Sudoku-solving bacteria

Dec 01 2010 Published by under Biology & Environment

One of the goals of synthetic biology is to engineer bacteria into biological "machines" that can be used to produce energy, deliver drugs, or synthesize materials. If the engineered bacteria could selectively communicate with each other, would expand their possible uses.

A team of students from the University of Tokyo decided to create E. coli bacteria that could selectively communicate with each other for this year's Internationally Genetically Engineered Machine (iGEM) competition, held last November 6-8 at MIT.

Sudoku Puzzle

Sudoku Puzzle

As a proof-of-principal for their bacterial communication system, the Japanese team created microbes that could solve a Sudoku puzzle.

Sudoku puzzles are usually made from a 9x9 grid made up of nine 3x3 squares. The numerals 1 through 9 can only be used once in each row, once in each column, and once in each 3x3 square. The puzzles start out with some of the numbers already filled in, and the goal is to fill in the blanks. You can see an example of a starting grid over on the right -->

Even though a Sudoku puzzle uses numbers, it's not a math puzzle - no adding, subtracting or other number manipulation is required. It's a logic puzzle. It could work just as well with nine different pictures or nine different letters or nine different colors.

The simple logic rules of the game were an ideal way to demonstrate the ability of the modified bacteria to communicate.

The Japanese team's modified bacteria were designed to solve a 4x4 Sudoku grid.  They engineered 16 genetically different bacteria, one for each spot on the grid. Each of those strains of bacteria has the ability differentiate into one of 4 types. Each of those types can then direct "detection bacteria" to produce a corresponding fluorescent color.

Just like any Sudoku puzzle, the grid begins with some of the squares already solved, like this:

E.Coli Sudoku Puzzle

The differentiated bacteria produce signals that tell the other bacteria their type. The undifferentiated bacteria are able to detect which of the 4 types are already present in the same "row",  "column" and "block", while ignoring information from irrelevant "squares". For example, undifferentiated bacteria representing square 4 would need to detect which differentiated types were already present in squares 1-3 (the same row), squares 8, 12, and 16 (the same column), and squares 3, 7 and 8 (the same block).  They would have to ignore the bacteria in irrelevant squares 11 and 13.

Here is their video of how the system works, which is a bit clearer than my explanation:

The students already have figured out - at least theoretically - how to modify their system so that bacteria would be able to solve a 9 x 9 Sudoku grid.

But that isn't the only use of such engineered microbes. Bacteria that can differentiate between relevant and irrelevant communications could ultimately be used to design bacterial logic circuits for parallel calculation devices. Maybe someday we'll be able to use bacteria to plug away at difficult computing problems.

You  can read the technical details to learn more about the biochemistry of the system.

And if you want to test your own Sudoku skills, I recommend the daily puzzle here.

(Project via New Scientist)


Top image: A Sudoku layout generated by the GNU programSu Doku Solver and contributed in the public domain by Lawrence Leonard Gilbert. From Wikipedia.
Bottom Image: "16 kinds of E. coli corresponding to each cell" by the UT Tokyo iGEM team, shared under a Creative Commons Attribution-ShareAlike license.

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Women's Health: What's in Your Tap Water? (Part 1 of 3)

Sep 27 2010 Published by under Biology & Environment

Water, water, water

At the suggestion of Scicurious, a bunch of us at Scientopia have decided to take a closer look at the science - both good and bad - behind the articles in the latest issue of Women's Health magazine. Be sure to check out the Scientopia front page where you can find all the Women's Health review posts

We're suffering from a heat wave here in Southern California.  Today the temperature is expected to hit triple digits by mid-afternoon, while the relative humidity is expected to drop to a dry 10%. Dehydration is a serious concern, especially for people who have to spend time outside during the hottest part of the day. It's a lifesaver that clean water is as close as the nearest faucet.

That brings me to the article1 in Women's Health that asks "Think that's clean water coming out of your faucet?" The answer, of course, is that there are a "host of nasties" we should be concerned about. It lists four pollutants that may be found in your tap water: chlorine, lead, bacteria, and hormone and drug by-products, that has a take-home message that we should be very concerned about the toxins in the water we drink.

So should we avoid drinking water from the faucet? or is it scare-mongering? While there are indeed legitimate concerns about the safety of the water supply, I'd say the short piece makes it sound as if contaminated tap water is a much greater problem than it really is.

Water Treatment Cycle (click for details)

There is no one single source of tap water in the United States2. There are more than 150,000 public water systems in the US, supplying drinking water to the vast majority of Americans. The quality of the water varies depending on the source and the efficiency of local water treatment. But even so, the public drinking water supply is required to meet the safety standards overseen by the  Environmental Protection Agency.

So what do we actually know about the "nasties" in our water supply?  Read on.

Nasty Chlorine

In 1908 Jersey City, New Jersey became the first municipal water system in the United States to disinfect its water supply with chlorine. The treatment is very effective at killing bacteria, viruses, and parasites. Today, a century later, disinfection of drinking water has virtually eliminated water-borne diseases like cholera and typhoid fever in the U.S.

The problem is that in addition to killing pathogens, chlorine can chemically react with organic compounds in the water, creating toxic by-products, particularly trihalomethanes (THM). Those are the the "nasties" that the article refers to:

But studies show that long-term exposure to chlorine by-products can lead to miscarriage or birth defects, says Gina Solomon, M.D., a senior scientist at the Natural Resources Defense Council.

That's scary!  But how great is the actual risk?

A search of the recent medical literature turns up some studies that found a relationship between exposure to chlorination by-products and birth defects, and others not so much.  A recent review of the literature found that isn't enough evidence to conclude that the by-products create a significant risk of birth defects.  A  different review, looking at a slightly different set of studies did find a moderate association between chlorination by-products and miscarriages, particularly in women who drink five or more glasses of tap water per day.

So there may be a small risk of drinking tap water during pregnancy. Fortunately, many public water suppliers have begun to use chloramine, rather than chlorine, as a disinfectant. That reduces the total level of disinfection by-products, which is step in the right direction.

You can also help remove the contaminants yourself. Most of the chlorination by-products are volatile, meaning that they will eventually evaporate. The Women's Health article suggests letting the water stand 5 minutes before drinking, but that doesn't seem like nearly long enough to make a difference. The World Health Organization suggests boiling for 5 minutes to remove THM.  You'd probably have to let the water stand at room temperature for several hours to have the same effect.

And if you are seriously concerned, don't forget that showering, bathing and swimming in chlorinated pools likely also contribute to trihalomethane exposure.

Further reading:

Nieuwenhuijsen MJ et al. Chlorination Disinfection By-Products in Drinking Water and Congenital Anomalies: Review and Meta-Analysis. Environ Health Perspect. 2009 October; 117(10): 1486–1493. doi: 10.1289/ehp.0900677.

Bove F. et al. Drinking water contaminants and adverse pregnancy outcomes: a review. Environ Health Perspect. 2002 February; 110(Suppl 1): 61–74. (full text)

Environmental Protection Agency: Basic Information about Disinfection Byproducts in Drinking Water: Total Trihalomethanes, Haloacetic Acids, Bromate, and Chlorite

World Health Organization:  Trihalomethanes in drinking-water (pdf).

Nasty Bacteria

Scanning electron micrograph of E. coli.

Treatment of water with chlorine or other disinfectants kills the microbes that can make you sick. But sometimes water isn't adequately treated and pathogens can end up in your drinking water. Or as Women's Health put it:

Gnarly bacteria like E. coli can make their way into water from human and animal waste that runs into reservoirs from broken pipes and sewage systems.

E.coli infection is spread through ingestion of poop from infected animals or humans, and it can indeed be spread through drinking contaminated water, as well as eating contaminated or by contact with infected individuals. However, it's rare that it finds its way into the water coming out of your tap. Let's look at some numbers.

According to the CDC, in 2005 and 2006 there were a total of 20 disease outbreaks associated with drinking water in the U.S., affecting 612 people. To put that into perspective, that is about 300 people affected by drinking water-associated disease outbreaks per year out of a total U.S. population of roughly 300 million. Even factoring in the likelihood that some small outbreaks went unreported, such outbreaks are rare.

Twelve of those twenty outbreaks - affecting 135 people -  were associated with bacterial contamination. Ten were caused by Legionella in contaminated building plumbing systems; one outbreak was caused by Campylobacter, and a single outbreak was caused by pathogenic E. coli.  The E.coli outbreak affected 60 people at a camp in Oregon that was supplied with inadequately chlorinated river water.

It looks to me that as long as your local water treatment facility is functioning properly, the risk of infection from drinking tap water is extremely low.

Of course for someone who has a compromised immune system or is otherwise vulnerable to infection, even a small risk can pose a danger. Fortunately there is an easy solution: boiling water before drinking it should kill any microbes lurking within.

Further reading:

CDC Morbidity and Mortality Weekly Report Surveillance Summary:  Surveillance for Waterborne Disease and Outbreaks Associated with Drinking Water and Water not Intended for Drinking --- United States, 2005--2006 (pdf version)

Tomorrow: Lead and pharmaceuticals.


1. It's actually not so much an article as a "List Tool", that breaks down a topic into 4 or 6 or 8 pithy points.

2. Women's Health is a U.S. magazine, so I'm assuming they are referring to the U.S. water supply.

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Glass Microbes and Colorless Viruses

Aug 19 2010 Published by under Art & Science

Electron micrograph of the 2009 H1N1 influenza virus

3D representation of the influenza virus

Look at the two images of the H1N1 influenza virus - the strain that causes swine flu - on the right.

The first is a three-dimensional illustration that shows different parts of the virus in different colors  - the hemagglutinin protein on the surface is blue, for example, while the RNA and associated proteins inside the virus are green.

The second is an electron micrograph image of the same virus. It's a more "realistic" depiction of the influenza virus than the 3D illustration, but it has been artificially colored.

UK artist Luke Jerram was intrigued by the fact that both types of images false in their own way. To explore how artificial coloring can affect our understanding, he worked with University of Bristol virologist Andrew Davidson to create  a series of clear glass sculptures that accurately depict different viruses including the influenza virus, HIV, SARS and smallpox.

Here is Jerram's sculpture of the H1N1 influenza virus:

As he explained in an interview with the Wellcome Trust:

The series is a reflection of my interest in how images of phenomena are represented and presented to the public. I’m colour blind and this has given me a natural interest in exploring the edges of perception.

Often images of viruses are taken in black and white on an electron microscope and then they are coloured artificially using Photoshop. Sometimes that will be for scientific purposes but other times it will be just to add emotional content or to make the image more attractive.

The problem is that you end up with the public believing that viruses are these brightly coloured objects. These are often portrayed in newspapers as having an air of scientific authenticity and objective truth, whereas actually that isn’t the case. You can end up with some images that potentially promote fear.

Smallpox, HIV and Untitled glass virus sculptures

Swine Flu Sculpture

Glass swine flu sculpture by Luke Jerra

I think Jerram's virus sculptures are quite beautiful. However, they don't make the viruses any more or less frightening - or real - to me.

What do you think?

The first two images are from the CDC Newsroom Image Library. The illustration is by Dan Higgins, CDC. The electron micrograph is by C. S. Goldsmith and A. Balish, CDC.

Glass virus photographs by Luke Jerram.

Thanks to Chris for sharing the link to Jerram's web site!

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E. chromi and The Scatalog

Aug 17 2010 Published by under Brain & Behavior

This is for the new "Carnal Carnival". This month's theme is poop, and will be hosted by Bora at a Blog Around the Clock.

Pigments produced in "E. chromi"

E. coli Bacteria engineered to produce different pigments by a team from Cambridge for iGEM 2009

The International Genetically Engineered Machine competition (iGEM) is an annual contest in which student teams use a kit of "standard biological parts" to engineer bacteria with new and interesting properties.

There were 110 teams entered in the 2009 iGEM competition. Finalists included Valencia's  "bio-screen" lighting display and Groningen's heavy metal scavengers for cleaning polluted water. You can find information about all the team submissions on the official web site.

The winner of the competition was the Cambridge team, for their development of "E. chromi": bacteria engineered to express a rainbow of different colored pigments. Although the bacteria are colorful enough be used to create bacterial art, they were designed to be environmental sensors.

Displaying the Scatalog

Displaying the Scatalog at the iGEM2009 Jamboree

So what does that have to do with poop? The Cambridge iGEM team collaborated with designers Daisy Ginsberg and James King - who both use biotechnology in their art - to brainstorm potential applications for their design. One of the possibilities they came up with was The Scatalog, which proposes to use pigment producing bacteria for inexpensive personal disease monitoring.

The idea is pretty simple:  eat some tasty yogurt containing  E. coli bacteria  engineered to secrete different colored pigments in the presence of specific chemical signals. E. coli are a normal part of your intestinal flora, so the bioengineered bacteria should be able to colonize your gastrointestinal tract. In a healthy system, only one color - say blue - would be produced, resulting in blue poop. Any chemical changes in your system, such as exposure to toxins or development of a disease, would cause your poop to change color.  Just match your poop color to the reference turds in the Scatalog and you get an instant health assessment.

You can see close-ups of the Scatalog in Guerilla Science's photostream.

Sadly, the Scatalog hasn't been developed beyond its colorful plastic poo samples.  As experts  have pointed out, it may turn out to be too impractical to be implemented:

"I can see the popular appeal of this kind of E. chromi technology," said Rick Henrikson, who helps run the Point-of-Care Diagnostics Idea Lab at the University of California, Berkeley. "But as far as actual diagnostics, conceptually it's a little far off." Developing such a product, he explained, would require huge feats: getting the Food and Drug Administration to approve it, for example, and keeping the body's immune system from attacking the bacteria.

What a party pooper!

Here's a video of the creators explaining the project (there is unfortunately a lot of background noise that makes the audio a bit difficult to understand.):

Video: Jam09 05 - E.chromi interview with Daisy Ginsberg and James King from mac cowell on Vimeo .
Top image: Bacteria producing different pigments created by Team:Cambridge for iGEM 2009

Bottom image: Scatalog display at iGEM2009 Jamboree, taken by jimhaseloff on Flickr and shared under a Creative Commons Attribution-NonCommercial license.

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