| Project Detail |
Zooming in on protein structures could significantly expand treatment opportunities for dysfunction
Proteins including antibodies, enzymes and hormones are large, complex molecules required for most cell functions. Not surprisingly, protein dysfunction is at the root of numerous diseases and conditions. A characteristic mechanism of protein activity is binding with other molecules at specific sites via conformational changes. Precise characterisation of the detailed 3D structure underlying specific functions is critical to advancing understanding. Nobel-winning cryo-electron microscopy enables imaging of frozen hydrated specimens in their native state without dyes or fixatives. It has opened a new window on fine cellular structures at molecular resolution. IMpaCT is using this revolutionary technique to visualise proteins related to human health while raising the visibility of the coordinating university.
Objective
Proteins are building blocks of life, often forming complexes with essential cellular roles. Dysfunction of proteins or their complexes in cells are associated with a wide variety of pathologies, making them excellent drug target candidates. Their 3D structures are essential for a rational drug design. However, many important proteins and complexes are extremely hard to crystallize. Recent advances in Cryo-Electron Microscopy methodologies enabled the structure determination of large macromolecular complexes at near-atomic resolution. An unprecedented level of detail in cell imaging using Cryo-Electron Tomography is also now possible. IMpaCT will improve the expertise at the UNL in Cryo-EM methodologies applied to the structural studies of proteins related to human health (e.g. cancer, antiviral infections) from individual molecules to macromolecular complexes, both isolated and in a cellular context. To this end, UNL will team up with renowned Cryo-EM experts from the National Centre for Biotechnology of the Spanish National Research Council (Spain), the Institute of Biotechnology of the University of Helsinki (Finland) and the Weizmann Institute of Science (Israel). A solid work programme grounded on hands-on Workshops will be complemented with short-term visits to the partner labs, visits from partner labs experts to ITQB NOVA, seminars by leading experts in Cryo-EM (e.g. Nobel Prize winners), industry stakeholders’ engagement via a Mini-symposium and workshop participation, knowledge transfer to other research groups in Portugal and a WP devoted to early-stage researchers. An ambitious Dissemination, Exploitation and Communication plan will be implemented to leverage the research results potentiated by this project as high-impact publications and invited communications at international meetings, leading to a fundamental outcome: an increased visibility and activity of UNL researchers as players in the Cryo-EM field. |
