AI-Designed Proteins: New Antifreeze for Organ Preservation | TU/e
- The challenge of preserving organs for transplant is a race against time.
- Currently, about 104,000 people in the United States are on the waiting list for a transplant, with nearly 60,000 considered immediately eligible due to the severity of their...
- The core problem lies in the formation of ice crystals within organ tissues during cooling and storage.
The challenge of preserving organs for transplant is a race against time. Every hour counts when it comes to maintaining the viability of a heart, lung, or kidney removed from a donor. Now, researchers are making strides in extending that window, inspired by the natural antifreeze mechanisms found in Arctic fish. A new generation of artificially designed proteins promises to revolutionize organ preservation, potentially saving thousands of lives currently lost while waiting for a transplant.
Currently, about 104,000 people in the United States are on the waiting list for a transplant, with nearly 60,000 considered immediately eligible due to the severity of their condition. While saw a record number of liver, heart, and lung transplants, the demand still far outweighs the supply. Tragically, approximately 6,000 eligible patients die each year – that’s 17 people each day – while awaiting a life-saving organ. Even small delays in transport or preservation can prove fatal.
Mimicking Nature’s Ice Protection
The core problem lies in the formation of ice crystals within organ tissues during cooling and storage. These crystals physically damage cells, disrupting vital structures and rendering the organ unusable. Researchers have long been fascinated by “antifreeze proteins” (AFPs) found in certain fish that inhabit frigid waters. These proteins bind to ice crystals, preventing their growth and protecting the fish from freezing solid.
A team at the Technical University of Eindhoven (TU/e) in the Netherlands, led by researcher Voets, is taking a novel approach to harnessing the power of AFPs. Rather than relying on isolating these proteins from ice fish – a process that is both ecologically sensitive and limiting – they are using bacteria to produce them. “In the chemical biology laboratory at TU/e, we use bacteria to produce ice-binding proteins for us,” Voets explained. “This way, we don’t have to isolate them from ice fish for our research. That’s not only better for the ice fish, but also useful for us, because it allows us to tinker with the protein structure very precisely in order to find out which parts are essential for the function of the proteins.”
AI-Designed Proteins with Enhanced Stability
The TU/e team didn’t stop at simply replicating existing AFPs. Collaborating with researchers at Wageningen University &. Research and Washington University, they employed artificial intelligence to design entirely new proteins with improved ice-binding properties. These artificial proteins are then produced using E. Coli bacteria. The result, as detailed in a recent paper published in PNAS, is a new family of proteins that are more stable, more active, and more versatile than naturally occurring AFPs.
“Naturally occurring ice-binding proteins are generally only found in cold environments,” Voets noted. “Some of these proteins already lose their characteristic folding and thus their ability to bind ice at room temperature. The new class of proteins we developed remains stable in a much wider temperature range.” This enhanced stability is a crucial advantage for practical applications, particularly in organ preservation. The ability to add these proteins to organs without the need for constant, extremely low-temperature storage simplifies handling and reduces logistical challenges.
A Converging Set of Technologies
This breakthrough isn’t solely a result of innovative protein engineering. Voets emphasizes that it’s a convergence of several key technological advancements. Progress in computational methods for protein design, coupled with the availability of powerful super-resolved fluorescence microscopes at the ICMS Advanced Microscopy Facility, has allowed researchers to track the interaction of these proteins with ice crystals at an unprecedented level of detail. Interdisciplinary collaborations with biomedical engineers, cardiologists, and transplant surgeons have been essential to translating these findings into potential clinical applications.
From Lab to Practical Application
Beyond the proteins themselves, researchers are exploring ways to incorporate these ice-binding properties into more scalable and cost-effective materials. TU/e researcher Tim Hogervorst discovered that the essential properties of these proteins can be transferred to polymer-based materials, opening the door to wider production. In collaboration with The Gate, a regional innovation hub, Voets and Hogervorst are working to transform this discovery into a tangible product.
A Proof of Concept grant of €150,000 from the European Research Council will further support this effort. This funding will be instrumental in bridging the gap between laboratory research and real-world application, ultimately aiming to improve the preservation of tissues and organs for transplant. Current organ preservation methods, such as the Celsior solution – initially developed for heart preservation – are effective, but the potential of these new, bio-inspired proteins offers a promising avenue for extending organ viability and increasing the number of successful transplants.
While still in the early stages of development, this research represents a significant step forward in addressing the critical shortage of organs available for transplant. By extending the window of opportunity for organ preservation, scientists are working to give more patients a second chance at life.