Ovine pulmonary adenocarcinoma (OPA) is a fatal lung disease of sheep caused by jaagsiekte sheep retrovirus (JSRV). JSRV infects epithelial cells in the lung where it triggers the development of tumours that slowly grow to obstruct the airways leading to difficulty breathing, wasting and eventually death. OPA is an important disease affecting sheep flocks in the UK and many other countries, leading to significant animal suffering and severe economic losses to affected farms. OPA was first described in South Africa almost 200 years ago; however, there are no reliable methods available for diagnosing or treating the disease and there is no vaccine available. The aim of our research is to increase knowledge about the ways JSRV interacts with sheep lung tissue to cause OPA and then to exploit that knowledge to devise new methods for controlling the disease. For example, more detailed understanding of the pathogenesis of OPA will provide information that can be used to develop new diagnostic tests or vaccines to control the spread of the disease in farmed sheep. In a wider context, studies on the mechanisms underlying OPA have the potential to reveal new insights into cellular processes involved in lung physiology, including regulation of respiratory epithelial cell growth and proliferation, lung fluid regulation and respiratory immunology. The information gained may lead to advances in understanding human lung cancer as well as the sheep disease. Our current research on OPA is focussing on two main areas. First, we are studying the molecular pathogenesis of the disease by using RNA-Seq to define the changes in host gene expression in the infected lung that occur during JSRV replication and oncogenesis. Second, we are working directly with affected flocks to devise methods that can be used to identify infected sheep before the clinical signs of disease appear. Currently we are exploring the use of ultrasound scanning of sheep flocks to identify small tumours that are otherwise subclinical.These two projects are interlinked. The work with farmers has involved the creation of a bank of tissues and sera from sheep with OPA that are crucial for our studies on the molecular pathogenesis of the disease. In turn, by increasing our understanding of the host response to JSRV infection and tumour growth, we hope to identify molecules that can serve as diagnostic targets for identifying infected animals and flocks. This combined approach will enable the results of laboratory studies to be applied most effectively to solving this important agricultural problem.