Design, Build and Test of novel bacteria-delivered proteins for cancer therapy

2026-07-22

Conventional cancer therapies have many limitations that could potentially be overcome using engineered tumour targeting bacteria as cancer therapeutics. These bacteria have been shown to selectively grow in tumours where they can produce and deliver therapeutic biomolecules (proteins) extracellularly in the tumour microenvironment. However, the delivery of these biomolecules into the cytoplasm of targeted tumour cells remains a challenge, limiting the clinical translation of these therapies. BacStar aims to address delivery challenges by designing multi-part, multifunctional proteins that transport themselves from the interior of the bacterium into the cytoplasm of cancer cells where they can exert therapeutic action. These proteins will integrate protein motifs for transport (using novel cell penetrating peptides) and anticancer activity, which will be assembled using recently developed computational protein design workflows. A modular design-build-test synthetic biology approach will facilitate measurability and experimental throughput. Novel proteins will be tested in vitro and in vivo with high-throughput methods available at host labs. This interdisciplinary approach is enabled by leveraging cutting-edge expertise and technologies in computational protein design from the Bhardwaj and Baker Lab at the Institute for Protein Design, UW (USA) and in bacterial cancer therapy available at the Tangney Lab, UCC (Ireland). An international intersectoral placement at Prokarium (UK) will support the clinical translation of outputs from this project and build my expertise in translational research, which will inform the commercialisation route of this and future projects. My long-term career aim is to develop bacteria-delivered protein therapeutics. BacStar is a significant career opportunity to transition to independence with the active support of world leaders in their fields and gaining industry R&D experience which is key for the advance of these biotherapeutics.

Ireland

2025-12-15