Designed DNA/Lipids – Poland

Centre for Programmable Biological Matter

FNP TEAM Project “Merging Programmable DNA Nanorobots and Microfluidics for Orientationally Controlled Delivery of Membrane Proteins to Protocells” (POIR.04.04.00-00-3CC0/16-00)

Total Award: 5,859,716 PLN, 100 % contribution from the European Regional Development Fund.

In our FNP-funded “TEAM” project we are using DNA as a building material to design and build novel nanostructures that will be able to interact with proteins in programmable ways. Find out more about FNP TEAM funding below. On this page we will keep you updated on out TEAM members, publications and other news.

Our project is in an area we refer to as “bionanoscience” – using biological molecules to build new, functional structures. This FNP (EU funding) research has allowed us to design hybrid DNA-lipid-protein structures aimed at controlling membrane proteins – a form of molecular robotics. Our extension to the grant has pushed us to extend our techniques further to develop new vaccine technologies.

Effect of the project: As well as the publications listed below, we hope that the project will lead to a new capabilities in bionanoscience and nanorobotics and, hopefully, lead long term to useful applications in therapeutics.

There has also been some unexpected benefits and synergy from our work- our expertise in handling lipids using lipid nanodiscs led to a successful collaboration with Konstantinos Beis at Imperial College culminating in our recent Science Advances paper reporting the structure of SbmA transporter protein.

FNP TEAM funding (FNP website)

Publications

Ghilarov, Dmitry, Satomi Inaba-Inoue, Piotr Stepien, Feng Qu, Elizabeth Michalczyk, Zuzanna Pakosz, Norimichi Nomura et al. “Molecular mechanism of SbmA, a promiscuous transporter exploited by antimicrobial peptides.” Science advances 7, no. 37 (2021): eabj5363. The cryo-EM structure of an interesting peptide transporter.

Islam, Md Sirajul, Gerrit David Wilkens, Karol Wolski, Szczepan Zapotoczny, and Jonathan Gardiner Heddle. “Chiral 3D DNA origami structures for ordered heterologous arrays.” Nanoscale Advances 3, no. 16 (2021): 4685-4691.Here we produced 3D “snub cube” DNA origami structures which were chiral – we could produce left-handed or right-handed forms.

Kumar, Mantu, Joanna Markiewicz-Mizera, Julian David Janna Olmos, Piotr Wilk, Przemysław Grudnik, Artur P. Biela, Małgorzata Jemioła-Rzemińska, Andrzej Górecki, Soumyananda Chakraborti, and Jonathan G. Heddle. “A single residue can modulate nanocage assembly in salt dependent ferritin.” Nanoscale 13, no. 27 (2021): 11932-11942.Here we showed how teh assembly and disassembly of ferritin can be modulated.

Shiu, Simon Chi-Chin, Yusuke Sakai, Julian A. Tanner, and Jonathan G. Heddle. “FRET-Mediated Observation of Protein-Triggered Conformational Changes in DNA Nanostructures.” In Polypeptide Materials, pp. 69-80. Humana, New York, NY, 2021.Detailed method of how we used FRET to observe opening and closing of a DNA nanorobot.

Chakraborti, Soumyananda, Antti Korpi, Jonathan G. Heddle, and Mauri A. Kostiainen. “Electrostatic Self-Assembly of Protein Cage Arrays.” In Polypeptide Materials, pp. 123-133. Humana, New York, NY, 2021 A detailed method of how we arrayed ferritin with active cargo.

Chakraborti, Soumyananda, Antti Korpi, Mantu Kumar, Piotr Stepien, Mauri A. Kostiainen, and Jonathan G. Heddle. “Three-dimensional protein cage array capable of active enzyme capture and artificial chaperone activity.” Nano letters 19, no. 6 (2019): 3918-3924 AS part of our efforts to deelop protein-DNA interactiosn we developed protein cages which are able to array active cargo in regular lattices.

Balakrishnan, Dhanasekaran, Gerrit D. Wilkens, and Jonathan G. Heddle. “Delivering DNA origami to cells.” Nanomedicine 14, no. 7 (2019): 911-925. A review covering the potential and challenges of using DNA origami a a cell-delivery vehicle

Sakai, Y., Islam, M. S., Adamiak, M., Shiu, S.C.-C., Tanner, J. A., Heddle, J. G., (2018) DNA Aptamers for the Functionalisation of DNA Origami Nanostructures, Genes 9, pp. 571 [MDPI]A summary of how DNA aptamers have been used alongside DNA origami.

Shiu, S.C.-C., Kinghorn, A.B., Sakai, Y., Cheung, Y-W., Heddle, J.G., Tanner, J.A. (2018) The Three S’s for Aptamer‐Mediated Control of DNA Nanostructure Dynamics: Shape, Self‐Complementarity, and Spatial Flexibility, ChemBioChem 19, pp. 1900-1906 [Wiley]A guide for designing aptamers to work with DNA origami.

Tang, M. S., Shiu, S. C-C., Godonoga, M., Cheung, Y-W., Liang, S., Dirkzwager, R. M., Kinghorn, A. B., Fraser, L. A., Heddle, J. G.*, Tanner, J. A.* (2018) An aptamer-enabled DNA nanobox for protein sensing, Nanomedicine 14(4), pp. 1161-1168 [Elsevier]
We show that the opening and closing of a DNA origami box can be controlled by molecular locks that respond to a malarial diagnostic signal.