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Personal profile

Research interests

Our research focuses on understanding the mechanisms of inflammation and inflammatory disease.

Cell biology of immune cells

My research group is interested in innate immunity including macrophage and microglia inflammatory responses. In particular, we have an interest in molecular signalling pathways, including reactive oxygen species and the role of hypoxic regulation, underlying the activation of the NLRP3 inflammasome and the production of the inflammatory cytokine interleukin 1 (IL-1Beta).

The production of bioactive IL-1Beta is a tightly controlled multi-step process: first IL-1Beta is produced as an inactivate precursor 31 kD pro-IL-1Beta, this is cleaved to produce bioactive 17 kD IL-1Beta and then finally the bioactive IL-1Beta. The processing and cleavage of the IL-1Beta precursor is achieved by caspase-1 activated within a multi-protein complex termed the NLRP3 inflammasome. We have specific interest in the pathways leading to activation of the NLRP3 inflammasome activation in macrophages and microglia.

Sites of inflammation exist under hypoxic conditions where changes in oxygen levels alter the phenotype of cells and the inflammatory response.  The research group is interested in understanding how hypoxia regulates inflammatory responses, in particular inflammasome responses, compared to standard tissue culture conditions.  The Advanced Hypoxic facility was funded by the BBSRC ALERT14 equipment call.

Our research is funded by the EPSRC, BBSRC and the University of Bath.

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Projects 2005 2020

MRC P2D - Industry Challenge Workshop

Mackenzie, A.

1/08/1831/01/19

Project: Research council

MRC P2D - Showcase Event

Mackenzie, A.

31/03/1831/10/18

Project: Research council

Baths
Oxygen
Wales
Electron Spin Resonance Spectroscopy
Brain

The P2X7 Interactome

Mackenzie, A.

17/01/1316/01/16

Project: Research council

Adenosine Triphosphate
Macrophages
Purinergic P2X7 Receptors
Inflammation
Proteins

Research Output 2001 2018

4 Citations

De novo mutations in GRIN1 cause extensive bilateral polymicrogyria

Mackenzie, A., Fry, A., Thomposon, B., Fawcett, K., Zelnik, N., Shemer-Meiri, L., cushion, T., Mugalaasi, H. & Stoodley, N., 22 Jan 2018, In : Brain : A Journal of Neurology.

Research output: Contribution to journalArticle

Open Access
File
Mutation
N-Methyl-D-Aspartate Receptors
Missense Mutation
Exome
Polymicrogyria

Fluorescence based Tool to Detect Endogenous Peroxynitrite in M1-Polarized Murine J774.2 Macrophages

Weber, M., Mackenzie, A. B., Bull, S. D. & James, T. D., 4 Sep 2018, In : Analytical Chemistry. 90, 17, p. 10621–10627 7 p.

Research output: Contribution to journalArticle

Open Access
File
Peroxynitrous Acid
Macrophages
Reactive Oxygen Species
Fluorescence
Oxidative stress
Open Access
File
Inflammasomes
Lipopolysaccharides
Inflammation
Illness Behavior
Depression

Editorial: roles of ion channels in immune cells

Stokes, L., MacKenzie, A. B. & Sluyter, R., 15 Feb 2016, In : Frontiers in Immunology. 7, 48.

Research output: Contribution to journalArticle

Open Access
File

The profile of P2X7 receptor expression and properties in polarized primary mouse microglia cultures

Jackson, M., Wickens, R., Bailey, S. & Mackenzie, A., 2016, In : Journal of Psychopharmacology . 30, Abstract Supplement to volume 8, p. A98

Research output: Contribution to journalMeeting abstract

Purinergic P2X7 Receptors
Microglia
Lipopolysaccharides
Ethidium
Adenosine Triphosphate

Thesis

The Development of Biological Therapeutics

Author: Ali-Hassan, S., 31 Dec 2013

Supervisor: Mackenzie, A. (Supervisor) & Watts, A. (Supervisor)

Student thesis: Doctoral ThesisMPhil

File

The Functional Expression of N-Methyl-D-Aspartate Glutamate-Type Receptors by Megakaryocytes and Platelets

Author: Hobbs, C., 1 May 2010

Supervisor: Mackenzie, A. (Supervisor)

Student thesis: Doctoral ThesisPhD

File

The role of fast ATP-Gated P2X receptors in inflammation

Author: Moore, S., 1 Dec 2008

Supervisor: Mackenzie, A. (Supervisor)

Student thesis: Doctoral ThesisPhD

File

The role of NLRP3 signalling in the pathology of depression

Author: Wickens, R., 1 Mar 2017

Supervisor: Mackenzie, A. (Supervisor) & Bailey, S. (Supervisor)

Student thesis: Doctoral ThesisPhD

The Role of Phosphatidylinositol 3-Kinase in P2X7R Gated Signalling in T Lymphocytes

Author: Foster, J., 31 Jul 2012

Supervisor: Ward, S. (Supervisor) & Mackenzie, A. (Supervisor)

Student thesis: Doctoral ThesisPhD

File