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Ronit Freeman uses nature’s building blocks to create innovative technologies, from synthetic cells to treatments that could transform health care.

Ronit Freeman in a lab
Ronit Freeman and her lab of chemists, engineers, and biologists work together to innovate next-generation health solutions using biological materials. (photo by Alyssa LaFaro)

 

“Let me show you an example.”

Ronit Freeman stops mid-interview to have her research operations manager, Ana Sanchez, wheel a small table into her office. Sitting on top of it is a bowl of water, into which Sanchez promptly dumps a cupful of cut-up green drinking straws. Freeman dips her finger in and swirls the water around and around.

“Watch what happens,” she instructed, excitedly.

Surprisingly, the straws begin to interact. They stick together, sometimes end-to-end and other times side-to-side. The more Freeman stirs the water in the bowl, the more they seem to attract to one another.

“And if we added more straws to the bowl, increasing the density, they will actually make different patterns than you’re seeing here,” she explained. “The shape of the straws and the tension of the water are why they want to connect in different ways.”

This process is called self-assembly, when a local interaction causes a disordered system to transform into an organized structure. Freeman uses this design principle to build innovative technologies. As a professor of applied physical sciences at UNC-Chapel Hill, she specializes in combining and molding biological components into functional materials where the whole is greater than the sum of its parts.

“The inspiration is anything that nature can do, and the medium is any biological material that exists in nature,” she explained. “We can design and chemically modify peptides, DNA, nucleic acids, sugars, lipids — any architectural building block that is biological. It’s a chemical approach to materials design.”

From synthetic cells to a rapid test for respiratory infections, Freeman has generated a pipeline of groundbreaking technologies that address global challenges in health care by emulating how cells build, signal and manufacture needed components.

“My company is my lab,” she said. “We do everything from the molecular design of a chemical to the validation and application of it. We produce assets and then find an established partner who has the manufacturing, distribution, and pharmacy pipeline to get it to the market.”

Creating cell factories

In her early research, Freeman uncovered how to link peptides together by using DNA like a molecular glue. With this technique, she achieved multiple scientific “firsts,” from creating a synthetic collagen, the molecule that makes up our skin to, most recently, generating synthetic cells that can serve specific functions — like delivering drugs directly to infected cells and making plastics that eventually biodegrade.

“We want to make materials for tasks, not to last,” she said. “We want those materials to serve a task, degrade and disappear.”

Most cell function and flexibility comes from its cytoskeleton, which provides a framework for the cell — much like the frame of a house. Freeman’s synthetic cells have functional cytoskeletons that can change shape and react to their surroundings.

The goal of this research is to make “little factories” that can imitate living cells to produce molecules like insulins.

“One of the things we’re trying to do is combine the synthetic cells with living cells and program them to make certain molecules on demand that would then be released as therapeutics in the body,” Freeman said.

These cells can also be programmed to create products cells don’t normally produce, like polymers, with the potential to replace big chemical factories.

“It would mean a future with much less waste and a much smaller footprint,” Freeman said. “That’s the idea.”

Unraveling disease

Freeman is also using the concept of self-assembly to unpack how chirality — the direction in which a molecule twists — affects disease progression in the brain and the lungs.

Many neurodegenerative diseases, like Alzheimer’s and Parkinson’s, have been associated with malfunctioning proteins that stick together to form amyloids, which can disrupt cell function and cause cognitive decline. The molecules that make up these plaques twist to the left and fail to break down because enzymes can only degrade materials that spiral right.

“We thought that if we could make the amyloids twist the other way, maybe the enzymes would break them down,” Freeman said.

Her team simulated this phenomenon in the lab using the same peptides found in brain amyloids. By applying heat, they could force the plaques to twist in the opposite direction — an instrumental discovery they documented in a recent Nature Communications paper. Now, they are experimenting with human spinal fluid samples to determine if they can use targeted ultrasound beams to reverse the twist of these protein deposits in the brain.

Freeman’s innovative approach to protein manipulation has multiple applications. In partnership with Carolina pulmonologist James Hagood, she is using synthetic peptides to break down scar tissue in the lungs.

Pulmonary fibrosis is a chronic disease that damages lung tissue via excess collagen and protein deposits that block the airway. Up to 40,000 Americans die from the disease each year, and the life expectancy after diagnosis is just three to five years. North Carolina has one of the highest mortality rates in the U.S.

The disease’s progression has been associated with decreased production of a particular protein. In response, Freeman created a synthetic peptide to mimic the protein’s structure. When applied to fibrotic animal models and human lung tissues, the peptide therapy eliminated the fibrosis.

“It’s like magic. You see a highly fibrotic lung — and poof!” exclaimed Freeman, waving her hands across the air. “After treatment with our peptide, it comes back looking like normal.

“We are very excited to move this project into clinical trials soon,” she added. “There is currently no cure and the only two FDA-approved treatments just delay the symptoms and don’t resolve the disease. The potential impact of a drug like ours in the market would be absolutely transformative.”

Solving global health challenges

Peptides aren’t the only tool Freeman uses to create her technologies. Any biological material is fair game — even sugar.

In 2020, Freeman created GlycoGrip, a rapid test to detect COVID-19. When Freeman began thinking about how to design an efficient test, she considered how viruses work: They reproduce via host cells. And all cells have branch-like sugars on their surfaces that act as a gateway for letting molecules in and out.

Freeman compares these sugars to lint brushes because they capture and bind certain molecules. Could she mimic that cellular process in a test by using sugars to capture viruses? Turns out, she can.

GlycoGrip will hit the market soon. Freeman’s latest evolution of the test can identify multiple upper respiratory viruses at once, including COVID, the flu, and RSV.

“If you just have a sniffle or chills, you could have any number of viruses,” Freeman said. “Right now, you must go to a clinic to run a panel on every single virus you want to test for — and that’s expensive. The goal is one swab that tests for everything.”

Breaking barriers

When Freeman joined Carolina in 2018, it was her first faculty position. Most new professors start with an “assistant” title, but she was hired as an associate professor. Her research had already been featured in over 40 publications, and her highly interdisciplinary training — including time spent as an officer in the Israeli Army leading teams of over 100 people — gave her more experience than a typical new professor.

The lab she’s built includes members from all over the world who specialize in everything from chemistry to engineering to biology and medicine.

“I don’t only think about the diversity of people but diversity of ideas, of molecules, of concepts and how they come together to create something new,” she said. “Lines between disciplines have to blur, and barriers have to come down for innovation to happen.”

And in the end, she credits the importance of family support to her achievements.

“Every morning when I drive in, I speak with my mother back in Israel, who’s continuously fueled my success ever since I was a child,” she said. “And then, when I step out of my lab coat each day and walk into my home in Chapel Hill, I am engulfed with a blanket of love and encouragement from my husband and children, enabling me to do what I do.”

Ronit Freeman is an associate professor in the Department of Applied Physical Sciences within the UNC-Chapel Hill College of Arts and Sciences.

By Alyssa LaFaro, UNC Research

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