Principal Supervisor: Prof Corinne M. SpickettLink opens in a new window

Co-supervisor: Dr Alex Cheong (Pharmacy) or Dr Alfred Fernandez-Castane (Engineering)

PhD project title: Rusty cells: redox regulation of cell signalling and responses to stress

University of Registration: University of Aston

Project outline:

Redox balance is a central aspect of cellular function that regulates cell behaviour across many organisms from microbes to mammals. Cells maintain a balance between oxidizing species (such as hydrogen peroxide or superoxide) and antioxidants; changing the balance in either direction affects macromolecular interactions, gene expression, cell differentiation, proliferation or death. These responses are important in a wide variety of fields including antimicrobial resistance, responses to environmental toxins, cell manufacturing (BRIC) and effects of ageing, diet and health. While the general principles are well understood, many questions remain about the precise interactions that control specific processes. My group works on understanding the sensing and effects of redox imbalance at a molecular level in a variety of systems and applications.

The role of redox balance in magnetotactic bacteria (Co-supervisor Dr Alfred Fernandez-Castane). Magnetotactic bacteria produce magnetosomes, structures that contain magnetite (Fe₃O₄) and allow the microbe to align in magnetic fields. Magnetosomes are of great interest as sources of magnetic nanoparticles for biotechnology applications, but knowledge of their synthesis, regulation and biochemical effects is still limited. Evidence is emerging that their production is redox-dependent, they may be redox-active in vivo and have protective effects against environmental stress. Building on expertise in growth of magnetotactic bacteria at Aston, this project will investigate the properties of the magnetosome membrane under different growth and redox conditions to determine how the bacteria avoid lethal oxidative damage from iron-dependent reactions and what antioxidant activities are present. Lipidomic and proteomic studies under different conditions will provide new understanding of magnetosome properties and enable improved magnetosome production.

References:

Development of a simple intensified fermentation strategy for growth of Magnetospirillum gryphiswaldense MSR-1: physiological responses to changing environmental conditions. Alfred Fernández-Castané, Hong Li, Owen RT Thomas, Tim W Overton. New Biotechnol 2018; 46: 22-30

Analysis of SMALP co-extracted phospholipids shows distinct membrane environments for three classes of bacterial membrane protein. Teo ACK, Lee SC, Pollock NL, Stroud Z, Hall S, Thakker A, Pitt AR, Dafforn TR, Spickett CM, Roper DI.

Sci Rep. 2019; 9(1):1813.

Lipid Composition Analysis Reveals Mechanisms of Ethanol Tolerance in the Model Yeast Saccharomyces cerevisiae. M Lairón-Peris, S J Routledge, J A Linney, J Alonso-Del-Real, C M Spickett, A R Pitt, J M Guillamón, E Barrio, A D Goddard, A Querol. Appl Environ Microbiol. 2021; 87(12):e0044021.

BBSRC Strategic Research Priority: Renewable Resources and Clean Growth - Industrial Biotechnology, Understanding Rules of Life - Microbiology, Structural Biology, and Systems Biology, and Integrated Understanding of Health - Ageing, and Diet and Health.

Techniques that will be undertaken during the project:

This project will use a combination of the biochemical, analytical and computational techniques below.

Biochemical techniques: cell culture, enzymatic assays, protein modification, enrichment and characterization, and molecular biology (mutagenesis and generation of fusion proteins).

Analytical techniques: liquid chromatography and mass spectrometry (LC-MSMS), PAGE and western blotting.

Computational techniques: quantitative data analysis, protein identification (proteomics), lipid and oxidized lipid identification (Progenesis and other software), pathway mapping.

Contact: Prof Corinne M. SpickettLink opens in a new window