THE INFLAMMATORY SIGNALLING GROUP

Research Overview

We are interested in understanding the biology of aging, the pathways responsible for immune-mediated inflammatory conditions and the mechanisms of cell death.  The Inflammatory Signalling Research Group has expertise in innate immune cells, in particular macrophages, and more recently retinal pigment epithelial cells.

The group employs a range of techniques including in vitro cell culture, protein biochemistry (quantitative fluorescent western blot, immunocytochemistry, ELISA), patch clamp electrophysiology and fluorescent microscopy. We led a BBSRC application to fund an advanced hypoxic facility hosted by the University Material and Chemical Characterization Facility.

Enquiries are welcome from self-funded PhD students and postdoctoral researchers interested in fellowship applications.

Current Projects.

Reactive Oxygen Species. Recently, we have worked with Prof. Tony James to develop the application of new fluorescent peroxynitrite probes in innate immune cells and evaluated responses under inflammatory conditions.  This work has led to an interest in the use of these diagnostic tools to detect the biomarkers of healthy aging as well as immune disease.

1. Weber M, Han H-H, Li B-H, Odyniec ML, Jarman CEF, Zang Y, Bull SD, MacKenzie AB, Sedgwick AC, Li J, He X-P, James TD. Pinkment: a synthetic platform for the development of fluorescent probes for diagnostic and theranostic applications Chem Sci., 2020,11, 8567-8571 https://doi.org/10.1039/D0SC02438D From the themed collection: Most popular 2019-2020 analytical chemistry articles
2. Weber M, Yamada N, Tian X, Bull SD, Minoshima M, Kikuchi K, Mackenzie AB, James TD. Sensing Peroxynitrite in Different Organelles of Murine RAW264.7 Macrophages With Coumarin-Based Fluorescent Probes. Front Chem. 2020 8:39. doi: 10.3389/fchem.2020.00039.
3. Weber M, Mackenzie AB, Bull SD, James TD. Fluorescence-Based Tool To Detect Endogenous Peroxynitrite in M1-Polarized Murine J774.2 Macrophages. Anal Chem. 2018 90(17):10621-10627. doi: 10.1021/acs.analchem.8b03035.

Tissue Engineering. We are developing a new retina-on-a-chip technology in collaboration with Dr Paul De Bank to address key challenges in studying retinal function in vitro.  We have a particular interest in the relationship between differentiated retinal pigment epithelia (RPE) and the micro-environment including interaction with the extracellular matrix within the Bruch’s membrane, conditions associated with inflammatory disease and local oxygen transport. 

Age-related macular degeneration (AMD) impacts 600,000 people in the UK alone (https://tinyurl.com/5btjpxmz, accessed 2021). There are two forms of AMD; Dry AMD resulting from the progressive death of retinal cells in the macula of the eye and wet AMD due to overgrowth of blood vessels into the macula. We are studying pathways that lead to cell death and inflammatory responses in human RPE found in the macula.  A recent Dunhill Medical Trust funded project aims to understand the functional role of the gasdermin family of proteins in RPE as a potential new drug target to treat retinal disease.

Scleroderma is an auto-immune disease predicted to impact on 2.5 million people worldwide (https://www.sruk.co.uk/scleroderma/, accessed 2021).  We are currently working with Dr Sergey Smirnov (Pharmacy & Pharmacology, Bath), Dr Jay Suntharalingam and Dr John Pauling (Royal United Hospital, Bath) to understand the link between scleroderma and the development of pulmonary arterial hypertension. 

Flower VA, Barratt SL, Hart DJ, Mackenzie AB, Shipley JA, Ward SG, Pauling JD. High-frequency Ultrasound Assessment of Systemic Sclerosis Skin Involvement: Intraobserver Repeatability and Relationship with Clinician Assessment and Dermal Collagen Content.  J. Rheumatol. 2021 48(6):867-876.

Teaching Overview

I contribute to teaching undergraduate and master level degrees  with a mixture of traditional teaching approaches (e.g. Lectures, Workshops) combined with digital technologies such as Peerwise to develop knowledge and skills. I am interested in the benefits of peer-to-peer learning and flipped teaching approaches to support student learning in the areas of human physiology, cell biology and inflammation.  

Convenor of the Receptors to Genes (Year 2), Pharmacology Placement Landmark Dissertations (Year 3), and Pharmacology Communication Skills in Pharmacology (Year 3/4).  Previously, Bath lead of the GW4 BioMed MRC doctoral training programme and the Bath Pharmacology Industrial Placement Tutor.

Proceedings of the British Pharmacological Society

Evaluation of the transformative impact of Peerwise as a learning tool. Edmead, A. Mackenzie. 2017.

Going for gold: using Peerwise for deeper learning and formative feedback. Edmead, A. MacKenzie. 2016.