Researchers at Integrated Biosciences have developed a novel platform that enables millisecond- and micron-level control over previously intractable biological systems, unlocking new therapeutic opportunities in age-related diseases.
The platform combines optogenetics, chemistry, and AI to discover small-molecule therapeutics for age-related diseases.
A new peer-reviewed publication demonstrates the platform’s capabilities by applying it to the integrated stress response (ISR), a key aging and disease-associated signalling pathway implicated in neurodegeneration, cancer, and viral infections.
Benefits of ISR for reducing pathology of age-related diseases
The scientists used optogenetic control to selectively activate the ISR, leading to the discovery of several ISR-potentiating compounds that sensitise stressed cells to apoptosis without inducing cytotoxicity across diverse cell types and stressors — an elusive therapeutic profile not achievable with traditional ISR drugs in development.
The lead compounds identified in the study showed broad-spectrum antiviral activity in vitro, and one compound significantly reduced disease pathology and viral titres in a mouse model of ocular herpesvirus age-related infection.
A powerful new approach to drug discovery
The new platform allows for precise and dynamic control of biological targets and processes, unlocking a powerful new approach to drug discovery.
By integrating programmable, light-responsive domains with automated high-throughput screens, the platform interrogates biological systems with millisecond temporal precision and micron-scale spatial resolution.
This uniquely modular system allows researchers to resolve compound effects in real time, across diverse targets, cell types, and age-related diseases, providing a level of precision and control not achievable with conventional screening technologies.
“Synthetic biology tools like optogenetics allow us to precisely tune complex cellular processes, something traditional drug screening can’t do,” said Maxwell Wilson, PhD, Co-Founder and Chief Scientific Officer of Integrated Biosciences.
“Our platform lets us activate specific targets and pathways with light, generating clean, interpretable readouts and the discovery of high-precision compounds, often with unprecedented mechanisms of action, that were previously inaccessible.”
A major advantage over traditional screening tools
Unlike traditional perturbation agents and pharmacological tools, the platform enables selective, pathway-specific activation without the off-target or systemic confounding effects, generating clean, high-fidelity, on-pathway datasets.
This is especially critical in phenotypic screening and AI-driven discovery, where data quality remains a major bottleneck to extracting meaningful insights.
It also offers a generalisable strategy for discovering small molecules that modulate complex, traditionally hard-to-drug targets and pathways, including age-related diseases.
As the system is modular and tuneable, it can be rapidly adapted to explore a wide range of biological processes with on-pathway, on-phenotype precision – a major advantage over traditional screening tools.
Wilson concluded: “This is only the first demonstration of what our optogenetic platform can do.
“Synthetic biology gives us the control we need to build more accurate, disease-relevant discovery systems. Our goal is to bring this level of precision to other pathways where conventional tools have failed.”