Granulocytes constitute a class of white blood cells that are responsible for the continuous surveillance of and defence against microbial infections; these cells do not rely on an immune memory (i.e. past infections). Granulocytes not only immobilise and degrade pathogens as a first line of defence, but they also play a central role in immune regulation to coordinate adaptive immune responses. Owing to the short lifespan of these cells, a constant stream of granulocytes have to be regularly generated from blood stem cells (i.e. granulopoiesis) to guarantee a steady-state of immune surveillance and protection. The body's demand for granulocytes is further heightened during microbial challenge, requiring higher levels of "stress-granulopoiesis". This process of blood stem cell expansion and specialisation into mature granulocytes (granulopoiesis) can be specifically induced by signalling proteins called cytokines. Recombinant (exogenously produced) cytokines have thus enabled the treatment of inherited or induced immunodeficiencies. Recombinant cytokines however suffer huge pharmaceutical drawbacks: they have to be stored in refrigerators and are easily degraded. In this design project, we aim to create potent granulopoietic proteins with novel sequences and structures that renders them: ultra-thermostable, degradation stable, cheaper to produce and purify, have longer shelf-life, have longer in vivo half-life, more soluble, and orally bioavailable. Our computationally-designed protein molecules have shown high specific activity in inducing granulopoiesis in human stem cells and in different animal models.
We are currently developing protein-based anti-bacterials and antifungals that possess that face minimal resistance and are biodegradable agents. These proteins can be used as human and veterinary therapeutics, anti-infective agents, food preservatives, and plant-production agents.