Welcome!

The unano consortium exists to advance bionanotechnology research in Europe, having been kick-started by funding from the Una Europa alliance. Unano runs a monthly webinar series about bionanostructures and bionanomachines, enabling researchers across the globe to give talks on their current endeavours in the field. Anyone can attend our webinars, and the joining link and webinar programme are provided below.

The unano webinar series is co-hosted by Dr Katherine Dunn’s research group at the University of Edinburgh and Prof Jonathan Heddle’s group at Durham University. Lucy Epton at Durham is in charge of devising the webinar schedule, and if you are interested in giving a talk for us please contact her by email at lucy.epton@durham.ac.uk. James Dodd at Edinburgh is in charge of maintaining the blog and running the webinar platform and can be reached by email at J.Dodd-3@sms.ed.ac.uk.

January 2025 marked the kick-off of the unano webinar series, which expands on the previous webinar series run by Katherine’s group on the narrower theme of DNA Nanotechnology. That series was chaired and organised by Dr Matthew Aquilina initially and later James Dodd; more details (including recordings of some sessions) can be found here.

Next webinar: 3pm (UK time), 30th April 2025

Join Here

Prior registration is not required. To join the webinar just click the link as (or shortly before) the webinar starts and type the name by which you wish to be known. If you join the webinar as a group please indicate this in your name, so we have some idea how big the audience is.

Webinar schedule

3pm, 29th January 2025:

James Dodd (University of Edinburgh): Title TBC

Greg Knight (Durham University): Title TBC

3pm, 26th February 2025:

Ho Yeung Chim (Ludwig-Maximilians-Universität München): Computational design of small molecule-dependent cyclic oligomers:

Designing protein oligomers that respond to small molecules is a significant challenge in dynamic protein assembly design and is crucial for interfacing with biological systems. I have introduced a new module within RFdiffusion for specifically designing cyclic oligomers by leveraging pre-existing interfaces. This design module focuses on the scaffolding of symmetrized target interfaces, ensuring that the properties of the interface are preserved in the final oligomer design. I computationally designed cyclic oligomers with varying symmetries derived from neomorphic PPIs, as a first step towards creating controllable and dynamic protein assemblies.

Göktuğ Aba (Leiden University Medical Centre): Inducing cancer cell killing using DNA nanostructure-mediated superclustering of death-receptors:

Clustering of type-II tumour necrosis factor receptors (TNFRs) is required to induce intracellular signaling. Current methods for receptor clustering lack precise control over ligand valency and spatial organization, potentially limiting optimal TNFR activation, biological insight, and therapeutic efficacy. DNA nanostructures provide nanometer-precise control over molecular arrangement, allowing control of both ligand spacing and valency. Here, we produce a DNA nanostructure decorated with controlled numbers of engineered single-chain TNF-related apoptosis-inducing ligand (sc-TRAIL) trimers. These trimers cluster death receptor 5 (DR5), enabling investigation of the geometric parameters influencing apoptotic pathway activation. We show that cell killing is affected by both valency and separation of sc-TRAIL trimers, which can be utilized to induce cell killing in human primary pancreatic and colorectal cancer organoids. Together, our data shows that precise control of receptor clustering through spacing and valency enhances our understanding of receptor activation mechanisms and informs the development of more effective cancer therapies.

3pm, 26th March 2025:

Mai P. Tran (Max Planck Institute):

Bottom-up synthetic biology seeks to engineer a cell from molecular building blocks. With DNA nanotechnology, several building blocks, such as cytoskeletons, have been reverse-engineered. However, because they currently rely on chemical synthesis and thermal annealing, synthetic cells cannot produce these DNA nanostructures from their constituents, like nucleotides. Here, we introduce RNA origami cytoskeleton mimics as an alternative set of nucleic acid-based molecular hardware for synthetic cells, which we express directly inside of GUVs containing a DNA template and a polymerse, chemically fuelled by feeding nucleotides from the outside. We designed RNA origami tiles which fold upon transcription and self-assemble into micrometer-long 3D RNA origami nanotubes at constant temperature. We find that sequence mutations on the DNA template lead to different phenotypes of RNA origami nanotubes, including the formation of closed rings. Molecular dynamics simulations and experiments show that these phenotypic transitions can be explained by alterations in the stability of RNA secondary structures and modifications to available assembly pathways. Additionally, we achieved RNA origami cortex formation and membrane deformation caused by RNA nanotube polymerization. Altogether, this work pioneers the expression of RNA origami-based hardware towards active, evolvable, and RNA-based synthetic cells.

Zuza Pakosz-Stepien (Durham University): Tailoring pH sensitive protein cages:

The rational design and creation of novel engineered protein cages are an important area of research in synthetic biology. Such cages can serve as versatile and adaptable platforms with significant applications in biomedicine. Precisely controlling the interactions between protein subunits is crucial, as it enables the controlled assembly and disassembly critical for applications such as drug delivery. Here, we present a new approach to assembling protein cages from identical protein building blocks. In previous work we were able to form protein cages with ring-shaped TRAP proteins linked via linearly coordinated gold(I) (1). Our new method utilizes TRAP with strategically positioned metal binding sites, each capable of coordinating metal ions with higher coordination numbers. These engineered proteins can self-assemble into highly stable cages in the presence of cobalt or zinc ions. Furthermore, the cages can be disassembled on demand through external triggers like chelating agents and pH changes. Interestingly, for certain triggers, the disassembly is reversible, allowing the cages to reassemble when triggering conditions cease. This work offers a promising platform for developing advanced drug delivery systems and other biomedical applications.

Malay, A.D., Miyazaki, N., Biela, A. et al. An ultra-stable gold-coordinated protein cage displaying reversible assembly. Nature 569, 438–442 (2019). https://doi.org/10.1038/s41586-019-1185-4

3pm, 30th April 2025:

Sara Garcia Linares (Complutense University of Madrid): Design of nanoreactors for microplastic depolymerization based on pore-forming toxins

Actinoporins, typically non-catalytic proteins, have been engineered into biocatalytic nanoreactors capable of breaking down PET plastics. The presentation covers their mechanism of action, efficiency compared to existing PETases, and future directions such as optimizing pore size, integrating multiple catalytic activities, and developing water-soluble or immobilized nanoreactors.

3pm, 28th May 2025:

Matthew Aquilina (Dana Farber Cancer Institute, Harvard University): Crisscross origami

Ranjan Sasmal (Arizona State University): Title TBC