Dr Tara Sutherland

Biography

I graduated with a BSc with Honours degree from the University of Melbourne in Australia before embarking on PhD in Pharmacology studying oestrogen metabolites in cancer using breast tumour models. After a stint studying ligand-receptor modelling at Monash University, I moved to Edinburgh to begin learning all about immunology and how the lung responds to infections, allergens and injury.

I obtained an Asthma UK and Medical Research Fellowship and moved to the University of Manchester to develop and utilise models of allergic airway pathology to study immune responses and extracellular matrix remodelling in the lung. Now in 2022, I am excited to have joined the University of Aberdeen as a Lecturer and will continue to build my research group with the aims of uncovering key immuno-matrix networks that drive lung disease.

Research Overview

Communication between the extracellular matrix and immune cells
controls the tipping point between lung health and disease

The extracellular matrix (ECM) is the non-cellular part in all tissues and organs and is made up of molecules like glycosaminoglycans & proteoglycans (e.g. hyaluronan, chondroitin sulfate, heparin sulfate), fibrous proteins (e.g. collagen, elastin) and mucins. More than just physical architectural scaffold within our tissues, the matrix is biologically active with many functions including the ability to direct cell migration and influence cell function. In turn, tissues and immune cells provide critical cues that work together to maintain a healthy tissue matrix. However, if communication and interactions between the matrix and cells is compromised in light of infections, injury, inflammation or insults tissue pathology ensues.

Immuno-matrix in lung health and disease

My lab is focussed on understanding the cross-regulatory pathways between immune cells, stromal cells (e.g fibroblasts) and the matrix that determines the balance between health and disease in the lungs. In order to study these aspects of our research we need to be able to observe what is going on in the tissue microenvironment and therefore our research heavily features high dimensional imaging and analysis (below), and spatial technologies.

Hyperion imaging mass cytometry – mouse lung stained with a panel of matrix, immune and stromal cell markers. Single cell clustering allows for analysis of cell-cell and cell-matrix interactions spatially in the lung

Current Research

Having recently moved my lab to Aberdeen from the University of Manchester, I continue to work with my PhD students and PDRA on collaborative projects primarily based in Manchester, as well as setting up exciting new research here in Aberdeen.

Role of chitinases during fungal host-defence in the lung
One family of molecules that appear crucial in maintaining tissue health through balancing immune responses and remodelling of the extracellular matrix are the chitinases and chitinase-like proteins (CLPs). Chitinases act as host-defence enzymes through their ability to degrade chitin and chitin-containing pathogens (e.g. fungi, parasites, allergens). In collaboration with Prof Munro’s lab in Aberdeen we are looking at how chitinases influence host defence against fungal pathogens in 3D lung cultures – PhD Opportunity.

Pathological matrix remodelling in asthma: role for chitinase-like proteins, innate immune cells and fibroblasts
CLPs are derived from chitinase gene duplication but have lost enzymatic activity throughout the evolutionary process. Research is still trying to piece together the functions of CLPs but we know they are highly secreted in inflammation, tissue injury and repair, infections and fibrosis. We revealed the ability of CLPs to regulate immune responses and the ECM in the lung during parasite infections^1,2. Now we are investigating how CLPs influence the matrix and immune cell cross-talk in asthma using in vivo mouse models, human lung tissue resections and in vitro assays³

Increased expression of murine CLPs Ym1 and Ym2 following chronic administration of a cocktail of allergens (DRA). Parkinson et al (2021) Immune Cell Biol

IL-13-hylauronan axis during viral infections in the lung
The type 2 arm of the immune response is associated with both helminth infections and allergic inflammation but also critical in orchestrating tissue repair and fibrosis. However, in collaboration with the University of Virginia and University of Manchester, we recently found that type 2 cytokine IL-13 as a driver of severe COVID-19 pathology through regulation of ECM component hyaluronan⁴. Currently, we are trying to mechanistically understand the IL-13-hyaluronan axis in the lungs, and why this pathway is important in pulmonary diseases.

Immunostaining for hyaluronan (green) in the lungs from patients with or without COVID-19. Donlan et al (2021) JCI Insights.

Relevant References
1. Sutherland et al, Chitinase-like proteins promote IL-17-mediated neutrophilia in a trade-off between nematode killing and host damage. Nat Immunol; 15(12), 1116-25 (2014)

2. Sutherland et al, Ym1 induces RELMα and rescues IL-4Rα deficiency in lung repair during nematode infection (2018) PLoS Path;14(11)e1007423.

3. Parkinson et al The magnitude of airway remodelling is not altered by distinct allergic inflammatory responses in BALB/c vs C57BL/6 mice, but matrix composition differs. (2021) Immunol Cell Biol 99(6):640-655

4. Donlan et al. IL-13 is a driver of COVID-19 severity. JCI Insight; 6(15):150107 (2021)