Dr James Coverdale

Supervisor Details

Contact Details

School of Pharmacy, University of Birmingham

Scientific Background

Research Interests

Dr Coverdale's research focuses on the role of metals in medicine, and the development of new experimental techniques. James has a specific interest in how metal dyshomeostasis can contribute to various pathological states, and how metal-based therapies can provide new opportunities for the treatment of diseases.

Supervision Style

In three words or phrases: goal-driven, student-oriented, inclusive.

Provision of Training

I prefer to take responsibility for your technical training at first, leading to more independence later.

Progression Monitoring and Management

I expect you to take ownership of your progression but come to me when you need help troubleshooting. I am here for advice and guidance to help you reach the goals we set together.

Communication

Our team has a MS Teams group chat in which we regularly communicate. Whilst I expect you to keep up with my / team communications during core work hours, I encourage students to maintain a healthy work/life balance and discourage out-of-hours communication where avoidable.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per fortnight

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per fortnight

In year 3 of PhD study

At least once per fortnight

Meetings will mainly be face to face, and I am usually contactable for an instant response 3 or 4 days a week.

Working Pattern

The timing of work in my lab is completely flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time.

Notice Period for Feedback

I need at least 1 week's notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Modulation of endogenous metal ion homeostasis by redox-targeting pharmaceuticals: a bioanalytical and multi-omic study

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).

Modulation of endogenous metal ion homeostasis by redox-targeting pharmaceuticals: a bioanalytical and multi-omic study

Secondary Supervisor(s): Dr Hannah Bridgewater

University of Registration: University of Birmingham

BBSRC Research Themes: Integrated Understanding of Health (Pharmaceuticals)

Project Outline

Metals are essential to life and strict regulation of metal homeostasis (modulation of influx/efflux, compartmentalisation, and speciation) is critical to achieve correct cellular function. For example, Fe plays a role regulated in cell death, while Fe dyshomeostasis is closely related to the occurrence and development of tumours.[1]

Novel therapeutics are under development which purposely modulate cellular redox to achieve anticancer potency, involving the generating reactive oxygen species (ROS) and/or targeting mitochondrial function.[2] Cellular redox balance is intricately linked to endogenous metal biology; for example, Cu and Zn are co-factors of Cu/Zn superoxide dismutase, an enzyme which detoxifies ROS generated by the mitochondrial electron transport chain. Cu also has an indirect role on mitochondrial function, related to mitochondrial Fe uptake since Cu is a co-factor of ferroxidases.[3] In fact, Cu chelators are currently being evaluated for anticancer applications.[4]It is thus clear that there are multiple links between the mode of action of metallodrugs and the metabolism of endogenous metals, but despite this, little consideration has been given as to how endogenous metal ion homeostasis is impacted by therapeutics.

Objectives

This project will explore the impact of redox-targeting anticancer drugs on endogenous metal ion (e.g., Fe, Cu, Zn) homeostasis. Specifically, the project will develop new and existing bioanalytical and metalloproteomic techniques to quantify changes in intracellular metal ion concentrations, distributions, and speciation. Additionally, key gene regulators of intracellular metal ions will be identified and the impact of xenobiotic anticancer drugs on their expression and localisation within the cell or tumour will be investigated.

Methods

This highly interdisciplinary project will provide the student with laboratory training in multi-omic approaches in biological research, including CRISPR/CAS9, metalloproteomic analysis (metal ion speciation) and whole-genome sequencing. This project will investigate the time-dependent and concentration-dependent response of intracellular endogenous metal ions to redox-targeting therapeutics in the early stages of the drug development pipeline. In Year 1, this will be achieved using elemental analysis (ICP-MS) building upon previous work the research teams during previous collaborative projects,[5] and will then advance to evaluate metallome impact at the single-cell level using single-cell ICP-MS (SC-ICP-MS), an emerging technology pioneered by the Coverdale Group (University of Birmingham).[6-9]

In Year 2, the student will undertake complementary transcriptomic/genomic/proteomic investigations of the biological impact of metal ion modulation on key gene regulators; investigating differential gene expression and changes in protein localisation. The Bridgewater Group (University of Warwick) will provide expertise in cell biology and -omics approaches. This unique interdisciplinary project will enable the mapping of single-cell RNAseq to complement single cell ICP.

In Year 3, the student will apply new knowledge of metallomic and genomic impacts to generate cell models modulating the expression of a couple of key genes using CRISPR-Cas9 techniques. This will unite the findings from Year 1/2 and confirm gene functions in xenobiotic metal distribution, concentrations and speciation.

References

[1] Q. Guo, et al., Frontiers in Oncology, 2021, 11.

[2] Anthony et al., Chemical Science, 2020, 11, 12888-12917.

[3] L. M. Ruiz, et al., Frontiers in Molecular Biosciences, 2021, 8.

[4] D. Ramchandani et al., Nature Communications, 2021, 12, 7311.

[5] Coverdale et al., Metallomics, 2019, 11, 1805.

[6] Coverdale et al., Chemical Communications, 2022, 58, 7384-7387.

[7] Coverdale et al., Nature Chemistry, 2018, 10, 347–354.

[8] Blindauer et al., Journal of Proteomics, 2022, 263, 104615.

[9] Blindauer et al., Nature Chemical Biology, 2022, 18, 869–8.