Led by Professors Shoumo Bhattacharya and David Hodson at the University of Oxford, this project will take inspiration from tick saliva to develop a defence mechanism for beta cells transplanted into people with type 1 diabetes. This research could reduce the need for immunosuppressing drugs, leading to longer-lasting and more successful beta cell transplants.  

Background to the research project – taking evasin action

Some people with type 1 diabetes can have insulin-producing beta cells (taken from donors or grown from stem cells) transplanted into them, which replace their own cells that have been destroyed by their immune system. But the immune system often tries to destroy these as well. This means that transplant recipients need to take strong drugs that dial down their immune system, called immunosuppressants.  

And even with immunosuppressants, the immune system still eventually kills off the transplanted cells and most people end up needing insulin again after a few years. 

Transplanted beta cells release chemical signals called chemokines, which act like beacons that lead the immune system to attack them in type 1 diabetes. Researchers have struggled to find ways to block these signals, because there are so many different types of chemokines. 

Parasitic ticks have evolved proteins called evasins which can block a wide range of chemokines, allowing them to bite through skin and feed on blood without being detected by the immune system. Professors Shoumo Bhattacharya and David Hodson think evasins could unlock new ways to block chemokines released by transplanted beta cells, helping them to evade the type 1 immune attack and survive and thrive for longer after transplantation, without immunosuppressants. 

What will the team do in this project?

Professors Shoumo Bhattacharya and David Hodson have already identified the part of the tick evasin that’s responsible for blocking chemokines, called a peptide. In this project, they plan to make its blocking power stronger by adding chemicals to it in the lab. 

Next, to make the peptide last longer in the body, they’ll attach it to parts of antibodies (proteins that protect the body from harm), creating what they’re calling a ‘nanobody’. They’ll also experiment with adding the peptide to other substances to improve its stability and effectiveness. 

After this, they’ll engineer beta cells to produce chemokine-blocking peptides of their own, and test if they’re working by exposing them to chemokines in the lab, and checking whether immune cells spot and attack them. Lastly, they’ll verify all their lab-based findings in mice with type 1 diabetes. 

How will this research help people with type 1 diabetes?

The peptides developed from tick evasin in this project could improve the success of beta cell transplants for people with type 1 diabetes, by giving them a built-in defence mechanism against the immune system. 

They could reduce the need for immunosuppressing drugs, which can make it harder for people to fight off infections, and can even increase the risk of developing cancer. Lowering the risk of side effects from immunosuppressants could ultimately lead to better outcomes for people with type 1 diabetes. 

Professor Shoumo Bhattacharya said:

“Our lab is looking to nature for new ways to treat inflammatory diseases. Ticks have evolved over millions of years to block inflammatory signals called chemokines. Chemokines cause beta cell inflammation which is important in the development of type 1 diabetes and can cause transplanted beta cells to fail.

“We are very excited to receive funding from the Grand Challenge, with which we aim to develop tick-inspired treatments to help people with type 1 diabetes. These treatments could improve the success of beta cell transplants, and prevent type 1 diabetes from developing.”