Protein sensing and actuation using DNA-based molecular circuits

DNA has emerged as a highly versatile construction material for nanometer-sized structures and sophisticated molecular machines and circuits. The successful application of nucleic acid based systems greatly relies on their ability to autonomously sense and act on their environment, however. In close collaboration with other ICMS research groups (de Greef, Prins, Tel), we develop generic strategies for DNA-based control of protein activity and the application of DNA-based molecular computing to construct autonomous biomolecular systems with sophisticated signal integration, processing and actuation properties. We introduced bivalent peptide-dsDNA ligands as effective, non-covalent and reversible antibody blockers that allow control of antibody activity using a variety of triggers including protease activity, oligonucleotides and aptamers. We also developed Antibody Templated Strand Exchange (ATSE) as a generic method to translate the presence of an antibody into a unique DNA strand, enabling the use of antibodies as specific inputs for DNA-based molecular computing.

Key wordsDNA nanotechnology, DNA computing,  antibody actuation, antibody detection, protein-DNA hybrids

Key publications

  • Engelen, W., Meijer, L.H.H., Somers, B., de Greef, T.F.A. & Merkx, M. (2017). Antibody-controlled actuation of DNA-based molecular circuits. Nature Communications,
  • Engelen, W., Janssen, B.M.G. & Merkx, M. (2016). DNA-based control of protein activity. Chemical Communications, 52(18), 3598-3610.
  • Janssen, B.M.G., Rosmalen, van, M., van Beek, L. & Merkx, M. (2015). Antibody activation using DNA-based logic gates. Angewandte Chemie - International Edition, 127(8), 2560-2563
  • Janssen, B.M.G., Engelen, W. & Merkx, M. (2015). DNA-directed control of enzyme-inhibitor complex formation: a modular approach to reversibly switch enzyme activity. ACS Synthetic Biology, 4(5), 547-553.

Working on this topic