Active Guidance Beads: engineering positional information for human tissue

The problem

Roughly 90% of drugs that look promising in animal models fail in clinical trials. Two upstream causes drive this: animal biology is not human biology, and human cell culture models are often not reproducible or spatially organised.

During development, cells read their position in the body from precise, graded concentrations of signalling molecules called morphogens. In the lab, we can rarely reproduce this. Instead, morphogens are typically added to a dish as a uniform bath, and nobody measures what an individual cell actually experiences. The result is human cell models that are variable and lack the regional identity seen in real tissue.

Our approach

We are developing Active Guidance Beads (AGBs), cell-sized hydrogel beads that release signalling molecules from defined positions to recreate the concentration gradients cells use to determine their identity during development. Rather than bathing cells in a uniform dose, AGBs let us impose a controlled, spatially organised signal, closer to how the body actually does it.

Our research programme is organised around three complementary directions:

• Measure: quantifying, at the level of single molecules, how much signal is released and how it spreads, so we know precisely what cells are experiencing rather than assuming it.
• Control: building beads that respond to cues from the cells themselves, so signal release can be tied to tissue conditions rather than delivered on a fixed schedule.
• Build: using positioned beads to impose multiple signals at once, testing whether this can generate the regional diversity of cell types that uniform culture methods cannot reach.

These three directions are designed to be independent and mutually reinforcing rather than sequential, each with its own value, so the programme does not depend on any single one succeeding.

Why it matters

Our first application area is motor neuron disease (MND/ALS). Standard stem cell differentiation protocols tend to produce one regional subtype of motor neuron, limiting how well lab models capture the diversity of neurons affected in disease. By imposing spatially controlled signals, we aim to generate more regionally diverse and physiologically representative motor neuron populations for disease modelling.

More broadly, we see this as a metrology and engineering problem as much as a biology one: if we can measure and control the signals cells receive with precision, we can build human tissue models that are more reproducible and more informative, for MND and beyond.

Team and collaboration

The project is led by Alex Mason (School of Chemistry and Molecular Bioscience, Molecular Horizons, University of Wollongong), bringing together capabilities in programmable biomaterials, droplet microfluidics and single-molecule measurement. It draws on collaborations across iPSC disease modelling, developmental biology and biophysics, and structural and synthetic biology.

This work is early-stage and non-clinical. It is not yet a therapy or a diagnostic tool.