Professor Corinne Spickett

Supervisor Details

Contact Details

c.m.spickett@aston.ac.uk

Scientific Background

Research Interests

My research is centred in the field of Redox Biology and Oxidative Stress, and I am an internationally recognized researcher in this field. Redox balance controls many cell signaling pathways leading to cell proliferation, differentiation and toxicity. I am particularly well-known for research on analysis of oxidized phospholipids using mass spectrometry, and recently this has expanded into lipidomics and ox-lipidomics. My group also works on analysis and biological effects of protein oxidation both in vitro and in vivo. A strong current focus is on the structure-function relationship of protein lipoxidation, which involves the formation of adducts of oxidative lipids with proteins, which is important in many inflammatory diseases and cancer.

I led the Horizon 2020 Innovative training network MASSTRPLAN (Mass Spectrometry Training network in Protein Lipid Adduct Analysis) from 2015 to 2019. More information is available on our webpage https://www.masstrplan.org/. I am also a member of AMPL (Aston Membrane Proteins and Lipids group) and a Co-investigator on the international collaborative projects MemBrane and MemTrain, where my role involves support for lipidomic and ox-lipidomic analysis.

Scientific Inspiration

Professor Mike Murphy, MRC Mitochondrial Biology Unit – he does fantastic fundamental science on redox stress in mitochondria that has broad biomedical implications while being amazingly unassuming (as well as funny).

Research Groups

Biosciences Research Group (BRG)

Supervision Style

In three words or phrases: Flexible, supportive but output-orientated.

Provision of Training

I expect to be involved early on and give some hands-on training myself, but want you to develop your own skills progressively and take responsibility for your learning. I will give personal training in LC-MSMS.

Progression Monitoring and Management

I like to be kept up to date regularly with progress (science is exciting) and want you to come to me with good news as well as bad news. I operate an open-door policy and frequently have impromptu chats for problem solving and updates.

Communication

We use both Teams and email for communication. I send emails at all hours but don’t expect the same back, unless it’s in your best interests to reply (e.g. imminent paper submission deadline). However, if you have a problem and need help, you are always welcome to contact me, including by mobile.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once a month

In year 1 of PhD study

At least once a fortnight

In year 2 of PhD study

At least once a fortnight

In year 3 of PhD study

At least once a month

These meetings will be a mixture of face to face, via video chat or telephone, and I am usually contactable for an instant response 3 or 4 days a week.

Working Pattern

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team. (I prefer you generally to be in core hours but it is not obligatory).

Notice Period for Feedback

I need at least 2 weeks' notice to provide feedback on written work of up to 5000 words (but can cope with less in emergencies).

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

The importance of phospholipids in the function of the mechanosensory PIEZO 1

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

The importance of phospholipids in the function of the mechanosensory PIEZO 1

Secondary Supervisor(s): Dr Naomi Pollock, Dr Benjamin Lane

University of Registration: Aston University

BBSRC Research Themes: Understanding the Rules of Life (Structural Biology)

Project Outline

PIEZO1 is the largest and most complex mechanosensitive ion channel known and mediates responses to a variety of mechanical signals such as shear stress, stretch and force. It is widely expressed and functional throughout the human body; gain- or loss-of-function PIEZO mutations are linked to a wide variety of medical conditions and diseases, several of which are life-threatening, illustrating the physiological importance of these proteins. Following the Nobel Prize for PIEZO research in Physiology or Medicine in 2021, this continues to be a hot topic, with various unanswered mechanistic questions.

Structurally, PIEZO1 exists in a trimeric form with a curved transmembrane (TM) region that can flatten in response to mechanical stimuli such as bilayer stretching, allowing ion channel opening and downstream signalling. One of the key questions in the field is how a single protein complex can respond to diverse stimuli with different sensitivities and transduce them through downstream signalling to different cellular behaviours. A contributing factor is likely to be the close association of specific lipids in the surrounding membrane, which can act as regulators or determine the biophysical properties of the bilayer (thickness, fluidity, tension) that influence its conformational changes. As yet there have been few practical studies on lipid-human PIEZO1 interactions. This information is crucial to understanding PIEZO1 regulation, computational modelling of its function and ultimately exploiting it as a therapeutic target for specific pathological conditions.

Aim and Objectives

The aim of this project is therefore to identify the preferred interactions of PIEZO1 with membrane phospholipids in different mammalian cell types to understand their contribution to mechano-signalling outcomes.

The specific objectives are to:

1. Establish co-polymer extraction methods using styrene maleic acid and other copolymers (DIBMA or amphipols) for native huPIEZO1 from human erythrocytes and HUVECs, to form SMALPs. Extraction will be tested by SDS-PAGE and western blotting. Preliminary data suggest that SMA2000 is able to extract PIEZO1 effectively.

2. Establish transient transfection of mammalian cells (HEK293 cells, Cos-7 fibroblasts) with PIEZO1 containing GST/Flag constructs for expression and purification of the protein. PIEZO1 expression will be confirmed by fluorescent microscopy of cells and western blotting of membrane preparations.

3. Use pull-downs with an anti-huPIEZO1 antibody or GSH-resin to purify the PIEZO-containing SMALPs from either native expression in erythrocytes or overexpression in HEK-293 or Cos-7 cells.

4. Analyse the membrane lipids and phospholipids surrounding huPIEZO1 in membrane discs extracted with various polymers from different cell types, using liquid chromatography tandem mass spectrometry.

5. Carry out in-depth lipidomics data analysis using to characterize the preferred membrane phospholipid environment of PIEZO1 in cells with specific mechanosensor responses.

References

Ligand-induced conformational changes in a SMALP-encapsulated GPCR. Routledge SJ, Jamshad M, Little HA, Lin YP, Simms J, Thakker A, Spickett CM, Bill RM, Dafforn TR, Poyner DR, Wheatley M. Biochim Biophys Acta Biomembr. 2020 Jun 1;1862(6):183235. doi: 10.1016/j.bbamem.2020.183235.
Analysis of SMALP co-extracted phospholipids shows distinct membrane environments for three classes of bacterial membrane protein. (2019) Teo ACK, Lee SC, Pollock NL, Stroud Z, Hall S, Thakker A, Pitt AR, Dafforn TR, Spickett CM, Roper DI. Sci Rep. 12;9(1):1813. doi: 10.1038/s41598-018-37962-0.

Co-supervisor on a project with Dr Benjamin Lane.

Previous Projects (2024-25)

Primary supervisor for:

Understanding the redox regulation of the tumour suppressor and cell signalling protein PTEN

Co-supervisor on a project with Dr Rebecca Jones.

Previous Projects (2023-24)

Primary supervisor for:

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