The primary focus of my research is the analysis of complex mechanisms of action of the innate immune system. In particular, we aim to understand how we recognise the earliest stages of an infection or tissue injury through the signalling pathways that are initiated by the invading pathogen or irritant. My research is mainly focused on elucidating the signalling events that occur downstream of Pattern Recognition Receptors (PRRs), these receptors are the primary surveillance system for the detection of pathogens and are crucial to the activation of host defence. The purpose, is that by providing a greater understanding of the basic signalling processes of the human innate immune response, we can apply that knowledge to various diseases which would ultimately lead to more profound treatment options for patients.
We are currently working on two programmes of research. Ongoing collaborations internationally and with the Dept. of Genetics and the School of Biochemistry and Immunology, have led to a significant advance in the understanding of the role of the immune system in Age Related Macular Degeneration (AMD). Our research has identified IL-18, a cytokine induced by the PRR, NLRP3, as an anti-angiogenic factor which can downregulate vascular endothelial growth factor. Augmentation of IL-18 may therefore prove useful as a therapy to prevent progression of abnormal vessel growth into the back of the eye, which causes immediate central blindness.
This work on AMD led to a growing interest in the workings of the immune system in relation to age. Human neonates are highly susceptible to infections by bacteria, fungi and viruses and as a result infection remains the single most common killer in early life. Based in the National Children’s Research Centre (NCRC), we are investigating the PRR signalling pathways in newborns, infants and children. These pathways are altered compared to the adult immune response. Our aim is to analyse the pathways that may contribute to their increased susceptibility to infectious agents and provide a greater understanding of the young human innate immune response.
For further information about Dr Sarah Doyle please view her CV Profile
Confocal image of immune protein interactions within a cell following a response to bacterial cell wall component LPS