Published by the Students of Johns Hopkins since 1896
September 21, 2021

Dialogues in Research: DNA origami and labyrinths

By KRITI BOMB | February 20, 2020

COURTESY OF SAKUL RATANALERT These are examples of the types of DNA origami nanostructures that can be designed.

Sakul Ratanalert, a lecturer in the department of Chemical and Biomolecular Engineering at Hopkins, focuses his research on a specific type of DNA nanostructure referred to as DNA origami. 

Ratanalert’s PhD focus was in the area of DNA nanotechnology, and like its namesake hobby, DNA origami was a source of creativity and ingenuity throughout his work. DNA has four kinds of nucleotides — A, T, C and G — that form a kind of alphabet which arranges in a double helix, similar to words in a sentence. 

Unlike in the field of genetics, DNA nanotechnology focuses on DNA’s molecular properties rather than its genetic role. For example, one of the benefits of DNA is its ability to self-assemble and serve as material for nanoparticles that can be engineered as needed. 

Ratanalert explained this concept of self-assemblage in the context of DNA origami in an email to The News-Letter.

“DNA origami is composed of two strands: the scaffold strands, which are ten nucleotides long, and staple strands, which are fifty nucleotides long. The two ends of a staple strand can bind to separate regions of the scaffold strand causing it to fold into a loop.”

The result, he says, reminds him of the ancient Japanese paper folding art. 

“When all the staples bind properly, the scaffold strand is folded into the desired shape, much like how the proper folds on a piece of paper can form an origami crane, resulting in a structure much larger and more intricate than a simple double helix,” he wrote.

This phenomenon is even more intricate than it sounds, a highly-complex version of the origami tutorial videos we are all familiar with. 

Ratanalert’s research has many uses in the field of chemical and biological engineering.

For example, as he detailed, in the field of drug delivery, DNA origami can be used to create a cage with the inside structure containing the drug that needs to be delivered to a particular type of cell and the outside structure decorated with carefully positioned protein markers that allow the correct cell to identify it and take it in. 

While seemingly full of the potential to serve a multitude of functions, the field of DNA origami is still a relatively new area of nanotechnology that is being researched. 

Ratanalert’s research focused specifically on making DNA origami predictions through tested algorithms rather than arriving at the answer through trial and error.

“One core part of my PhD work was creating a specific software that could take in information about the 3D geometry a user wanted and produce the list of DNA sequences that, when synthesized and mixed, would produce the desired nanostructures,” he wrote. 

The nanostructures are called DAEDALUS (DNA Origami Sequence Design Algorithm for User-defined Structures) which is an homage to the mythical Greek architect of the Labyrinth and reflects the software’s ability to calculate the scaffold strand’s path through the desired geometry.

Along with continuing the development of DAEDALUS and further research into the thermodynamics of DNA origami and self-assembly, Ratanalert aims to teach and involve more students in this whirlwind of modern mythology, nanotechnology and pedagogy. 

Over the summer, he hopes to create more user-friendly programs with which students can interact with concepts like a sandbox, letting the computer do some of the equation-solving for them. 

One of Ratanalert’s main objectives in doing so is to bridge what he sees as a gap between mathematical calculations and conceptual understanding. 

“I have found that my students are great at solving large systems of equations but translating the alphabet soup of variables to have physical meaning can sometimes be challenging,” he wrote. 

In his classes, he uses a specific way of testing to see if students understand the meaning and relationships within the alphabet soup of different variables. 

“One of my favorite qualitative questions to ask is, ‘If X increases, does Y increase, decrease or stay the same?’” he said. 

He went on to describe how students can learn new information from this project, and linked the equations to scientific principles. 

“By using the equations, students can easily figure it out, but what is important is that the students learn how and why X and Y are related, which requires a deeper understanding of the engineering, physical and chemical concept,” he said. 

Ratanalert hopes that such teaching programs can help students focus on how variables change in response to one another, building their logical reasoning and intuition in the process, an important skill for future researchers. 

Moreover, he is actively looking for students to help out with the development of such programs. Ratanalert hopes to be able to contribute back to his engineering education community through this new initiative. 

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