The other day I was learning a dance choreography from a good friend of mine. She was having trouble remembering which combination went where, because the song repeats itself many times, and it's hard to know "where" in the song you are just by hearing a clip.
It struck me that this challenge was not unlike the challenge that scientists face trying to assemble genomes. Genomes often contain repeat regions: stretches of sequence that are repeated in other parts of the genome. In a way, repeat regions are like the chorus of a song. When you hear a clip of only the chorus, you might not know if it's at the beginning of the song, somewhere in the middle, or near the end.
The trick with dancing a choreography that has lots of repeats is to memorize the bit that comes right before and right after each repeat. Those bits help knit the repeat to its correct position in the song. Genome assemblers can do the same thing if they receive sequences containing a bit of flanking DNA along with the repeat region. Then each genetic chorus has its proper context.
Wednesday, August 29, 2012
Saturday, April 14, 2012
Short Stories and Novels
When you get right down to it, your genome--the sum total of your DNA--is a story. Sure, it's not written in English: DNA has its own code, with far fewer letters than we humans use to describe our world. Yet this one code describes organisms as complex as ourselves and as elegantly simple as a virus. As someone working in the field of DNA sequence analysis, I am thrilled to live in an age when whole genome sequencing is not only possible, it's becoming faster and cheaper by the year. Still, the process of determining an entire genome is quite the puzzle.
I want you to imagine your genome is right in front of you. Maybe it's a big, leatherbound tome or a crisp, new paperback. In a perfect world, you would just open the book and read it, cover to cover. But the challenge of DNA sequencing is that the current technology can't do that, yet. Instead of reading your genome cover to cover, you can only see, for example, 10 words at a time. Somehow, you have to put the story back together.
If someone gave you an envelope with the fragments of a haiku in it, you could probably paste the whole thing together all on your own. But if someone hands you a shoebox with "The Cat in the Hat" fragments instead, it might take you a bit longer to put together. And what if someone delivers you an office space filled with boxes of a hefty Stephen King novel, eh? You'd probably need alot of time and alot of help.
Bigger stories mean bigger problems. That is the challenge of sequencing a genome, in a nutshell. There are plenty of things that make the problem more difficult. For example:
I want you to imagine your genome is right in front of you. Maybe it's a big, leatherbound tome or a crisp, new paperback. In a perfect world, you would just open the book and read it, cover to cover. But the challenge of DNA sequencing is that the current technology can't do that, yet. Instead of reading your genome cover to cover, you can only see, for example, 10 words at a time. Somehow, you have to put the story back together.
If someone gave you an envelope with the fragments of a haiku in it, you could probably paste the whole thing together all on your own. But if someone hands you a shoebox with "The Cat in the Hat" fragments instead, it might take you a bit longer to put together. And what if someone delivers you an office space filled with boxes of a hefty Stephen King novel, eh? You'd probably need alot of time and alot of help.
Bigger stories mean bigger problems. That is the challenge of sequencing a genome, in a nutshell. There are plenty of things that make the problem more difficult. For example:
- What if your "story" is a poem with repeated phrases? How do you know where to put the fragment that matches 6 different places?
- What if, instead of seeing 10 words at a time, you could see 20 but there would be lots of typos?
- What if the story is so huge it would take you several lifetimes to put together on your own?
- What if I gave you a draft copy of your story, and had you match the fragments to the draft?
- What if I gave you a roomful of interns to help?
- Or better yet, what if I gave you a roomful of computers to help?
Tuesday, January 26, 2010
Quorum call, without voices
Is there anybody out there?
When it comes to political intrigue, it’s important to know whether you stand united or alone. Are you surrounded by friends or enemies? Is it time to lead the charge or wait for reinforcements? Tallying how many supporters you have—or how many enemies are waiting in your midst—can be critical to your success.
For bacteria, things aren’t much different. Bacteria survey their surroundings for others of their kind, and others NOT of their kind. They may wait until they have sufficient numbers to launch an attack on your body, or to coordinate effective mining of a nutrient source. But bacteria don’t have eyes, ears, or a mouth; they cannot see, hear, or speak. So how do they tell who is out there?
The peril of the tennis ball
Time to use your imagination, folks. Imagine you are in a windowless room. The door is closed. You are wearing a blindfold and earplugs. You cannot speak. In your hand is a fuzzy tennis ball. When you throw the tennis ball, it bounces off the walls until, eventually, it stops. Think about the chances of the ball ricocheting off a wall and hitting you in the head.
Now remember: you cannot speak, you cannot hear, you cannot see. But, if I put another person in the room with a tennis ball to throw, do you think you’d be able to tell you were not alone in the room? Maybe. How about if I dropped in TEN people, each with one tennis ball? How often do you think you’d be smacked square in head?
It probably seems strange to imagine all this blindfolded tennis ball throwing, and I’m pretty sure it won’t give you a better understanding of human politics. But if you understand how you’d be able to sense the presence of more people in the room based on how often you got a tennis ball concussion, you understand the microbial behavior called quorum sensing.
Bacteria don’t throw tennis balls, they “throw” chemical signals
The tennis ball in our thought-experiment represents a quorum-sensing signal. These are chemical compounds that bacteria can “throw” out into the environment, and “catch” if they hit the cell. In this way, bacteria can sense if they are relatively alone, or if they are surrounded by thousands of others.
If you play around with the tennis ball room scenario, you can start to envision more complex issues with quorum sensing. Can you imagine ways to trick the bacteria into thinking they were not alone? Or trick a crowd of bacteria into thinking they were all alone?
When it comes to political intrigue, it’s important to know whether you stand united or alone. Are you surrounded by friends or enemies? Is it time to lead the charge or wait for reinforcements? Tallying how many supporters you have—or how many enemies are waiting in your midst—can be critical to your success.
For bacteria, things aren’t much different. Bacteria survey their surroundings for others of their kind, and others NOT of their kind. They may wait until they have sufficient numbers to launch an attack on your body, or to coordinate effective mining of a nutrient source. But bacteria don’t have eyes, ears, or a mouth; they cannot see, hear, or speak. So how do they tell who is out there?
The peril of the tennis ball
Time to use your imagination, folks. Imagine you are in a windowless room. The door is closed. You are wearing a blindfold and earplugs. You cannot speak. In your hand is a fuzzy tennis ball. When you throw the tennis ball, it bounces off the walls until, eventually, it stops. Think about the chances of the ball ricocheting off a wall and hitting you in the head.
Now remember: you cannot speak, you cannot hear, you cannot see. But, if I put another person in the room with a tennis ball to throw, do you think you’d be able to tell you were not alone in the room? Maybe. How about if I dropped in TEN people, each with one tennis ball? How often do you think you’d be smacked square in head?
It probably seems strange to imagine all this blindfolded tennis ball throwing, and I’m pretty sure it won’t give you a better understanding of human politics. But if you understand how you’d be able to sense the presence of more people in the room based on how often you got a tennis ball concussion, you understand the microbial behavior called quorum sensing.
Bacteria don’t throw tennis balls, they “throw” chemical signals
The tennis ball in our thought-experiment represents a quorum-sensing signal. These are chemical compounds that bacteria can “throw” out into the environment, and “catch” if they hit the cell. In this way, bacteria can sense if they are relatively alone, or if they are surrounded by thousands of others.
If you play around with the tennis ball room scenario, you can start to envision more complex issues with quorum sensing. Can you imagine ways to trick the bacteria into thinking they were not alone? Or trick a crowd of bacteria into thinking they were all alone?
Monday, January 25, 2010
Microbial Grappling Hooks
It's a common theme for my view of microbes: for many real-world problems, microbes have already developed a solution.
Want to turn biomass into fuel? Microbes can do it!
Want to seed clouds for rain? Microbes can do it!
Want to move around using a grappling hook? Microbes can do it!
I've had the honor of contributing a blog entry to the delightful blog "Small Things Considered" on the topic of microbial grappling hooks, known more technically as "Type IV pili." It's basically a rope or filament that is sticky at the end. The bacteria can extend this filament out of the cell, and if the sticky end catches on something the microbe can pull itself along by reeling the filament back in. This is just one of many fascinating structures bacteria can use to interact with the world around them.
If you want a little more technical detail on how Type IV pili work, check out my "Small Things Considered" blog entry on the subject!
Want to turn biomass into fuel? Microbes can do it!
Want to seed clouds for rain? Microbes can do it!
Want to move around using a grappling hook? Microbes can do it!
I've had the honor of contributing a blog entry to the delightful blog "Small Things Considered" on the topic of microbial grappling hooks, known more technically as "Type IV pili." It's basically a rope or filament that is sticky at the end. The bacteria can extend this filament out of the cell, and if the sticky end catches on something the microbe can pull itself along by reeling the filament back in. This is just one of many fascinating structures bacteria can use to interact with the world around them.
If you want a little more technical detail on how Type IV pili work, check out my "Small Things Considered" blog entry on the subject!
Thursday, December 31, 2009
Nature wins by a hair
When I first started doing lab work, I found all the specialized equipment quite glamorous. Especially the cold room—basically a walk-in fridge—which always billowed out fog when you opened the door and reminded me very much of the embryo storage room in Jurassic Park. In my lab, we’ve got centrifuges large and small, precision pipettors for measuring out droplets of chemicals, and lots of vials and beakers. In fact, there are whole companies focused on providing labs like ours with expensive, specialized equipment.
But if you look closely in every lab, you’ll find very normal items pressed into scientific service. After all, we scientists are in the business of innovation. In fact, some tools are actually the result of Mother Nature’s innovation, not ours. My favorite examples of nature-made scientific tools are cat whiskers and human eyelashes.
Some scientists study proteins by crystallizing them. One of the challenges of this approach can be getting BIG crystals to form. So sometimes big crystals are formed by micro-seeding a solution with smaller crystals. This requires a very small implement to pick up that small crystal (seed crystal). To this day, scientists sometimes use cat whiskers for the task. They are fine enough to grab a small crystal as you drag the whisker through the solution.
Another set of researchers works on the tiny nematode (worm-like creature) Caenorhabditis elegans. When your research subject is the about the size and length of an eyelash, how do you poke, prod, and transfer such a creature? With a human eyelash, that’s how.
It is a bit humbling that, despite all the sophisticated lab equipment available, sometimes the best tool for the job is something nature created!
But if you look closely in every lab, you’ll find very normal items pressed into scientific service. After all, we scientists are in the business of innovation. In fact, some tools are actually the result of Mother Nature’s innovation, not ours. My favorite examples of nature-made scientific tools are cat whiskers and human eyelashes.
Some scientists study proteins by crystallizing them. One of the challenges of this approach can be getting BIG crystals to form. So sometimes big crystals are formed by micro-seeding a solution with smaller crystals. This requires a very small implement to pick up that small crystal (seed crystal). To this day, scientists sometimes use cat whiskers for the task. They are fine enough to grab a small crystal as you drag the whisker through the solution.
Another set of researchers works on the tiny nematode (worm-like creature) Caenorhabditis elegans. When your research subject is the about the size and length of an eyelash, how do you poke, prod, and transfer such a creature? With a human eyelash, that’s how.
It is a bit humbling that, despite all the sophisticated lab equipment available, sometimes the best tool for the job is something nature created!
Thursday, December 17, 2009
Our bodies, ourselves, our microbial ecosystems
Winter has finally and unquestionably hit Madison, hard. Staring out at the wintry landscapes I’ve been reminded of how harsh and ever-changing a smaller set of landscapes—our bodies—can be.
Just as we live on a planet with different terrains and environments, microbes live on, and in, the human body. As you can imagine, some areas of your body are more forgiving than others. Your mouth is a great place to get food, but with all that saliva it can be hard for a microbe to STAY there. Your skin can be welcoming where it is moist (like your armpits or between your toes) but challenging where it becomes a dry, cragged desert around your elbows. And of course, there is your digestive tract, a warm, nutrient-rich home for millions of microbes.
Though all this probably sounds a bit creepy and makes you want to take a shower, please remember that living with microbes is the healthy norm. They were here long before we arrived on the scene: my friend Dr. Mark O. Martin has a saying about this: “First to evolve, last extinct” I believe. But I digress!
When it comes down to sheer numbers, scientists have estimated that in your body there are ten times as many bacterial cells as human cells. Another motto comes to mind: “You are born 100% human and will die 90% bacteria.”
So, who are all these microbes are and what are they doing with our bodies?
A new National Institute of Health (NIH) “roadmap initiative” aims to answer this question, or at least BEGIN to answer this question, with The Human Microbiome Project. Scientists across the country will be sampling various sites on the bodies of healthy and diseased individuals to ask “who’s there?” and “what are they doing?” Along the way, we may get some interesting insight into how much our microbes very from body site to body site, person to person, week to week, state to state . . . you get the picture!
Just as we live on a planet with different terrains and environments, microbes live on, and in, the human body. As you can imagine, some areas of your body are more forgiving than others. Your mouth is a great place to get food, but with all that saliva it can be hard for a microbe to STAY there. Your skin can be welcoming where it is moist (like your armpits or between your toes) but challenging where it becomes a dry, cragged desert around your elbows. And of course, there is your digestive tract, a warm, nutrient-rich home for millions of microbes.
Though all this probably sounds a bit creepy and makes you want to take a shower, please remember that living with microbes is the healthy norm. They were here long before we arrived on the scene: my friend Dr. Mark O. Martin has a saying about this: “First to evolve, last extinct” I believe. But I digress!
When it comes down to sheer numbers, scientists have estimated that in your body there are ten times as many bacterial cells as human cells. Another motto comes to mind: “You are born 100% human and will die 90% bacteria.”
So, who are all these microbes are and what are they doing with our bodies?
A new National Institute of Health (NIH) “roadmap initiative” aims to answer this question, or at least BEGIN to answer this question, with The Human Microbiome Project. Scientists across the country will be sampling various sites on the bodies of healthy and diseased individuals to ask “who’s there?” and “what are they doing?” Along the way, we may get some interesting insight into how much our microbes very from body site to body site, person to person, week to week, state to state . . . you get the picture!
Thursday, November 19, 2009
It always comes back to Jurassic Park, doesn't it?
I just got back from a seminar by George Weinstock of Washington University, St. Louis about the human microbiome project. I was planning on doing a blog entry on the human microbiome project--and still will write one--but during the talk I was struck by the amount of data the Wash. U. genome sequencing center was producing, and how a huge percentage of the talk centered on the challenges of storing and processing all that data.
For example, the center needs an additional 4 terabytes of storage each day. They've built an entire storage facility which is in great part air conditioners and electrical equipment to maintain the data storage. It uses the same amount of electrical power it takes to light a New York Skyscraper.
It made me think back to all those Cray supercomputers used to process the ancient dinosaur DNA sequences in that most-influential novel "Jurassic Park" by the late Michael Crichton. The speed of current DNA sequencing technology is blinding in comparison to what those ol' Cray computers would have been capable of. But though the speed of the sequencing has gotten faster, all that data requires a huge space to house the technology to store it.
For example, the center needs an additional 4 terabytes of storage each day. They've built an entire storage facility which is in great part air conditioners and electrical equipment to maintain the data storage. It uses the same amount of electrical power it takes to light a New York Skyscraper.
It made me think back to all those Cray supercomputers used to process the ancient dinosaur DNA sequences in that most-influential novel "Jurassic Park" by the late Michael Crichton. The speed of current DNA sequencing technology is blinding in comparison to what those ol' Cray computers would have been capable of. But though the speed of the sequencing has gotten faster, all that data requires a huge space to house the technology to store it.
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