Before we had settled on a final workflow, our starting point was a simple problem: many useful proteins are hard to work with because they misfold, aggregate, or lose activity.
This matters because proteins are central to biotechnology. They can act as enzymes, reagents, diagnostics, therapeutics, and research tools, but only if they can be expressed, handled, and stored in a functional form. If a protein aggregates easily, even a promising biological idea can become difficult to turn into a useful system.
We became interested in intrinsically disordered proteins, or IDPs, because they offer a different way of thinking about this problem. Unlike structured proteins, IDPs remain flexible and dynamic. Their sequences are often rich in charged and polar residues, which may help them interact with water, reduce aggregation, or keep neighbouring proteins apart.
This led us to the idea of using IDP-inspired sequences as solubility tags. Instead of redesigning every difficult target protein directly, we asked whether a transferable tag could improve the behaviour of a target protein.
Several ideas shaped our early thinking:
- known solubility tags, such as SSB and NEXT/N11;
- de novo IDP-like sequences designed around charge balance and hydrophilic character;
- tardigrade-inspired proteins, which may help protect biological material during stress such as drying;
- possible mechanisms such as entropic bristle effects, protective matrices, or cage-like behaviour around a target protein.
At this stage, the project was still broad. We were not yet sure which target protein, selection method, or validation assay would work best. But the core direction was already clear: generate candidate IDP tags, test whether they improve protein performance, and use the results to guide the next design cycle.
Our early goal was not just to find one working sequence. We wanted to build a workflow that could connect sequence design, experimental selection, and biological interpretation. That remains the central idea behind the project.