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The Buck Institute and Georgetown University are co-leading SEEDS, a four-year research effort backed by an Advanced Research Projects Agency for Health award of up to $51.7 million. The team plans to combine artificial intelligence with experiments to predict how intrinsically disordered proteins change under different cellular conditions, initially studying Alzheimer’s disease and Ewing sarcoma. The award supports research; it does not establish that the approach can yet prevent disease or produce new treatments.
The Advanced Research Projects Agency for Health has awarded up to $51.7 million to a four-year consortium co-led by the Buck Institute for Research on Aging and Georgetown University to study how flexible proteins begin shifting toward disease-associated states. The project, called SEEDS, will combine artificial intelligence and laboratory experiments, with an initial focus on Alzheimer’s disease and Ewing sarcoma.
SEEDS stands for Sequence-to-disease: Environment-aware Ensembles of Disordered proteins at Scale. The consortium aims to predict how a protein’s sequence and the conditions around it affect its behavior, and to identify changes that may precede harmful misfolding or clumping. The award is for research intended to support future detection and treatment strategies; the source report does not describe a diagnostic or therapy already developed.
The work centers on intrinsically disordered proteins, or IDPs. Unlike proteins that tend to settle into a relatively stable three-dimensional structure, IDPs can take on multiple shapes. Factors inside cells—including acidity, molecular crowding, metals, metabolites and chemical modifications—can influence those forms. That flexibility is part of how the proteins function, but it also makes their behavior difficult to predict and their disease-associated forms challenging to target.
Georgetown’s Priyanka Joshi, PhD, and the Buck Institute’s Chuankai (Kai) Zhou, PhD, co-lead the effort. The consortium includes researchers from nine academic institutions and seven industry partners, drawing on expertise in protein science, AI, computational modeling, cancer and neuroscience. Its approach will test computational predictions against experiments under different conditions, rather than relying on models alone.
Why Early Protein Changes Matter
Many proteins linked to neurodegenerative disease and some cancers are difficult to target with conventional drug-development methods because they lack the stable shapes and binding pockets that many medicines are designed to fit. Better ways to describe how these proteins behave in changing cellular environments could help researchers identify states that current structural snapshots miss.
The project’s potential value is earlier detection: researchers want to recognize shifts toward harmful behavior before proteins aggregate and damage cells. If the predictions prove reliable, they could inform future diagnostic research and efforts to redirect protein behavior. Those are goals of the project, not outcomes demonstrated by the award announcement.
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From Protein Snapshots to Prediction
Researchers can capture information about proteins, but the source report says that for disordered proteins, observations often come after they have clumped together. Scientists cannot yet reliably predict how these proteins will behave as conditions inside a cell change, or exactly when a change becomes harmful. The resulting gap complicates efforts to understand early disease processes.
AI systems such as AlphaFold have advanced protein science by learning from extensive accumulated structural data. Zhou said there is not a comparable depth of structural information for intrinsically disordered proteins, making their behavior harder to model. SEEDS aims to help address that gap by gathering data at scale and pairing physics-guided AI with experiments that can refine its predictions.
The consortium brings together Georgetown’s INTREPID and the Buck Institute’s SHIFT teams as part of ARPA-H’s BIOmolecular Grammar for protein Aggregation Modulation and Intervention, or BIOGAMI, program. BIOGAMI focuses on early protein dysfunction, before misfolding or aggregation causes lasting cellular damage. ARPA-H Program Manager Shannon Greene leads the program.
“We aim to uncover the principles that determine when these proteins remain in healthy functional ensembles and when they begin to shift toward disease-associated states.”
— Chuankai (Kai) Zhou, assistant professor at the Buck Institute
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What the Award Cannot Yet Show
The announcement does not report a validated tool that can predict disease in people, nor does it provide results showing that SEEDS has detected or reversed harmful protein changes. It is also not clear from the source report how the award’s “up to” amount will be distributed, which specific proteins will be studied first, or what performance measures the team will use to judge its predictions.
The proposed approach must be tested experimentally, and its usefulness for diagnostics or treatment remains uncertain. The initial focus on Alzheimer’s disease and Ewing sarcoma does not mean that the work has already produced findings applicable to either condition, or that it will lead to a clinical intervention.
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Research Moves Into Testing
Over the four-year award period, the team plans to collect and analyze data on protein behavior across different conditions, build predictive models and compare those predictions with experimental measurements. That cycle of modeling and testing is intended to improve understanding of how sequence and cellular surroundings relate to protein behavior.
The next meaningful milestones will be evidence that the models can predict experimental results and that the identified changes are relevant to disease processes. The source report does not give a schedule for interim findings, clinical studies or product development. For now, the award marks the start of a research program rather than a change in available patient care.
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Key Questions
What is the SEEDS project?
SEEDS is a four-year research consortium co-led by the Buck Institute and Georgetown University. It aims to predict how intrinsically disordered proteins behave as their sequence and cellular environment interact.
How much funding did the project receive?
The Advanced Research Projects Agency for Health awarded the effort up to $51.7 million. The source report does not provide a breakdown of the funding.
Which diseases will the team study first?
The project’s initial focus is Alzheimer’s disease and Ewing sarcoma. The announcement does not report disease-specific findings from the team.
Does this mean a new diagnostic or treatment is available?
No. The award funds research intended to support future diagnostic and treatment approaches. The report does not describe a validated diagnostic, treatment or clinical result from SEEDS.
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