Compartmentalization of catalytic processes is a key feature that nature employs for maintaining temporospatial control over biological processes. Organs, tissues and cells are all examples of biological compartments. On an even smaller scale, intracellular organelles are the most important compartments in which catalytic processes take place. In the confined spaces of these organelles, the specific microenvironment maintains optimal enzyme function. More importantly, whole enzyme cascades can be organized within one organelle, enabling efficient tunneling of intermediates from one enzyme to the next and preventing toxic effects of intermediates.
In order to forward our understanding of the role of confinement in enzyme function, artificial organelles can be employed. Although most native organelles are encapsulated by a lipid-based membrane, protein nanocages have great potential for the development of artificial organelles. Especially viral capsids, such as that of cowpea chlorotic mottle virus (CCMV), are interesting candidates for development into artificial organelle shells. That is, the robust CCMV capsid is biocompatible and forms nanostructures with well-defined sizes and shapes. Even more intriguing, multiple approaches have been developed for the encapsulation of enzymes in viral capsids, resulting in uniform protein nanocage-based nanoreactors. These are exceptionally well-suited for development into artificial organelles.
The aim of my research project is to further our knowledge on the role of confinement in biology by creating artificial organelles based on protein nanocages and transient or permanent introduction of these catalytic compartments into hybrid cells. This may not only contribute to a better understanding of how confinement contributes to enzyme function, but additionally it may open up opportunities for the introduction of new functionalities to cells.
Protein-based artificial organelles are very promising tools for expansion of cellular function
Suzanne Timmermans (Geleen, 1993) received her M.Sc. in molecular life sciences from Radboud University in 2016. During her studies she worked on human mesenchymal stem cell culture in 3D hydrogels in the Physical Organic Chemistry group of Prof. Wilhelm Huck (Radboud University), in situ activatable cell-penetrating peptides in the Bio-Organic Chemistry group of Prof. Jan van Hest (Radboud University) and on a glycosyltransferase with expanded sugar substrate specificity in the group of Prof. Carolyn Bertozzi (Stanford University). As of March 2017, she is a Ph.D. candidate working on protein nanocage-based artificial organelles in the group of Prof. Jan van Hest.
Cargo-loading of hybrid cowpea chlorotic mottle virus capsids via a co-expression approachVirology (2022)
The Dynamics of Viruslike Capsid Assembly and DisassemblyJournal of the American Chemical Society (2022)
Artificial organelles based on hybrid protein nanoparticles(2022)
Sialic acid O -acetylationJournal of Biological Chemistry (2021)
Artificial OrganellesChemBioChem (2021)
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