Turing was right: Two proteins fit decades-old prediction

April 24, 2012 By Peter Reuell, Harvard University
“Turing was brilliant,” said Alexander Schier, professor of molecular and cellular biology. “There wasn’t a single molecule known that would regulate development or pattern formation when he proposed this model. For him, it was a pure mathematical model. Credit: Stephanie Mitchell/Harvard Staff Photographer

Today, Alan Turing is best known as the father of modern computer science, but in 1952 he sketched out a biological model in which two chemicals — an activator and an inhibitor — could interact to form the basis for everything from the color patterns of a butterfly’s wings to the black and white stripes of a zebra.

It was an innovative hypothesis, made all the more impressive by the fact that it was postulated without the benefit of modern molecular biology — the double-helix structure of DNA wouldn’t be discovered for another year.

Harvard research now shows that Nodal and Lefty — two proteins linked to the regulation of asymmetry in vertebrates and the development of precursor cells for internal organs — fit the described by Turing six decades ago. In a paper published online in Science April 12, Alexander Schier, professor of molecular and cellular biology, and his collaborators Patrick Müller, Katherine Rogers, Ben Jordan, Joon Lee, Drew Robson, and Sharad Ramanathan demonstrate a key aspect of Turing’s model: that the activator Nodal moves through tissue far more slowly than its inhibitor Lefty.

“That’s one of the central predictions of the Turing model,” Schier said. “So I think we can now say that Nodal and Lefty are a clear example of this model in vivo.”

Schier’s latest finding is the result of more than a decade of research into the Nodal/Lefty pairing. In a 2002 paper, his group described results that suggested the two proteins act as an activator/inhibitor pair, one of the key tenets of the model outlined by Turing. But it was the recent experiments on how the proteins move through tissue that clinched it.

To test the biophysical properties of Nodal and Lefty, Schier’s team began by generating modified versions of Nodal or Lefty that would fluoresce under laser light. They observed that Lefty moved farther through zebrafish embryos than Nodal.

To measure the diffusion rates of these proteins, they used a process called photobleaching to “erase” an area of either Nodal or Lefty. They then measured the time needed for Lefty and Nodal to diffuse into the bleached space. The results matched the prediction of the Turing model.

In a separate test, the researchers explored whether the two proteins might have different stabilities, which could also explain why Lefty moves farther through the embryo than Nodal. To test this possibility, researchers irradiated the modified versions of either Nodal or Lefty with lasers, causing the fluorescent proteins to change their color from green to red. By measuring how long it took for the red color to disappear, they were able to determine that Nodal and Lefty are similarly stable.

“That tells us that it’s the mobility not the stability that is different between these two molecules,” Schier said. “That’s important, because it is the diffusion that’s different in the models proposed by Turing.

“Turing was brilliant,” Schier continued. “There wasn’t a single molecule known that would regulate development or pattern formation when he proposed this model. For him, it was a pure mathematical model. The Turing equation is simple but there’s a certain beauty to it. It can be applied to many different biological systems and what you get are amazing and beautiful patterns. Our paper shows that aspects of the Turing model actually do work in vivo. We still don’t know how a zebra’s stripes or a leopard’s spots are formed, but the Turing model shows one way it could work.”

Going forward, Schier said, he hopes to understand the mechanism behind the different mobility of Nodal and Lefty. “We know these proteins are different, but why are they different?” Schier asked. “They are similar in size, they have similar structures – but somehow they must interact differently with other molecules, affecting how they move. That’s a question for the future.”

Explore further: Music in the air

Related Stories

Music in the air

August 22, 2011

The days of sitting at keyboard with a pencil and a sheet of manuscript paper to compose music could be long gone with the development of software by researchers from Monash University’s Faculty of Information and Technology ...

Alan Turing's 1950s tiger stripe theory proved

February 19, 2012

Researchers from King's College London have provided the first experimental evidence confirming a great British mathematician's theory of how biological patterns such as tiger stripes or leopard spots are formed.

Therapeutic potential of embryonic stem cells

June 18, 2010

Are stem cells ready for prime time? The therapeutic potential of embryonic stem cells has been an intense focus of study and discussion in biomedical research and has resulted in technologies to produce human induced pluripotent ...

Designer roots to counter drought

July 12, 2011

Recent discoveries by a University of Queensland agricultural scientist provide the basis for custom designing plant roots. Her discovery is already being used by plant breeders to develop drought-resistant sorghum crops.

Scientists pioneer new method for watching proteins fold

December 22, 2011

(PhysOrg.com) -- A protein’s function depends on both the chains of molecules it is made of and the way those chains are folded. And while figuring out the former is relatively easy, the latter represents a huge challenge ...

Recommended for you

Digging deep into distinctly different DNA

January 22, 2018

A University of Queensland discovery has deepened our understanding of the genetic mutations that arise in different tissues, and how these are inherited.

Computational method speeds hunt for new antibiotics

January 22, 2018

A team of American and Russian computer scientists has developed an algorithm that can rapidly search massive databases to discover novel variants of known antibiotics—a potential boon in fighting antibiotic resistance.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.