Tick saliva protein could one day help treat inflammatory diseases

A team of researchers at the ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) has for the first time synthetically produced anti-inflammatory proteins found in tick saliva, a promising step towards new therapeutic treatments.

Evasins, as the proteins are known, act in human blood to suppress a class of transmitter proteins, which is why when bitten, we often don’t notice a tick has burrowed into our skin. Scientists now want to see how these proteins can be used for treating human diseases, including potential application for lung inflammation in respiratory illness, such as COVID-19.

‘Ticks have a terrible reputation – they are not very nice to look at, need to suck blood to survive and are responsible for transmitting bacteria that cause severe diseases, such as Lyme disease in humans,’ said Professor Richard Payne, an ARC Future Fellow and Deputy Director at CIPPS, who is based at The University of Sydney. ‘But to a medicinal chemist, ticks are amazing creatures.’

Ticks have evolved an impressive arsenal of biologically active salivary proteins they pump into the bite sites on their hosts. Among these are various pain-killing agents and some of the best blood-thinning molecules known.

‘In order to avoid detection, ticks also produce small protein molecules that suppress the inflammatory response. These proteins are called the 'evasins' because they help the tick evade immune detection. This means they can feed for days without the host knowing they are attached,’ Professor Payne says.

In the past, evasins have proven difficult to isolate, so the researchers, led by CIPPS Research Fellow Dr Charlotte Franck, built the proteins from scratch in a feat of synthetic chemistry, something that no one else had ever been able to do. They discovered that sulfate molecules attached to evasins give the proteins a powerful kick.

‘Armed with this knowledge, evasins could potentially be repurposed to suppress chemokine-driven inflammation in human disease,’ Dr Franck says.

‘We are nowtrying to engineer these sulfated evasin molecules to make them more stable in blood. We can then start to explore how effective they could be for a range of inflammatory conditions in the clinic.’

The findings were part of Dr Franck’s doctoral research and was funded by an ARC Discovery Project and NHMRC Project Grant. The CIPPS team will continue to build on this knowledge to try to make the sulfated evasins more effective.

 

	‘Life has had billions of years to exquisitely fine-tune proteins, such as Evasins, for particular tasks. We have an amazing opportunity now to understand how they work and seek innovative ways to apply them to challenges in medicine and other areas to benefit humanity.’ Professor Richard Payne.