Teaching nature new tricks to fight disease

21 Feb 2020:

For Dr Andrew Care, tiny structures inside living bacteria may hold the key to tackling many diseases. Shaped like miniature soccer balls, these protein nanocages can be modified to accomplish a wide range of tasks, from helping microbes cope with environmental stress to delivering drug payloads inside cancer cells.

‘They’re found in nature and are encoded by genes,’ said Dr Care. ‘This means we can use genetic engineering methods to rewrite this code and give these protein nanocages new and very different functions.’

Dr Care, who is based at the Macquarie University node of the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), applies his background in synthetic biology and nanomedicine to reprogram protein nanocages into tiny tools for the targeted treatment of various cancers and neurodegenerative diseases.

‘I like to take proteins away from their natural “day jobs”, reprogramming them for non-natural applications, like drug delivery’ he said.

Dr Care has been with the CNBP since its beginnings, starting out as a PhD student. In 2018, he was awarded an Early Career Fellowship from the Cancer Institute of New South Wales to develop protein nanocages technologies that can be used to treat cancer.

Dr Andrew Care in the lab (Credit Dominik Kopp Photography)

In one study, Dr Care and his team engineered protein nanocages to self-assemble with a built-in package of photosensitising proteins. When light hits the cages, the protein package converts normal oxygen into a toxic form that kills cancer cells.

Building on the natural functions of protein nanocages, Dr Care is also exploring ways to finely tune these structures. Inside some bacteria, nanocages capture iron, which is toxic to living organisms at high levels, enabling their bacterial hosts to deal with iron-related stress.

‘We’ve reprogrammed protein cages to sequester copper instead of iron, which hasn’t been investigated before,’ said Dr Care.

As copper can help drive the progression and spread of many different types of cancer, capturing and removing it from cancerous cells can potentially slow the growth of tumours. His team are now investigating the anticancer effects of their copper-capturing nanocages through a research project funded by Cancer Australia, the Kids’ Cancer Project and the Australian Lions Childhood Cancer Research Foundation

Dr Andrew Care and colleague Dennis Diaz (credit: Dominik Kopp Photography)

Dr Care is also getting down to the fundamentals of how these structures work, particularly their unique ability to spontaneously self-assemble, which has already led to some big discoveries.

‘We discovered our own nanocage recently, which is exciting,’ he said. ‘We’ve now defined its structure and natural function.’

In 2019, Dr Care and neuroscientist Dr Lyndsey Collins-Praino from CNBP’s University of Adelaide node began to apply protein nanocage technologies to target and treat neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The research project was recently awarded project funds from Brain Foundation Australia and the Dementia Australia Research Foundation.

Dr Care said that working with a wide range of researchers with different skill sets at the CNBP has shaped the way he approaches his research.

‘It’s definitely driven me towards multidisciplinary science,’ he said. ‘I feel that I have gained a broader understanding of different research fields over the years because the CNBP allows me to interact with everyone, from physicists and chemists to biologists and clinicians.’