Understanding cell-type specific mtDNA generation and maintenance in the human central nervous system

About the Project

The PhD project offers an exciting opportunity to pioneer cutting-edge research into mitochondrial DNA (mtDNA) heteroplasmy in the human brain—a rapidly emerging field with major implications for understanding and treating neurological diseases.

Why do different cell types in the central nervous system (CNS)—such as neurons, astrocytes, microglia, and oligodendrocytes—show strikingly unique patterns of mtDNA heteroplasmy, even though they share the same nuclear genome and environment? Recent single-cell studies and organoid models reveal these cell-type-specific differences, but the underlying mechanisms (stochastic drift versus active selection driven for example) remain largely unknown. This project will resolve that mystery.

Even more impactfully, could these patterns unlock non-invasive biomarkers of neurological disease or injury? Circulating cell-free mtDNA (ccf-mtDNA) is elevated in many neurological disorders, reflecting neurodegeneration and inflammation. By linking brain cell-type-specific heteroplasmy to ccf-mtDNA profiles, this work could reveal disease-specific shedding signatures—potentially transforming diagnostics for multiple neurological disorders.

You will use state-of-the-art techniques developed in our labs:

• Year 1: Lead single-cell/FACS-sorted mtDNA sequencing from human brain tissue (surgical, postmortem, frozen) to profile heteroplasmy across CNS populations and trace ccf-mtDNA origins.
• Year 2: Apply in situ mtDNA sequencing for spatial mapping in diseased tissue, correlating variants with pathology and cell identity.
• Years 2–3: Model selection dynamics using patient-derived iPSCs differentiated into CNS lineages (neurons, astrocytes, microglia), tracking heteroplasmy shifts to uncover causal mechanisms.

This interdisciplinary project combines clinical neurology, single-cell omics, mitochondrial genomics, and neuropathology. You'll work in Newcastle's vibrant research environment, supervised by Dr. Michael Keogh (expert in brain tissue isolation and neurogenetics), Professor Gavin Hudson (mitochondrial genomics leader), and Dr. Christopher Morris (Newcastle Brain Tissue Resource Director), gaining hands-on training in advanced methods, bioinformatics, and translational research.

Ideal for candidates passionate about neuroscience, genetics, or biomedicine who want to generate high-impact data, publish in top journals, and contribute to biomarker/therapy development. Join us to shape the future of mitochondrial neuroscience!

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.