We are developing novel proteins, protein cages, and nanomachines using AI-driven approaches for targeted therapeutic, imaging and diagnostic applications, including drug delivery and cancer treatment.
We are developing novel imaging scaffolds to study the structure of small proteins with single particle cryo-electron microscopy (cryo-EM) and tomography (cryo-ET).
We use high-resolution techniques like cryo-electron microscopy (cryo-EM) to uncover the intricate 3D structures of proteins and viral components, offering critical insights into their fundamental mechanisms, such as virus maturation and cell communication.
Building on these structural insights, we design novel nanomaterials—such as virus-like particles—engineered with precise properties like stability, targeting ability, and cargo delivery.
Our dual goal is to deepen our understanding of these molecular structures while developing cutting-edge nanomedicines, including precision drug delivery systems and novel cancer therapies.
Learn more!
Discover more about our research by watching the talk "Engineered Protein Cages for Imaging Small Proteins by Cryo-EM" presented during the NIH CryoEM Current Practices Webinar.
References:
1- A suite of designed protein cages using machine learning algorithms and protein fragment-based protocols.
Meador, K.*, Castells-Graells, R.*, Aguirre, R., Sawaya, M.R., Arbing, M.A., Sherman, T., Senarathne, C., Yeates, T.O.
Structure (2024)
2- Design of a symmetry-broken tetrahedral protein cage by a method of internal steric occlusion.
Gladkov, N., Scott, E.A., Meador, K., Lee, E.J., Laganowsky, A.D., Yeates, T.O.#, Castells-Graells, R.#
Protein Science (2024)
3- Cryo-EM structure determination of small therapeutic protein targets at 3 Å resolution using a rigid imaging scaffold.
Castells-Graells, R., Meador, K., Arbing, M.A., Sawaya, M.R., Gee, M., Cascio, D., Gleave, E., Debreczeni, J.É., Breed, J., Leopold, K., Patel, A., Jahagirdar, D., Lyons, B., Subramaniam, S., Phillips, C., Yeates, T.O.
Proceedings of the National Academy of Sciences (2023)
4- Unravelling the Maturation Pathway of a Eukaryotic Virus through Cryo-EM.
Castells-Graells, R.#, Hesketh, E.L., Matsui, T., Johnson, J.E., Ranson, N.A., Lawson, D.M., Lomonossoff, G.P.#
BioRxiv (2024)