S-layers are two-dimensional crystalline lattices that coat microbial cells, providing protection and structural integrity. Using cryo-electron microscopy, investigated various archaeal and bacterial S-layers. Focusing on the S-layer of the archaeon Sulfolobus acidocaldarius, we determined its structure at high resolution and built an atomic model. Informed by this model, we introduced affinity tags into exposed glycan sites, enabling functionalisation with various ligands, and determined a chemical switch to trigger in vitro assembly and disassembly. This gave rise to "smart", pH-sensing nanocapsules for novel drug delivery solutions.
In parallel, we resolved the structures of six archaeal surface filaments: three archaella, two type IV pili, and a newly discovered filament we named the "thread." Archaella function as rotary nanomotors for swimming motility. By developing new cryoEM image processing tools, we advanced our understanding of these archaella and challenged prior models of their composition and dynamics, informing the development of bioinspired nanoproellers for microrobotics.
Among pili, we focused on the Aap filament, involved in twitching motility. Our data showed that Aap adopt a metastable triple-helix structure that spontaneously retract without energy input, which provide useful tools for microrobotic systems requiring autonomous actuation.
The thread filament is exceptionally stable, resistant to acid, heat, detergents, and enzymatic degradation. It assembles into cable-like bundles and features a linear chain of aromatic residues arranged in a geometry compatible with electron tunnelling. This makes the thread an attractive candidate for biodegradable nanowires usable in sustainable bioelectronics.
We disseminated our findings through open-access journals, preprints, media outreach, and public engagement events. Our research was widely presented by an eminent science YouTuber, reaching over 94,000 viewers. We also engaged with pharmaceutical companies to explore the translational potential of our encapsulation technology. Finally, our project enabled our co-creation and participation in a new Marie Skłodowska-Curie Doctoral Network called ArcTech, to train early-career researchers in archaeal biology and biotechnology.
