Dr Emily Swindle

• Mast cells
• Viral induced exacerbations of respiratory diseases
• Asthma
• Infection and allergy
• Microphysiological systems / organ on chip

Dr Swindle’s research focuses on building complex in vitro models of the airways incorporating structural cells and immune cells (including mast cells) to determine their role in viral-induced exacerbations of asthma. She has an interdisciplinary approach to her research with close collaborations with Electronic and Computer Sciences. There are 3 main areas of her research

Interaction of Bronchial Epithelial Cells with innate immune cells: Bronchial epithelial cells form a physical, chemical and immunological barrier of the airways which restricts the free passage of solutes and particles from the external to the internal environment. While epithelial barriers are key to maintaining healthy tissue, in many diseases these barriers become disrupted further compromising the tissue and leading to worsening of disease. Focusing on the epithelial barrier of the lungs, my research is focused on understanding the complex interaction between epithelial cells and other resident structural cells of the airway including fibroblast and resident immune cells including mast cells (MCs) during rhinovirus infection in asthma. These models of the airway use differentiated primary bronchial epithelial cells (BECs) and MCs from cord blood as well as cell lines. This will allow the elucidation of the complex interactions between resident immune cells and structural cells of the airways in the context of asthma exacerbations.

Understanding the role of mast cells in innate immunity: Mast cells are tissue-resident immune cells that are classically associated with the early phase reaction in allergic asthma. However, over the past 30 years there has been a growing realisation that mast cells are key drivers of innate immunity. Lying at the interface between the internal and external environment they sense pathogens and are key to the recruitment of inflammatory cells. While their role in bacterial induced immunity is established their role in viral immunity is not so clear. Current research is focused on elucidating the contribution of mast cells to respiratory virus infection including rhinovirus and the contribution of epithelial-derived cytokines on these responses.

Airway epithelial barrier microphysiological systems (MPS) – MPS are miniaturised models that combine microfluidics, engineering and cell biology to recreate certain aspects of organ physiology in vitro and are a promising alternative to conventional models. In collaboration with Prof Hywel Morgan an “airway barrier on chip” MPS that can monitor epithelial barrier integrity in real-time using electrical impedance spectroscopy (EIS) has been developed [9]. The system uses microfluidics to recapitulate interstitial flow and includes a means for time-dependent sampling of cellular secretions. Monitoring the cells in real time with integrated electrodes provides data on the formation and disruption of the airway epithelial barrier. Lately the system has been developed to include droplet microfluidics for collection of cellular secretions which can provide time-dependent measurements of epithelial responses during differentiation and environmental exposure. New methods for delivery of challenges and compounds in a physiologically relevant manner to the apical surface have been developed using surface acoustic wave technology that generates aerosols. Combining microfluidics and cell biology provides a MPS that more closely recapitulates the physiological environment of the lung for understanding human (patho)physiological mechanisms, providing more predictive pre-clinical models for drug discovery and developing personalised medicine strategies.