Lakshmi Narasimha Murty Suri
Srinivasa Reddy Kunchala
Erin McGillick (co-supervised with Dr Janna Morrison)
The laboratory’s key aim is to understand the evolution, molecular function and regulation of the pulmonary surfactant system in a range of animal and disease models. Surfactant is a lipoprotein mixture at the air-liquid interface of the lung that is critical for lung function and to protect the lung from foreign organisms and particles.
Lysosomal storage diseases (LSD) are a group of more than 70 devastating genetic diseases. They occur because of a defective enzyme that leads to accumulation of waste products within lysosomes which are responsible for cellular waste disposal. This accumulated waste disrupts the function of cells leading to a wide variety of symptoms across different diseases and different individuals, including significant respiratory pathology. How exactly the increased storage leads to different disease manifestations is currently not understood. Specifically we aim to identify the causes and mechanisms of respiratory dysfunction and the role of the pulmonary surfactant system in LSD. We hypothesise that the accumulation of storage material in endosome-lysosome organelles disrupts the intracellular architecture and function of alveolar epithelial cells. This impacts the formation of lamellar bodies responsible for producing pulmonary surfactant which is critical for breathing and fighting respiratory infections. For more information, contact Dr Emma Parkinson-Lawrence.
Babies born preterm or born small for their gestational age are at an increased risk of developing respiratory distress because their pulmonary surfactant system is not fully developed. Using a range of animal models, we wish to establish the mechanisms and timing of surfactant maturation during early and late gestation in relation to environmental factors that lead to intrauterine growth restriction (IUGR). Control and growth-restricted lung tissue at various developmental stages will be analysed for alterations in surfactant protein and gene expression as well as alterations in gene expression of transcription and growth factors involved in the regulation of surfactant protein expression. An increased understanding of the factors that regulate surfactant maturation in this complex condition will lead to improved treatment of mothers at risk of delivering a preterm infant. For more information, contact Professor Sandra Orgeig or Professor Janna Morrison.
The surfactant system contains specific surfactant proteins (SP) – SP-A & -D which belong to the family of collectin proteins that are involved in the innate host defence system. Birds harbour many respiratory pathogens to which they are immune, yet we understand little about their pulmonary innate immune proteins. Chickens appear to lack the SP-D gene, but instead they have an additional SP-A-like gene, named SP-A2. We are currently investigating the evolution of the pulmonary collectin proteins among the birds and more broadly among the vertebrates to establish whether these are avian-specific genetic events that may be related to the unique evolutionary trajectory of the unidirectional tubular respiratory system of birds. Correlating molecular evolutionary changes of proteins with the physiological evolution of the lungs will provide insights into crucial functional protein motifs. For more information, contact Professor Sandra Orgeig .