Modular DNA Nanocompartments for Programmable Biomolecular Transport

• Applicant: Professorin Dr. Barbara Saccà
• Subject Area: Biological and Biomimetic Chemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562785419

Biological compartmentalization significantly enhances biochemical processes by managing spatial organization and exploiting nanoscale effects, such as increased reactant concentration and stochastic dynamics. While recent advancements in DNA nanotechnology have enabled the creation of artificial nanocompartments capable of housing proteins and enzymes, critical questions regarding the control of cargo transport, protein orientation, and reaction acceleration remain unanswered. This project seeks to tackle these issues by employing the motor protein p97 as a model system to investigate the interactions and efficiencies of molecular motors within these engineered nanocompartments. Building on prior research involving a two-compartment DNA chimera designed for protein unfolding and degradation (utilizing p97 and alpha-chymotrypsin), we aim to refine these compartments for precise cargo transport and reaction sequencing, ensuring that biochemical processes are conducted in a controlled and efficient manner. A central focus of the project is to elucidate the factors that dictate and stabilize the orientation of the motor protein within the compartment, which is crucial for its functionality. Furthermore, we propose an innovative approach to monitor the dynamics of the motor at the single-molecule level, yielding valuable insights into its performance across various environments. By addressing these challenges, we aim to enhance our understanding of nanoscale confinement and its influence on biochemical processes while developing advanced tools for studying and engineering biochemical reactions. These innovations hold the potential to facilitate the creation of novel biocatalytic cascades and to provide critical insights into energy conversion at the nanoscale.

• DFG Programme: Research Grants