Healthcare (Commonwealth Union) – Ahmet F. Coskun and his research team are advancing their ambitious project to build a 3D atlas of the human body, mapping cells and tissues in detail. Along the way, they’re uncovering insights that could pave the way for improved treatments for the most common form of lung cancer.
In the process, they are breaking new ground in scientific exploration and potentially laying the foundation for a new commercial enterprise.
In 2023, Coskun’s group introduced a groundbreaking study in “single-cell spatial metabolomics,” with the focus on the distribution of small molecules—metabolites—within tissues and organs. Now, they are leading efforts in “spatial interactomics,” a field dedicated to studying interactions between various biomolecules within individual cells.
To better understand these interactions, they have developed a cutting-edge tool called the “intelligent sequential proximity ligation assay,” or iseqPLA, designed to explore why non-small cell lung cancer (NSCLC) resists treatment in so many patients.
Coskun, Bernie Marcus Early Career Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University indicated that it is a smart assay that allows them to observe proteins and their spatial interactions.
“Basically, we’re the first to create a new research area on spatial protein-protein interactions, which can tell us more about cell types and their functions,” explained Coskun. “With spatial interactomics, we can validate how cells physically touch, sense, and regulate nearby cells through the interaction of pairs of proteins.”
The primary aim of spatial interactomics is to uncover how protein-protein interactions contribute to drug resistance in NSCLC. The iseqPLA technique offers scientists a window into these dynamics, visualizing them at the subcellular level. Coskun’s team recently published their findings in Nature Biomedical Engineering and is working on launching a company to bring this innovative technology to market.
Tyrosine kinase inhibitors (TKIs), such as Osimertinib, have revolutionized NSCLC treatment, offering significant benefits to many patients. However, a common challenge remains: resistance often develops over time, diminishing the drugs’ effectiveness. Researchers believe that protein interactions—molecular exchanges akin to cellular “conversations”—play a pivotal role in this resistance.
Proteins are constantly interacting, governing critical cellular processes like growth, division, and survival. Coskun’s team is focused on mapping how these interactions evolve during cancer treatment. Using iseqPLA, they can “tag” proteins with fluorescent markers, revealing their locations and interactions in real-time under a microscope. This breakthrough could pave the way for more effective cancer therapies.
Coskun described it as a highly detailed map revealing how various proteins in a cell are interconnected.
The iseqPLA method can analyze 47 protein interactions within a single sample, significantly reducing the time and resources required compared to traditional methods, which typically examine only two to three interactions at a time.
Additionally, the researchers developed a computer model to interpret the spatial data gathered by iseqPLA. This model identifies patterns in protein interactions, aiding in predictions about whether a cell is responding to treatment or developing resistance.
“We showed that the test works not only in lab-grown cells but also in tissues from mice and humans,” added Coskun. “It can really help us understand how patients respond to certain treatments.”
Looking ahead, Coskun intends to refine iseqPLA to explore the interplay between RNA, proteins, metabolites, and other subcellular dynamics. Additionally, he aims to make the technology accessible to other researchers.
He indicated that they believe that it will be a revolutionary tool.
With this vision, Coskun is in the process of launching a startup called SpatAllize. He is collaborating with VentureLab, a nonprofit at Georgia Tech that supports entrepreneurial initiatives for students and faculty.
He further pointed out that they are currently conducting customer interviews and developing a strategic plan to bring the technology to market.
