogen, and oxygen. A sugar molecule has a carbon backbone, usually five or six carbons in the ones we’ll discuss here, but it can be as few as three. Sugar molecules can link together in pairs or in chains or branching “trees,” either for structure or energy storage.
When you look on a nutrition label, you’ll see reference to “sugars.” That term includes carbohydrates that provide energy, which we get from breaking the chemical bonds in a sugar called glucose. The “sugars” on a nutrition label also include those that give structure to a plant, which we call fiber. Both are important nutrients for people.
Sugars serve many purposes. They give crunch to the cell walls of a plant or the exoskeleton of a beetle and chemical energy to the marathon runner. When attached to other molecules, like proteins or fats, they aid in communication between cells. But before we get any further into their uses, let’s talk structure.
The sugars we encounter most in basic biology have their five or six carbons linked together in a ring. There’s no need to dive deep into organic chemistry, but there are a couple of essential things to know to interpret the standard representations of these molecules.
Check out the sugars depicted in the figure. The top-left molecule, glucose, has six carbons, which have been numbered. The sugar to its right is the same glucose, with all but one “C” removed. The other five carbons are still there but are inferred using the conventions of organic chemistry: Anywhere there is a corner, there’s a carbon unless otherwise indicated. It might be a good exercise for you to add in a “C” over each corner so that you gain a good understanding of this convention. You should end up adding in five carbon symbols; the sixth is already given because that is conventionally included when it occurs outside of the ring.
On the left is a glucose with all of its carbons indicated. They’re also numbered, which is important to understand now for information that comes later. On the right is the same molecule, glucose, without the carbons indicated (except for the sixth one). Wherever there is a corner, there is a carbon, unless otherwise indicated (as with the oxygen). On the bottom left is ribose, the sugar found in RNA. The sugar on the bottom right is deoxyribose. Note that at carbon 2 (*), the ribose and deoxyribose differ by a single oxygen.
The lower left sugar in the figure is a ribose. In this depiction, the carbons, except the one outside of the ring, have not been drawn in, and they are not numbered. This is the standard way sugars are presented in texts. Can you tell how many carbons there are in this sugar? Count the corners and don’t forget the one that’s already indicated!
If you said “five,” you are right. Ribose is a pentose (pent = five) and happens to be the sugar present in ribonucleic acid, or RNA. Think to yourself what the sugar might be in deoxyribonucleic acid, or DNA. If you thought, deoxyribose, you’d be right.
The fourth sugar given in the figure is a deoxyribose. In organic chemistry, it’s not enough to know that corners indicate carbons. Each carbon also has a specific number, which becomes important in discussions of nucleic acids. Luckily, we get to keep our carbon counting pretty simple in basic biology. To count carbons, you start with the carbon to the right of the non-carbon corner of the molecule. The deoxyribose or ribose always looks to me like a little cupcake with a cherry on top. The “cherry” is an oxygen. To the right of that oxygen, we start counting carbons, so that corner to the right of the “cherry” is the first carbon. Now, keep counting. Here’s a little test: What is hanging down from carbon 2 of the deoxyribose?
If you said a hydrogen (H), you are right! Now, compare the deoxyribose to the ribose. Do you see the difference in what hangs off of the carbon 2 of each sugar? You’ll see that the carbon 2 of ribose has an –OH, rather than an H. The reason the deoxyribose is called that is because the O on the second carbon of the ribose has been removed, leaving a “deoxyed” ribose. This tiny distinction between the sugars used in DNA and RNA is significant enough in biology that we use it to distinguish the two nucleic acids.
In fact, these subtle differences in sugars mean big differences for many biological molecules. Below, you’ll find a couple of ways that apparently small changes in a sugar molecule can mean big changes in what it does. These little changes make the difference between a delicious sugar cookie and the crunchy exoskeleton of a dung beetle.
Sugar and Fuel
A marathon runner keeps fuel on hand in the form of “carbs,” or sugars. These fuels provide the marathoner’s straining body with the energy it needs to keep the muscles pumping. When we take in sugar like this, it often comes in the form of glucose molecules attached together in a polymer called starch. We are especially equipped to start breaking off individual glucose molecules the minute we start chewing on a starch.
Double X Extra: A monomer is a building block (mono = one) and a polymer is a chain of monomers. With a few dozen monomers or building blocks, we get millions of different polymers. That may sound nutty until you think of the infinity of values that can be built using only the numbers 0 through 9 as building blocks or the intricate programming that is done using only a binary code of zeros and ones in different combinations.
Our bodies then can rapidly take the single molecules, or monomers, into cells and crack open the chemical bonds to transform the energy for use. The bonds of a sugar are packed with chemical energy that we capture to build a different kind of energy-containing molecule that our muscles access easily. Most species rely on this process of capturing energy from sugars and transforming it for specific purposes.
Polysaccharides: Fuel and Form
Plants use the Sun’s energy to make their own glucose, and starch is actually a plant’s way of storing up that sugar. Potatoes, for example, are quite good at packing away tons of glucose molecules and are known to dieticians as a “starchy” vegetable. The glucose molecules in starch are packed fairly closely together. A string of sugar molecules bonded together through dehydration synthesis, as they are in starch, is a polymer called a polysaccharide (poly = many; saccharide = sugar). When the monomers of the polysaccharide are released, as when our bodies break them up, the reaction that releases them is called hydrolysis.
Double X Extra: The specific reaction that hooks one monomer to another in a covalent bond is called dehydration synthesis because in making the bond–synthesizing the larger molecule–a molecule of water is removed (dehydration). The reverse is hydrolysis (hydro = water; lysis = breaking), which breaks the covalent bond by the addition of a molecule of water.
Although plants make their own glucose and animals acquire it by eating the plants, animals can also package away the glucose they eat for later use. Animals, including humans, store glucose in a polysaccharide called glycogen, which is more branched than starch. In us, we build this energy reserve primarily in the liver and access it when our glucose levels drop.
Whether starch or glycogen, the glucose molecules that are stored are bonded together so that all of the molecules are oriented the same way. If you view the sixth carbon of the glucose to be a “carbon flag,” you’ll see in the figure that all of the glucose molecules in starch are oriented with their carbon flags on the upper left.
The orientation of monomers of glucose in polysaccharides can make a big difference in the use of the polymer. The glucoses in the molecule on the top are all oriented “up” and form starch. The glucoses in the molecule on the bottom alternate orientation to form cellulose, which is quite different in its function from starch.
Storing up sugars for fuel and using them as fuel isn’t the end of the uses of sugar. In fact, sugars serve as structural molecules in a huge variety of organisms, including fungi, bacteria, plants, and insects.
The primary structural role of a sugar is as a component of the cell wall, giving the organism support against gravity. In plants, the familiar old glucose molecule serves as one building block of the plant cell wall, but with a catch: The molecules are oriented in an alternating up-down fashion. The resulting structural sugar is called cellulose.
That simple difference in orientation means the difference between a polysaccharide as fuel for us and a polysaccharide as structure. Insects take it step further with the polysaccharide that makes up their exoskeleton, or outer shell. Once again, the building block is glucose, arranged as it is in cellulose, in an alternating conformation. But in insects, each glucose has a little extra added on, a chemical group called an N-acetyl group. This addition of a single functional group alters the use of cellulose and turns it into a structural molecule that gives bugs that special crunchy sound when you accidentally…ahem…step on them.
These variations on the simple theme of a basic carbon-ring-as-building-block occur again and again in biological systems. In addition to serving roles in structure and as fuel, sugars also play a role in function. The attachment of subtly different sugar molecules to a protein or a lipid is one way cells communicate chemically with one another in refined, regulated interactions. It’s as though the cells talk with each other using a specialized, sugar-based vocabulary. Typically, cells display these sugary messages to the outside world, making them available to other cells that can recognize the molecular language.
Lipids: The Fatty Trifecta
Starch makes for good, accessible fuel, something that we immediately attack chemically and break up for quick energy. But fats are energy that we are supposed to bank away for a good long time and break out in times of deprivation. Like sugars, fats serve several purposes, including as a dense source of energy and as a universal structural component of cell membranes everywhere.
Fats: the Good, the Bad, the Neutral
Turn again to a nutrition label, and you’ll see a few references to fats, also known as lipids. (Fats are slightly less confusing that sugars in that they have only two names.) The label may break down fats into categories, including trans fats, saturated fats, unsaturated fats, and cholesterol. You may have learned that trans fats are “bad” and that there is good cholesterol and bad cholesterol, but what does it all mean?
Let’s start with what we mean when we say saturated fat. The question is, saturated with what? There is a specific kind of dietary fat call the triglyceride. As its name implies, it has a structural motif in which something is repeated three times. That something is a chain of carbons and hydrogens, hanging off in triplicate from a head made of glycerol, as the figure shows. Those three carbon-hydrogen chains, or fatty acids, are the “tri” in a triglyceride. Chains like this can be many carbons long.
Double X Extra: We call a fatty acid a fatty acid because it’s got a carboxylic acid attached to a fatty tail. A triglyceride consists of three of these fatty acids attached to a molecule called glycerol. Our dietary fat primarily consists of these triglycerides.
Triglycerides come in several forms. You may recall that carbon can form several different kinds of bonds, including single bonds, as with hydrogen, and double bonds, as with itself. A chain of carbon and hydrogens can have every single available carbon bond taken by a hydrogen in single covalent bond. This scenario of hydrogen saturation yields a saturated fat. The fat is saturated to its fullest with every covalent bond taken by hydrogens single bonded to the carbons.
Saturated fats have predictable characteristics. They lie flat easily and stick to each other, meaning that at room temperature, they form a dense solid. You will realize this if you find a little bit of fat on you to pinch. Does it feel pretty solid? That’s because animal fat is saturated fat. The fat on a steak is also solid at room temperature, and in fact, it takes a pretty high heat to loosen it up enough to become liquid. Animals are not the only organisms that produce saturated fat–avocados and coconuts also are known for their saturated fat content.
The top graphic above depicts a triglyceride with the glycerol, acid, and three hydrocarbon tails. The tails of this saturated fat, with every possible hydrogen space occupied, lie comparatively flat on one another, and this kind of fat is solid at room temperature. The fat on the bottom, however, is unsaturated, with bends or kinks wherever two carbons have double bonded, booting a couple of hydrogens and making this fat unsaturated, or lacking some hydrogens. Because of the space between the bumps, this fat is probably not solid at room temperature, but liquid.
You can probably now guess what an unsaturated fat is–one that has one or more hydrogens missing. Instead of single bonding with hydrogens at every available space, two or more carbons in an unsaturated fat chain will form a double bond with carbon, leaving no space for a hydrogen. Because some carbons in the chain share two pairs of electrons, they physically draw closer to one another than they do in a single bond. This tighter bonding result in a “kink” in the fatty acid chain.
In a fat with these kinks, the three fatty acids don’t lie as densely packed with each other as they do in a saturated fat. The kinks leave spaces between them. Thus, unsaturated fats are less dense than saturated fats and often will be liquid at room temperature. A good example of a liquid unsaturated fat at room temperature is canola oil.
A few decades ago, food scientists discovered that unsaturated fats could be resaturated or hydrogenated to behave more like saturated fats and have a longer shelf life. The process of hydrogenation–adding in hydrogens–yields trans fat. This kind of processed fat is now frowned upon and is being removed from many foods because of its associations with adverse health effects. If you check a food label and it lists among the ingredients “partially hydrogenated” oils, that can mean that the food contains trans fat.
Double X Extra: A triglyceride can have up to three different fatty acids attached to it. Canola oil, for example, consists primarily of oleic acid, linoleic acid, and linolenic acid, all of which are unsaturated fatty acids with 18 carbons in their chains.
Why do we take in fat anyway? Fat is a necessary nutrient for everything from our nervous systems to our circulatory health. It also, under appropriate conditions, is an excellent way to store up densely packaged energy for the times when stores are running low. We really can’t live very well without it.
Phospholipids: An Abundant Fat
You may have heard that oil and water don’t mix, and indeed, it is something you can observe for yourself. Drop a pat of butter–pure saturated fat–into a bowl of water and watch it just sit there. Even if you try mixing it with a spoon, it will just sit there. Now, drop a spoon of salt into the water and stir it a bit. The salt seems to vanish. You’ve just illustrated the difference between a water-fearing (hydrophobic) and a water-loving (hydrophilic) substance.
Generally speaking, compounds that have an unequal sharing of electrons (like ions or anything with a covalent bond between oxygen and hydrogen or nitrogen and hydrogen) will be hydrophilic. The reason is that a charge or an unequal electron sharing gives the molecule polarity that allows it to interact with water through hydrogen bonds. A fat, however, consists largely of hydrogen and carbon in those long chains. Carbon and hydrogen have roughly equivalent electronegativities, and their electron-sharing relationship is relatively nonpolar. Fat, lacking in polarity, doesn’t interact with water. As the butter demonstrated, it just sits there.
There is one exception to that little maxim about fat and water, and that exception is the phospholipid. This lipid has a special structure that makes it just right for the job it does: forming the membranes of cells. A phospholipid consists of a polar phosphate head–P and O don’t share equally–and a couple of nonpolar hydrocarbon tails, as the figure shows. If you look at the figure, you’ll see that one of the two tails has a little kick in it, thanks to a double bond between the two carbons there.
Phospholipids form a double layer and are the major structural components of cell membranes. Their bend, or kick, in one of the hydrocarbon tails helps ensure fluidity of the cell membrane. The molecules are bipolar, with hydrophilic heads for interacting with the internal and external watery environments of the cell and hydrophobic tails that help cell membranes behave as general security guards.
The kick and the bipolar (hydrophobic and hydrophilic) nature of the phospholipid make it the perfect molecule for building a cell membrane. A cell needs a watery outside to survive. It also needs a watery inside to survive. Thus, it must face the inside and outside worlds with something that interacts well with water. But it also must protect itself against unwanted intruders, providing a barrier that keeps unwanted things out and keeps necessary molecules in.
Phospholipids achieve it all. They assemble into a double layer around a cell but orient to allow interaction with the watery external and internal environments. On the layer facing the inside of the cell, the phospholipids orient their polar, hydrophilic heads to the watery inner environment and their tails away from it. On the layer to the outside of the cell, they do the same.
As the figure shows, the result is a double layer of phospholipids with each layer facing a polar, hydrophilic head to the watery environments. The tails of each layer face one another. They form a hydrophobic, fatty moat around a cell that serves as a general gatekeeper, much in the way that your skin does for you. Charged particles cannot simply slip across this fatty moat because they can’t interact with it. And to keep the fat fluid, one tail of each phospholipid has that little kick, giving the cell membrane a fluid, liquidy flow and keeping it from being solid and unforgiving at temperatures in which cells thrive.
Steroids: Here to Pump You Up?
Our final molecule in the lipid fatty trifecta is cholesterol. As you may have heard, there are a few different kinds of cholesterol, some of which we consider to be “good” and some of which is “bad.” The good cholesterol, high-density lipoprotein, or HDL, in part helps us out because it removes the bad cholesterol, low-density lipoprotein or LDL, from our blood. The presence of LDL is associated with inflammation of the lining of the blood vessels, which can lead to a variety of health problems.
But cholesterol has some other reasons for existing. One of its roles is in the maintenance of cell membrane fluidity. Cholesterol is inserted throughout the lipid bilayer and serves as a block to the fatty tails that might otherwise stick together and become a bit too solid.
Cholesterol’s other starring role as a lipid is as the starting molecule for a class of hormones we called steroids or steroid hormones. With a few snips here and additions there, cholesterol can be changed into the steroid hormones progesterone, testosterone, or estrogen. These molecules look quite similar, but they play very different roles in organisms. Testosterone, for example, generally masculinizes vertebrates (animals with backbones), while progesterone and estrogen play a role in regulating the ovulatory cycle.
Double X Extra: A hormone is a blood-borne signaling molecule. It can be lipid based, like testosterone, or short protein, like insulin.
As you progress through learning biology, one thing will become more and more clear: Most cells function primarily as protein factories. It may surprise you to learn that proteins, which we often talk about in terms of food intake, are the fundamental molecule of many of life’s processes. Enzymes, for example, form a single broad category of proteins, but there are millions of them, each one governing a small step in the molecular pathways that are required for living.
Levels of Structure
Amino acids are the building blocks of proteins. A few amino acids strung together is called a peptide, while many many peptides linked together form a polypeptide. When many amino acids strung together interact with each other to form a properly folded molecule, we call that molecule a protein.
For a string of amino acids to ultimately fold up into an active protein, they must first be assembled in the correct order. The code for their assembly lies in the DNA, but once that code has been read and the amino acid chain built, we call that simple, unfolded chain the primary structure of the protein.
This chain can consist of hundreds of amino acids that interact all along the sequence. Some amino acids are hydrophobic and some are hydrophilic. In this context, like interacts best with like, so the hydrophobic amino acids will interact with one another, and the hydrophilic amino acids will interact together. As these contacts occur along the string of molecules, different conformations will arise in different parts of the chain. We call these different conformations along the amino acid chain the protein’s secondary structure.
Once those interactions have occurred, the protein can fold into its final, or tertiary structure and be ready to serve as an active participant in cellular processes. To achieve the tertiary structure, the amino acid chain’s secondary interactions must usually be ongoing, and the pH, temperature, and salt balance must be just right to facilitate the folding. This tertiary folding takes place through interactions of the secondary structures along the different parts of the amino acid chain.
The final product is a properly folded protein. If we could see it with the naked eye, it might look a lot like a wadded up string of pearls, but that “wadded up” look is misleading. Protein folding is a carefully regulated process that is determined at its core by the amino acids in the chain: their hydrophobicity and hydrophilicity and how they interact together.
In many instances, however, a complete protein consists of more than one amino acid chain, and the complete protein has two or more interacting strings of amino acids. A good example is hemoglobin in red blood cells. Its job is to grab oxygen and deliver it to the body’s tissues. A complete hemoglobin protein consists of four separate amino acid chains all properly folded into their tertiary structures and interacting as a single unit. In cases like this involving two or more interacting amino acid chains, we say that the final protein has a quaternary structure. Some proteins can consist of as many as a dozen interacting chains, behaving as a single protein unit.
A Plethora of Purposes
What does a protein do? Let us count the ways. Really, that’s almost impossible because proteins do just about everything. Some of them tag things. Some of them destroy things. Some of them protect. Some mark cells as “self.” Some serve as structural materials, while others are highways or motors. They aid in communication, they operate as signaling molecules, they transfer molecules and cut them up, they interact with each other in complex, interrelated pathways to build things up and break things down. They regulate genes and package DNA, and they regulate and package each other.
As described above, proteins are the final folded arrangement of a string of amino acids. One way we obtain these building blocks for the millions of proteins our bodies make is through our diet. You may hear about foods that are high in protein or people eating high-protein diets to build muscle. When we take in those proteins, we can break them apart and use the amino acids that make them up to build proteins of our own.
How does a cell know which proteins to make? It has a code for building them, one that is especially guarded in a cellular vault in our cells called the nucleus. This code is deoxyribonucleic acid, or DNA. The cell makes a copy of this code and send it out to specialized structures that read it and build proteins based on what they read. As with any code, a typo–a mutation–can result in a message that doesn’t make as much sense. When the code gets changed, sometimes, the protein that the cell builds using that code will be changed, too.
Biohazard!The names associated with nucleic acids can be confusing because they all start with nucle-. It may seem obvious or easy now, but a brain freeze on a test could mix you up. You need to fix in your mind that the shorter term (10 letters, four syllables), nucleotide, refers to the smaller molecule, the three-part building block. The longer term (12 characters, including the space, and five syllables), nucleic acid, which is inherent in the names DNA and RNA, designates the big, long molecule.
DNA vs. RNA: A Matter of Structure
DNA and its nucleic acid cousin, ribonucleic acid, or RNA, are both made of the same kinds of building blocks. These building blocks are called nucleotides. Each nucleotide consists of three parts: a sugar (ribose for RNA and deoxyribose for DNA), a phosphate, and a nitrogenous base. In DNA, every nucleotide has identical sugars and phosphates, and in RNA, the sugar and phosphate are also the same for every nucleotide.
So what’s different? The nitrogenous bases. DNA has a set of four to use as its coding alphabet. These are the purines, adenine and guanine, and the pyrimidines, thymine and cytosine. The nucleotides are abbreviated by their initial letters as A, G, T, and C. From variations in the arrangement and number of these four molecules, all of the diversity of life arises. Just four different types of the nucleotide building blocks, and we have you, bacteria, wombats, and blue whales.
RNA is also basic at its core, consisting of only four different nucleotides. In fact, it uses three of the same nitrogenous bases as DNA–A, G, and C–but it substitutes a base called uracil (U) where DNA uses thymine. Uracil is a pyrimidine.
DNA vs. RNA: Function Wars
An interesting thing about the nitrogenous bases of the nucleotides is that they pair with each other, using hydrogen bonds, in a predictable way. An adenine will almost always bond with a thymine in DNA or a uracil in RNA, and cytosine and guanine will almost always bond with each other. This pairing capacity allows the cell to use a sequence of DNA and build either a new DNA sequence, using the old one as a template, or build an RNA sequence to make a copy of the DNA.
These two different uses of A-T/U and C-G base pairing serve two different purposes. DNA is copied into DNA usually when a cell is preparing to divide and needs two complete sets of DNA for the new cells. DNA is copied into RNA when the cell needs to send the code out of the vault so proteins can be built. The DNA stays safely where it belongs.
RNA is really a nucleic acid jack-of-all-trades. It not only serves as the copy of the DNA but also is the main component of the two types of cellular workers that read that copy and build proteins from it. At one point in this process, the three types of RNA come together in protein assembly to make sure the job is done right.
Of Heroin, Honorable Mentions, and Hawkeye: A day I will never forget
By Double X Science Biology Editor Jeanne Garbarino “I look forward to seeing you in 3 months when you will be a whole person again.”
Those were my parting words to a special person in my life who was embarking on an undoubtedly difficult journey toward sobriety. It was only 7:45am on Friday, June 1st, but already I had learned that the strings from a bikini top make a good tourniquet, and I actually held the syringe that, only moments before, contained a bolus of heroin. I am still trying to believe that this really was the last time.
As I attempted to wrap my head around what was happening, I remembered a description of a heroin high as told to me by a former addict. According to this person, being on heroin feels like you’ve been swaddled in a warm blanket, and gently rocked by a loving mother, except the loving mother was actually the devil.
Though I could never really understand what it feels like to be hooked on heroin, this helped me make some sense of it. But, as much as I wanted to be sympathetic, I also wanted to grab my friend by the shoulders and scream. “Why have you done this to yourself? Why have you done this to us?” It has truly been a difficult time, watching this person struggle. And finding out that I can’t control any of it was probably the hardest lesson I’ve ever learned.
Still, life must go on.
I took a few deep breaths, which helped to quiet the tremble, and began to gather my thoughts. What was it that I had to do today? As if I flipped some switch, I began to plan out my day – renew my parking permit, finish that Western blot, read that thesis, and get that new post up on the site.
Then, around 8:15am, I received an unexpected phone call. It was Liz Bass from the Center of Communicating Science at Stony Brook University. She was calling to see if I could make Alan Alda’s World Science Festival discussion about the Flame Challenge, which was to occur at 4pm that afternoon. Not really knowing what was in store, I quickly accepted (um, hello, Alan Alda). A second phone call about 20 minutes later informed me that I would be joining Alan on stage. Was this really happening? In about 30 minutes time, I went from despair to elation. I also went to the store to buy a skirt since I was already in transit to my lab (and was dressed like a “scientist”).
As I sat on the train, I began to reflect. Much of my free time during the month of March was dedicated to producing an entry to Alan Alda’s Flame Challenge contest, which, in an effort to raise science communication awareness, asked scientists from all over the world to define a flame to an 11 year old. Because I enjoy working on a team, I asked my fellow scicommies, Deborah Berebichez and Perrin Ireland, to join me on this endeavor (three times the brain power!). For several weeks, we worked on the script, and regularly discussed our progress during late night Google hangouts (which is a fantastic way to collaborate). This was mostly due to the fact that we all have day jobs and obligations outside of work. Luckily for me, Debbie and Perrin were willing to meet at a time that coincided after my children’s bedtime routine.
This experience was truly fun and rewarding. Each of us has a certain set of strengths, which when combined, seemed to just synergize. We literally examined every word in the script to make sure that it was clear, concise, and hopefully captivating. Furthermore, we wanted to make sure that it was something an 11-year-old would both learn from and enjoy.
But, we did labor over one particular issue, and that was our use of the Bohr Model to represent an atom. While this model might be commonplace in many classroom textbooks, scientists now know that electrons exist in orbitals, also known as electron clouds, and the calculations to determine the exact location(s) of an electron are based on probability. Clearly, this was something very different than stating that electrons simply orbit around a nucleus.
The analogy that electrons travel around the nucleus in the same way that planets travel around the sun is downright inaccurate. However, this is an analogy that is still commonly used and is, in my opinion, a great example of how we sacrifice accuracy for simplicity. I believe that this is the greatest challenge for a science communicator.
As we talked through this issue, we tried to not lose site of the actual mission, which was to explain a flame to an 11 year old. Would it help our story to break down the currently accepted atomic theory or would it detract from it? In the end, we decided to keep our atomic structure simple, but noted that it was a simplified version of an atom. We figured that by having this little disclaimer, it would inform our audience that there is more to it that what we showed, and maybe it would lead them down a road of scientific inquiry.
Perhaps it was this attention to detail that landed our Flame Challenge video a spot in the top 15 entries (FYI there were close to 900 entries). Or perhaps it was because our entry was cute and artistic. Whatever the reason, we proudly accepted our honorable mention, and I was looking forward to discussing our video with the man himself.
Getting back to Friday, June 1st. I arrived at the Paley Center for Media around 3:30pm (in a new skirt) and was immediately brought up to the 11th floor and into the green room of Alan Alda. There, I met my fellow awardees (a combination of finalists and honorable mentions), and of course Alan Alda, who was fantastically charming and funny. We all sat, around an old table, on which was a lovely array of cheese, nuts, banana chips, and get this, Swedish fish! I don’t know what it was about the Swedish fish, but seeing this candy helped calm my nerves.
Alan helped us all to break the ice, and discussed his plans for the event. Apparently we would be leading a panel discussion, and I would be on that panel. On a stage. In front of a very large audience. And it was to be webcasted. So I popped a few of those Swedish fish and told myself to not be nervous.
As my jaw worked to chew those sticky sweet candies, I couldn’t help but think about when I was a kid and how I used to sit with my dad and watch M*A*S*H. I never would have believed you if you told me that I was going to be hanging out with Hawkeye when I was older. But, there he was, telling us about the birth of the Flame Challenge. I was tempted to ask him where Corporal Klinger is these days, but decided that my time would be better spent getting the plan for the panel firmed up in my brain.
After some quick chitchat, we were asked to make our way to the auditorium. Seating was charted and mics were checked and around 4pm, it all began. About an hour into it, we were asked to come on stage. Each of our entries were highlighted, followed by a chance speak our piece. Add in some Q&A from the audience and the panel discussion was complete. A hearty round of applause later, I found myself getting whisked away for pictures.
When the dust began to settle, I grabbed a beer and started to decompress. I just couldn’t believe how this day turned out, especially given its start. The stresses my family and I have been dealing with have certainly taken its toll on all of us, and I am grateful for that little dose of Hawkeye to help lighten things up. I’m not sure if I will ever experience a day like that again, but that’s ok with me.
You may have had the experience: A medication you and a friend both take causes terrible side effects in you, but your friend experiences none. (The running joke in our house is, if a drug has a side-effect, we’ve had it.) How does that happen, and why would a drug that’s meant to, say, stabilize insulin levels, produce terrible gastrointestinal side effects, too? A combination of techy-tech scientific approaches might help answer those questions for you — and lead to some solutions.
It’s no secret I love lab technology. I’m a technophile. A geek. I call my web site “Biotechnically Speaking.” So when I saw this paper in the September issue of Nature Biotechnology, well, I just had to write about it.
The paper is entitled, “Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators.” If you read that and your eyes glazed over, don’t worry –- the article is way more interesting than its title.
Those trees on the right are called SPADE trees. They map cellular responses to different stimuli in a collection of human blood cells. Credit: (c) 2012 Nature America [Nat Biotechnol, 30:858--67, 2012]
Here’s the basic idea: The current methods drug developers use to screen potential drug compounds –- typically a blend of high-throughput imaging and biochemical assays – aren’t perfect. If they were, drugs wouldn’t fail late in development. Stanford immunologist Garry Nolan and his team, led by postdoc Bernd Bodenmiller (who now runs his own lab in Zurich), figured part of that problem stems from the fact that most early drug testing is done on immortalized cell lines, rather than “normal” human cells. Furthermore, the tests that are run on those cells aren’t as comprehensive as they could be, meaning potential collateral effects of the compounds might be missed. Nolan wanted to show that flow cytometry, a cell-analysis technique frequently used in immunology labs, can help reduce that failure rate by measuring drug impacts more holistically.
Nolan is a flow cytometry master. As he told me in 2010, he’s been using the technique for more than three decades, and even used a machine now housed in the Smithsonian.
In flow cytometry, researchers treat cells with reagents called antibodies, which are immune system proteins that recognize and bind to specific proteins on cell surfaces. Each type of cell has a unique collection of these proteins, and by studying those collections, it is possible to differentiate and count the different populations.
Suppose researchers wanted to know how many T cells of a specific type were present in a patient’s blood. They might treat those cells with antibodies that recognize a protein known as CD3 to pick those out. By adding additional antibodies, they can then select different T-cell subpopulations, such as CD4-positive helper T cells and CD8-positive cytotoxic T cells, both of which help you mount immune responses.
Cells of the immune system Source: http://stemcells.nih.gov/info/scireport/chapter6.asp
In a basic flow cytometry experiment, each antibody is labeled with a unique fluorescent dye –- the antibody targeting CD3 might be red, say, and the CD4 antibody, green. The cells stream past a laser, one by one. The laser (or lasers –- there can be as many as seven) excites the dye molecules decorating the cell surface, causing them to fluoresce. Detectors capture that light and give a count of how many total cells were measured and the types of cells. The result is a kind of catalog of the cell population. For immune cells, for example, that could be the number of T cells, B cells (which, among other things, help you “remember” previous invaders), and macrophages (the big cells that chomp up invaders and infected cells). By comparing the cellular catalogs that result under different conditions, researchers gain insight into development, disease, and the impact of drugs, among other things.
But here’s the problem: Fluorescent dyes aren’t lasers, producing light of exactly one particular color. They absorb and emit light over a range of colors, called a spectrum. And those spectra can overlap, such that when a researcher thinks she’s counting CD4 T cells, she may actually be counting some macrophages. That overlap leads to all sorts of experimental optimization issues. An exceptionally talented flow cytometrist can assemble panels of perhaps 12 or so dyes, but it might take months to get everything just right.
That’s where the mass cytometry comes in. Commercialized by DVS Sciences, mass cytometry is essentially the love-chid of flow cytometry and mass spectrometry, combining the one-cell-at-a-time analysis of the former with the atomic precision of the latter. Mass spectrometry identifies molecules based on the ratio of their mass to their charge. In DVS’ CyTOF mass cytometer, a flowing stream of cells is analyzed not by shining a laser on them, but by nuking them in superhot plasma. The nuking reduces the cell to its atomic components, which the CyTOF then measures.
Specifically, the CyTOF looks for heavy atoms called lanthanides, elements found in the first of the two bottom rows of the periodic table, like gadolinium, neodymium, and europium. These elements never naturally occur in biological systems and so make useful cellular labels. More to the point, the mass spectrometer is specific enough that these signals basically don’t overlap. The instrument will never confuse gadolinium for neodymium, for instance. Researchers simply tag their antibodies with lanthanides rather than fluorophores, and voila! Instant antibody panel, no (or little) optimization required.
Periodic Table of Cupcakes, with lanthanides in hot pink frosting. Source: http://www.buzzfeed.com/jpmoore/the-periodic-table-of-cupcakes
Now back to the paper. Nolan (who sits on DVS Sciences’ Scientific Advisory Board) and Bodenmiller wanted to see if mass cytometry could provide the sort of high-density, high-throughput cellular profiling that is required for drug development. The team took blood cells from eight donors, treated them with more than two dozen different drugs over a range of concentrations, added a dozen stimuli to which blood cells can be exposed in the body, and essentially asked, for each of the pathways we want to study, in each kind of cell in these patients’ blood, what did the drug do?
To figure that out, they used a panel of 31 lanthanides –- 10 to sort out the cell types they were looking at in each sample, 14 to monitor cellular signaling pathways, and 7 to identify each sample.
I love that last part, about identifying the samples. The numbers in this experiment are kind of staggering: 12 stimuli x 8 doses x 14 cell types x 14 intracellular markers per drug, times 27 drugs, is more than half-a-million pieces of data. To make life easier on themselves, the researchers pooled samples 96 at a time in individual tubes, adding a “barcode” to uniquely identify each one. That barcode (called a “mass-tag cellular barcode,” or MCB) is essentially a 7-bit binary number made of lanthanides rather than ones and zeroes: one sample would have none of the 7 reserved markers (0000000); one sample would have one marker (0000001); another would have another (0000010); and so on. Seven lanthanides produce 128 possible combinations, so it’s no sweat to pool 96. They simply mix those samples in a single tube and let the computer sort everything out later.
This graphic summarizes a boatload of data on cell signaling pathways impacted by different drugs. Credit: (c) 2012 Nature America [Nat Biotechnol, 30:858--67, 2012]
When all was said and done, the team was able to draw some conclusions about drug specificity, person-to-person variation, cell signaling, and more. Basically, and not surprisingly, some of the drugs they looked at are less specific than originally thought -– that is, they affect their intended targets, but other pathways as well. That goes a long way towards explaining side effects. But more to the point, they proved that their approach may be used to drive drug-screening experiments.
There’s an old saying: You can’t be a little bit pregnant. Pregnancy is what you might call a binary condition – you either are with child, or you’re not. Home pregnancy tests embody this thinking. You pee on the end of a stick, and three minutes later you either do or do not see a line in the results window. Congratulations, you’re expecting!
Biologically, of course, things are a bit more complicated. Pregnancy tests check for the presence of a particular protein, human chorionicgonadotropin (hCG), that is also elevated in women with breast and ovarian cancers. As a result, it’s sometimes useful to be able to quantify the levels of hCG – or any other so-called “biomarker” – with a bit more precision. A new diagnostic device, developed by a team of Texas researchers and described in the journal Nature Communications, enables precisely that.
The team developed what’s called a microfluidic device, a circuit of tiny channels etched into glass (or sometimes plastic or a rubber polymer) that enable researchers to run chemical assays on tiny volumes of sample. That’s helpful when the sample is particularly precious or hard to come by – a drop of blood from a newborn baby, say.
Microfluidic devices, sometimes called “lab-on-a-chip” devices (because they resemble computer chips in both design and size), are popular in both drug development companies and research laboratories, as well as in the clinic. Their reduced volumes and size mean they use less reagent volumes (making them relatively inexpensive) and produce less waste. They are also faster and higher throughput than many traditional experiments, and are easily automated.
The downside is in the data output. To read the results of a microfluidic assay, researchers generally need some large and expensive piece of hardware that can, for instance, interrogate the chip with a laser to measure fluorescence intensity. That requirement isn’t a problem for most research labs, but it does reduce the likelihood that the technology can be adopted by your general practitioner. And it makes the development of microfluidics-based home tests, analogous to a home pregnancy kit, all but impossible.(*)
To circumvent these problems, the Texas team used a clever “SlipChip” design. A SlipChip is a microfluidic device formed by overlaying two glass plates, whose channels can form either of two flow paths depending on the position of the top plate relative to the bottom. In one configuration, the channels flow left-to-right; in the other (that is, after sliding or “slipping” the top plate), they flow bottom-to-top. Samples and reagents are loaded in one configuration, and the chip is “slipped” to start the readout process.
The SlipChip design
Source: Nat. Commun. 3:1283 doi: 10.1038/ncomms2292 (2012).
Here’s how the authors describe it:
In the SlipChip, two pieces of glass etched with microfluidic wells and channels are assembled together in the presence of mineral oil. A fluidic path is formed when the two plates aligned in a specific configuration. Samples or reagents are preloaded through drilled holes using a pipette, and the top plate is then moved relative to the bottom plate to enable the diffusion and reaction of samples or reagents.
The team calls its device a “volumetric bar-chart chip,” or V-Chip. The V-Chip runs what’s called an ELISA (enzyme linked immunosorbent assay), which is the gold standard in biomarker quantitation tests. Normally ELISAs are read with some sort of instrument that can measure either color, fluorescence, or chemiluminescence. The V-Chip is far simpler (albeit, less quantitative).
It uses an enzyme called catalase to degrade hydrogen peroxide into oxygen gas in volumes proportional to the molecule of interest – in this case, hCG. That gas, in turn, forces a column of red dye upwards to a height determined by the hCG concentration. (See the V-Chip in action here.) The result is a easy to read, microfluidic bar graph, with the height of each bar indicating not only if a woman is pregnant, but just how much hCG is in her urine. In a comparison against a commercial home pregnancy test, the V-Chip was more sensitive at low hCG concentrations, and more accurate at very high concentrations.
The V-Chip’s design is flexible, the authors note, and can be used to test either a large number of samples for a single molecule (as might be done in a clinical trial) or a single sample for multiple molecules, as in cancer screening. The current design allows as many as 50 parallel fluidic channels, meaning up to 50 molecules could be tested in parallel. In one experiment, the team used a six-channel design to test a panel of breast cancer cell lines for the abundance of three proteins (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor) commonly found on breast cancer cells.
The simplicity of the test means it should be possible to design a device that can be used at home or in a doctor’s office. It is cheap, fast, and requires no special hardware. That means it could be used in areas lacking access to top-shelf medical care. It could even be used in the absence of a physician altogether. “The bar chart could be captured as an image using a smart phone, similar to a barcode reader and transmitted to a cloud computer for instant medical suggestions in the future,” the authors write. Now, how cool would that be?(*) That’s not entirely true. Harvard researcher George Whitesides has figured out a way to print microfluidic circuits onto paper, resulting in very simple and inexpensive designs. Boston-based Diagnostics For All is developing such tests for use in third world countries.
Jeffrey, a recovering scientist, has always had a passionfor the technology and the gadgetry of science. He has been ascientific writer and editor since 2000, when he left academia to jointhe staff of The Scientist magazine as a Senior Editor for Technology.Before that, he studied transcription factor biology at the Universityof Pennsylvania and Harvard Medical School -- training that,surprisingly, has little application in the real world. In 2006, heand his family headed west to Pocatello, Idaho, and has been afreelance writer ever since. You can see why Double X Science is thrilled to have him on the team! You can find Jeffrey at his Website or on Twitter at @j_perkel. Welcome, Jeff!]
It alarmed me because, well, I don’t like microbes much (despite, or perhaps because of my background in microbiology), and this article is about people getting very, very sick from sepsis (aka septicemia or bacteremia, an infection of the blood), which presents itself as a whole-body inflammatory response and a significantly increased risk of organ failure. It is an important area of microbiology because sepsis results from a bacterial infection, and the article says that 20% to 50% of infected patients die from sepsis.
My interest was piqued, however, because the piece goes on to talk about how a new genetic testing device that the US Food and Drug Administration approved in June could possibly help rein in the disease. That’s because it can reduce the time for diagnosing sepsis from days to hours. And when it comes to sepsis, time is critical.
Sepsis is confirmed by testing for the presence of specific types of bacteria in blood samples from patients and identifying what bacteria, if any, are in the circulation. If they are present, the researchers need to find out if the bugs are resistant to any antibiotic. Unfortunately, all that takes time – time the patient often doesn’t have. As the news story notes,
About the size of a small microwave oven, the Verigene Gram-positive Blood Culture Nucleic Acid Test is the first system approved by the FDA to identify quickly certain bacteria responsible for bloodstream infections — and whether some are resistant to the top drugs used against them.
Instead of the three days required for a traditional blood culture panel, results from the Verigene test come back within three hours, identifying up to a dozen specific bacteria known to cause sepsis, including strains of Staphylococcus, Streptococcus, Enterococcus and Listeria.
Of particular importance, the system can catch some particularly nasty bugs, methicillin-resistant Staphylococcus aureus (MRSA; see Maryn McKenna’s excellent Superbugif you really want to terrify yourself on this subject) and vancomycin-resistant Enterococci.
In its press release announcing the Verigene test’s approval, the FDA said that, compared to standard microbiology methods, the Verigene test results “were consistent with traditional blood culture methods in 93 percent to 100 percent of the comparisons.”
The test is remarkably simple, and even automated, requiring a dedicated sample processing instrument and a reader from Nanosphere.
The patient sample is added to a glass slide covered with capture signals that recognize DNA from sepsis-causing bacteria. The capture signals are placed on the glass slide in a defined order, each programmed to recognize only one strain of bacteria. This uniform order helps scientists identify which strain of bacteria, if any, is responsible for the infection. If the patient blood sample contains bacteria, the signals on the glass slide will capture its DNA, and the special scanner and software can detect this capture.
What sets the Verigene test apart from the previously available tests for sepsis is precisely how they do the detecting. The test adds sub-microscopic gold balls, called gold nanoparticles, to the glass slide. These gold nanoparticles are studded with more capture signals. When bacteria match up with the same specific capture signals, the nanoparticles will attach to that area. This ball gives scientists the ability to more rapidly detect which type of bacteria, if any, is present, and thus select the right course of antibiotic treatment.
The reaction is developed by coating the gold nanoparticles with silver, a process called signal amplification, which increases sensitivity up to 100,000 times, and then hitting it with light. Those spots containing the nanoparticles scatter light; those without it, do not. The effect is so strong, the original paper detected it using a “conventional flatbed scanner,” like something you’d have in your home office.
According to Nanosphere’s website, the whole thing requires less than five minutes’ worth of hands-on time, plus 2.5 hours to get the result. That falls within the necessary time frame to diagnose sepsis and begin life-saving antibiotic therapy.
Hopefully, this is a technology that neither your family nor mine will ever need. But it’s nice to know it’s there. And now, you know how it works.
(If you’re interested in the research paper that led to this test, from company cofounders Robert Letsinger and Chad Mirkin, both of Northwestern University, you can read it here.)
[Editor's note: I was on Twitter, as usual, a couple of days ago, and started seeing tweets with the hashtag #SSCAbc. They contained information that I, an avid consumer of science and medical information, don't normally see addressed in breast cancer stories, including for young women with breast cancer and how to talk to children about having breast cancer. I've aggregated some of those tweets below, but you can read more at the hashtag here, which represents the Seattle Cancer Care Alliance, whose representatives were conducting the Twitter session.]