51³Ô¹ÏÍø

A team of 51³Ô¹ÏÍø students is taking an unexpected biological building block, a non-pathogenic fungal prion and repurposing it to create a customisable protein hydrogel with potential applications in biotechnology, biosensing and biocatalysis.

The 2026 51³Ô¹ÏÍø iGEM team is developing a modular, self-assembling protein hydrogel based on HET-s, a fungal prion found in Podospora anserina. While amyloid structures are often associated with disease, HET-s is a functional protein that naturally assembles into highly ordered fibres and performs a biological role in the fungus.

The team, supported by Szymon Manka, aims to harness this natural self-assembly mechanism as the structural basis of a programmable protein hydrogel.

A scaffold that can be given different functions

The hydrogel is designed to form a stable protein network that can be easily functionalised with different proteins.

Rather than engineering a new scaffold for every application, the team is developing a plug-and-play system in which functional proteins can be incorporated and immobilised within the hydrogel without redesigning the entire material.

At the centre of this approach is Sortase A, an enzyme that acts as a molecular “stapler”. Sortase A recognises short peptide tags and forms a site-specific bond between them, allowing compatible enzymes, binding proteins or fluorescent reporters to be incorporated into the hydrogel using the same attachment strategy.

This means that the same underlying material could potentially be adapted for different purposes simply by changing the functional protein attached to it. The platform could therefore provide a flexible foundation for applications including biotechnology, biocatalysis, biosensing, and biomaterials and would enable reuse of the enzymes instead of repurifying them.

Making the material reversible

The team is also designing the hydrogel so that its structure can be controlled on demand.

The hydrogel network is crosslinked using streptavidin as a multivalent node protein. The scaffold is connected to these nodes through a weaker-binding biotin analogue. Adding free biotin, which binds more strongly to streptavidin, competitively displaces the analogue and releases the crosslinks. This allows the network to be unlocked or disassembled under controlled conditions. Competitive displacement of weaker biotin analogues by free biotin has previously been demonstrated as a method for reversibly modifying hydrogel networks.

Tuning the properties of the gel

The team can also adjust the physical properties of the hydrogel by controlling the density of its effective crosslinks. This is achieved by mixing active streptavidin nodes with inactive versions in different ratios. Changing this ratio provides a straightforward way to adjust properties such as network connectivity, stiffness and pore size without redesigning the underlying scaffold.

By tuning the internal structure of the gel, the platform could accommodate and immobilise functional proteins with widely different molecular sizes.

Together, these features are intended to distinguish the hydrogel from conventional protein immobilisation systems. Its function, reversibility and physical properties can each be modified independently, creating a reusable platform that can be adapted to different proteins and applications.

Inspired by nature, engineered for synthetic biology

The project was inspired by nature’s ability to construct complex, functional materials through protein self-assembly.

The team aims to repurpose this natural mechanism rather than designing an entirely synthetic material from scratch. The approach reflects the wider aims of synthetic biology by applying engineering principles such as modularity, standardisation and functional reuse to a biological material. Rather than designing a separate material for every application, the team is developing a reusable HET-s scaffold onto which different functional proteins can be immobilised through a plug-and-play system. This separation of the structural and functional components should make the platform easier to adapt, test and optimise. Ultimately, the project demonstrates how naturally occurring biological components can be redesigned into predictable and versatile materials.

From cloning to the Paris Grand Jamboree

Construct design and cloning are now complete, and the team is currently in the expression-testing phase, screening its fibril-forming constructs to find optimal production conditions. The next stages will be fibrillation validation, enzyme attachment via Sortase, and finally assembling and testing the full functionalised gel.

The team will present its work at the 2026 iGEM Grand Jamboree, which runs from 13–16 November at the Paris Convention Centre.

The project brings together students from across 51³Ô¹ÏÍø’s Bioengineering and Life Sciences communities, working across wet lab, dry lab and human practices.

With the project now moving from construct design and cloning into experimental testing, the team’s next challenge is to demonstrate that its unusual biological building block can be turned into a functional, tunable and reusable material.