Jonathan Heddle, PhD is Head of Bionanoscience and Biochemistry Laboratory at the Malopolska Centre of Biotechnology, Jagiellonian University in Kraków, Poland. IIOL talks to Dr. Heddle about his research project creating ultra-stable gold-coordinated protein cages and their possible future applications.

How did your research experience in Poland begin?

Dr. Heddle: While I was working in Japan, I learnt about an opportunity in Kraków, with the potential for good funding and support. These are crucial for research to succeed but not always easy to find. It turns out that there are good opportunities in Poland for scientists with vision.

What is your research?

Dr. Heddle: A large part of our research is in the field of bionanoscience. For us, this means trying to design and build functional biological nanomachines and nanoscale structures that can be programmed to carry out desired functions, particularly related to treatment of disease.

In our case for example, we are trying to develop new DNA origami structures that may even be useful for constructing artificial cells. But our most advanced work right now is a novel protein cage that we made. It is just 22 nanometers in diameter (a nanometer being one billionth of a meter or something like one hundred thousand times smaller than the diameter of a human hair). These cages are extremely stable (they survive boiling temperatures) but easily break down in conditions similar to what is found in our own cells. If the hollow interior is filled with a drug then this has obvious potential for drug delivery to our cells and we are interested in now finding ways to target it to cells affected by age-related diseases.

How advanced is your research?

Dr. Heddle: Our research is a very new area and is a platform from which other things may grow, so that question is difficult to answer. Computer science can be a good analogy: If you asked people two decades ago if advanced computing “intelligence” would be useful in medicine, it may have been difficult to say. Now, we use artificial intelligence to analyze medical data and diagnose patients. That’s a good example of developing something fundamental, a platform: it is the core technology that allows further developments, sometimes years later. Bio-nanoscience is still at this very early stage, we are building its core capabilities.

The structures researchers are able to make now are relatively simple. But using DNA, and a technique called DNA origami, it has already been proven possible to build box-like “nanorobots” that can be programmed to open in response to particular molecular signals (including disease signals). The potential for putting a toxic drug in the box and only releasing it in the vicinity of a diseased cell is obvious.

Ultimately, the most sophisticated machines in nature are proteins (just think of the amazing things enzymes can do) and while it is harder to engineer programmable protein structures, we are getting there, with protein cages being a promising field at the moment. These are artificial protein “balls” with hollow interiors. The hope is that we may be able to engineer such cages so that they carry drugs into cells and then only release the drugs when certain conditions are met. In other words the ultimate, targeted drug delivery system. There are many age-related diseases where this could be useful. The most obvious would be in numerous cancers where drugs, if not exquisitely targeted, end up killing healthy cells, often with severe side effects.