Special EF-X: Professor Hekstra wins NIH Director’s New Innovator Award

October 8, 2020
Protein tug of war

Each cell in your body contains a world bustling with activity. The bustlers? Proteins. Proteins are the molecular structures that build and run cellular operations. They act as scaffolds and traintracks. They form gates and tunnels. They walk, pinch, pull, bend, and squeeze. Through these mechanical and chemical processes, they keep us alive and healthy.

Over the last 50 years, scientists have come to understand the chemical life of proteins. However, the mechanical life of these molecular machines has remained elusive. Proteins are exceedingly small. Understanding how they bend, twist, snap, and curl means watching them moving at the atomic level. This has not traditionally been possible.

The Hekstra lab at Harvard is changing that. Doeke Hekstra, assistant professor of Molecular & Cellular Biology and of Applied Physics, has pioneered a new technique which gives us our first insights into the atomic-scale biomechanics of proteins. The technique – called electric field-stimulated X-ray crystallography (EF-X) – allows scientists to watch proteins move at the atomic scale.

“Our vision is to be able to systematically map the effective physical and mechanical properties of proteins, by pushing and pulling on atoms and seeing their response,” Hekstra says. “Ultimately, we hope to understand how proteins work and how their evolution is shaped by their physics.”

How can you push and pull on atoms? The secret to the technique is in the proteins themselves. Proteins are necklaces of amino acid beads that curl themselves up into elaborate 3D structures. However, not all the beads are the same. “Electrically, amino acids only have three personalities – positive, negative, or neutral,” says Dr. BN Queenan, Executive Director of Research at Harvard’s NSF-Simons Center. “In an electric field, that’s all you need to know: these ones will come, those will stay, and those will go. We’ve known that for over 150 years. But only in the last 5 has Doeke figured out how to use those personalities to map proteins.”

“If I apply an electric field to a point charge, it will go whizzing off into the distance,” says Maggie Klureza, a Ph.D candidate in Chemistry & Chemical Biology in the Hekstra group. “But in a protein, it’s more interesting. A charged amino acid can try to go whizzing off, but it’s attached to the larger molecular structure and so its movements will be constrained. With EF-X, we can use electric fields to push or pull on a charge and use X-ray crystallography to see which parts of the protein move along with it.”

Now, with the prestigious NIH Director’s New Innovator Award, Hekstra and his lab are able to scale up this vision. The NIH’s New Innovator Award recognizes young professors for their out-of-the-box approaches to biological questions, giving them $1.5M to help realize their dream.

“I want to acknowledge all the support from the MCB, qBio, and SEAS community,” says Hekstra. “Their passion, drive, and sense of community have pushed me forward. Most of all, I’m grateful to my lab. Their enthusiasm despite major roadblocks is a daily joy.”

Read more here: https://www.mcb.harvard.edu/uncategorized/doeke-hekstra-receives-nih-directors-new-innovator-award/