Building bioengineered tools for better brain health
Epilepsy is a serious chronic brain disease characterised by recurrent seizures. It is one of the most common serious neurological conditions, affecting about 60 million people globally. “There remain urgent and unmet needs for the treatment of such neurological diseases,” explains PRIME(opens in new window) project coordinator Deirdre Kilbane from the Walton Institute(opens in new window) at South East Technological University(opens in new window) (SETU) in Ireland.
Autonomous implantable living cell systems
The PRIME project sought to address this challenge through a pioneering novel technique. Bringing together seven expert international partners in multidisciplinary fields including synthetic biology, computer science, communication engineering and nanomedicine, the project set out to develop an autonomous implantable living cell system, capable of actuating epileptic seizure suppression. The idea is that these cells, implanted into the brain, can predict epileptic seizures and release therapeutic molecules in real time. A key focus of the project involved modelling and simulating the molecular communication pathways relevant to the onset of epileptic seizure. This was led by the Walton Institute at SETU. Aarhus University focused on the regulation of gene expression and the onset of epileptic seizure, while the Royal College of Surgeons in Ireland looked into the molecular design, implementation and functional validation of engineered neural cells. At the University of Ferrara, scientists investigated engineering mammalian cells with molecular computing functions. Project partners Tampere University provided expertise in microfabrication, membrane technology and encapsulation of the biocomputing cells. Meanwhile, project partner omiics used their expertise in low-input RNA sequencing and bioinformatics analysis, while EPOS-IASIS provided insights into nanomanufacturing, nanomaterials, nanomedicine and genetic technologies.
Artificial intelligence to optimise response and performance
Through this cross-disciplinary collaboration, significant progress has been achieved. Key developments include molecular communication simulation, cell engineering and implantable device design. A prototype design tool for engineering cells uses artificial intelligence (AI) and integrates molecular communication simulations that utilise biophysical and statistical mechanics modelling. “Large experimental datasets provided at each stage of development enabled us to use AI to accurately predict and optimise response and performance,” notes Kilbane. Partners successfully engineered mammalian ARPE-19 cells with molecular computing functions capable of detecting seizure-related signals (tsRNAs) and triggering the release of a therapeutic molecule (GDNF). The project’s work has resulted in a dozen publications, most recently a paper(opens in new window) outlining some of the work carried out in developing molecular communication propagation models and implantable biosensing devices.
Diagnosing and monitoring neurological diseases
PRIME consortium partners continue to gather results and conduct analysis. Next steps include in vivo testing to ensure that the team is in a position to fulfil its key objectives. “This has been an innovative project with close collaboration between the partners,” says Kilbane. “We look forward to continuing our ongoing work over the final months of PRIME ahead.” Overall, the project represents a significant milestone in improving the lives of those living with epilepsy and other chronic neurological diseases. Indeed, the concept of implanting programmable synthetic cells that mimic electronic computing circuits could be extended to treat other neurological conditions. “The innovations pioneered by PRIME have the potential to revolutionise how we diagnose and monitor neurological diseases by detecting biomarkers efficiently,” adds Kilbane. “We have taken a huge leap towards building bioengineered tools for better brain health.”
