Second stop - the United Kingdom

In England I was going to visit people relating to two different areas; silk proteins and protein electrochemists.

Prof Fritz Volrath and Dr Chris Hollande study how insects process silk proteins to make different materials. From their insights into how spiders spin their silk they have established a company Oxford Biomaterials which uses silkworm cocoons. The firstly reconstitute the silk and then use the protein to produce new materials for regenerative medicine. Their fine control over the mechanical properties of the silk protein allows them to produce unique materials, some of which are currently under clinical trials. 

The second skill set that I was seeking to learn more about is protein electrochemistry. England in particular Oxford University has a very rich tradition in this area. It was in the Inorganic Chemistry Laboratories at Oxford that the breakthrough was made by Allen Hill and co-workers which enabled the development of blood glucose meters as we know them today. These sensors are what is known at mediated sensors (or second-generation biosensors). 

A bioinspired nitric oxide sensor for asthmatics

To understand how I have used my Churchill Fellowship, it will be helpful to understand some of the more technical aspects about the nitric oxide sensor that I have developed. Firstly, the sensor is “bio-inspired” this mean we draw on the knowledge of naturally occurring systems and seek to incorporate those lessons into our sensors. The sensor I have developed is inspired by a haem protein which senses nitric oxide and leads to blood vessel dilation in our bodies.  The best known haem protein is haemoglobin which is found in our blood and transports oxygen to our tissues. Intriguingly, there are many other haem proteins found in nature, some of which do not bind oxygen (O₂) at all but are able to detect and respond to nitric oxide (NO) a very similar diatomic gas.

The unique thing about our sensor is that it uses a silk protein from honeybees. Honeybee silk is very different from the better known silks such as spider silk and silk worm silk. Dr Tara Sutherland at CSIRO has been exploring these silks for biomedical applications. Our approach is to the silk as the protein scaffold, thereby wraping the haem group within as silken coat. The silk both stabilises the haem centre but also can crucially control it’s reactivity as well. You normally think of silk as fibres, however we can make our silk proteins into a range of other material formats such as films and sponges. It is the transparent, malleable films which have proved to be the best suited for biosensors.

The final point about the sensor is that it is an electrochemical sensor in which nitric oxide binding to the protein is measured electrochemically. This is a similar concept to that used in the best known biosensor – the glucose monitor which has revolutionised the lives of diabetics.

In my fellowship I have been afforded the opportunity to deepen my knowledge of bioinorganic chemistry (the study of metals in proteins), I have been able to connect with some of the leading silk groups in the world to share our ideas with them and to work with a leading synthetic chemist to develop new metal centres to incorporate into my nitric oxide sensors.