Engineered Affimers for cryo-EM studies of unsolved protein structures
Lead Research Organisation:
University of Leeds
Department Name: Sch of Biology
Abstract
Cryogenic electron microscopy (cryo-EM) has revolutionised structural biology and has enabled us to see atomic structures of challenging macromolecular assemblies, including amyloid fibres, SARS-CoV-2 and protein structures in cells. However, challenges remain to determine structures of small proteins using cryo-EM routinely. Small proteins such as kinases are excellent targets for drug discovery. However, due to their small size, cryo-EM is not particularly useful to study structures of such proteins with ligands.
In this project, we will engineer non-antibody-binding proteins Affimers to develop a new toolkit and methodology that solves these challenges. Affimers are a Leeds-born technology and have been successfully used to visualise proteins and regulate their functions. We seek to extend the application of Affimers to cryo-EM. The project particularly focuses on developing an Affimer-based cryo-EM methodology, universally applicable to recombinant proteins.
As a model target protein, we will use a 40 kDa mitotic kinase Aurora-A, of which cryo-EM structure has been undetermined. Aurora-A is an essential regulator of mitosis and a compelling target for cancer drug discovery. Thus, the project will contribute to a major challenge in fundamental biology and human health.
In this project, we will engineer non-antibody-binding proteins Affimers to develop a new toolkit and methodology that solves these challenges. Affimers are a Leeds-born technology and have been successfully used to visualise proteins and regulate their functions. We seek to extend the application of Affimers to cryo-EM. The project particularly focuses on developing an Affimer-based cryo-EM methodology, universally applicable to recombinant proteins.
As a model target protein, we will use a 40 kDa mitotic kinase Aurora-A, of which cryo-EM structure has been undetermined. Aurora-A is an essential regulator of mitosis and a compelling target for cancer drug discovery. Thus, the project will contribute to a major challenge in fundamental biology and human health.
Organisations
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/T007222/1 | 01/10/2020 | 30/09/2028 | |||
2878046 | Studentship | BB/T007222/1 | 01/10/2023 | 30/09/2027 |