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Visualizing mitochondrial dysfunction in human neurons and cardiomyocytes with oxidative stress reporter iPSC lines

   School of Biological Sciences

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  Dr T Kunath  No more applications being accepted  Self-Funded PhD Students Only

About the Project

*The difference between international and UK fee rate will be covered by the University of Edinburgh for successful candidates*

Supervisors: Tilo Kunath, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh ([Email Address Removed]) and Qingfeng Yan, Institute of Genetics and Regenerative Biology, Zhejiang University ([Email Address Removed])

An MSc degree is not a requirement.

Project details

Mitochondrial dysfunction is a significant driver of diverse human diseases, including Parkinson’s disease (PD) and cardiovascular disease (CVD). The advent of induced pluripotent stem cell (iPSC) technology has provided exceptional opportunities to study diseases in a dish. Protocols to produce dopaminergic neurons and cardiomyocytes for disease modeling from human iPSCs are now very efficient and well-established in the Kunath and Yan labs, respectively (Chen et al, 2019; Zhang et al, 2016).

 This project consists of three parts. 1. Generation of an allelic series of CRISPR-engineered iPSC lines with fluorescent reporters of oxidative stress (roGFP) within mitochondria (Cannon & Remington, 2006). 2. Live-imaging of roGFP-iPSC-derived dopaminergic neurons and cardiomyocytes under conditions of low and high oxidative stress. 3. Investigation of PD and CVD disease models with roGFP-iPSC lines.

1.   A healthy control human iPSC will be targeted at a known locus (eg. AAVS1) with a defined collection of targeting vectors that encompass selected next-generation redox-sensitive GFP (roGFP) constructs fused with mitochondrial targeting sequences (MTS). Upon live-imaging characterization, the most optimal reporter cell lines will be used for the next stages of the project.

2.   Differentiation of roGFP-iPSCs into dopaminergic neurons (Kunath lab) and cardiomyocytes (Yan lab) will be performed and cells will undergo various treatments to induce generic oxidative stress, and imaged for signs of mitochondrial dysfunction and oxidative stress.

3.   roGFP-iPSC-derived dopaminergic neurons and cardiomyocytes with be induced to acquired disease-like phenotypes by treatment with MPP+ for dopaminergic neurons and hypoxia for cardiomyocytes. The kinetics and dynamics of mitochondrial oxidative stress will be dissected under these disease model conditions.

PI Websites:

Tilo Kunath

Qingfeng Yan

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Funding Notes

The difference between international and UK fee rate will be covered by the University of Edinburgh for successful candidates. Successful candidates will be required to provide evidence of funding to cover the UK fee rate, plus living expenses of approximately £15k per year.


Cannon MB, Remington SJ. (2006) Re-engineering redox-sensitive green fluorescent protein for improved response rate. Protein Sci.15(1):45-57. doi: 10.1110/ps.051734306.
Chen Y, Dolt KS, Kriek M, Baker T, Downey P, Drummond NJ, Canham MA, Natalwala A, Rosser S, Kunath T. (2019) Engineering synucleinopathy-resistant human dopaminergic neurons by CRISPR-mediated deletion of the SNCA gene. Eur J Neurosci. 49(4):510-524. doi: 10.1111/ejn.14286.
Xuan Zhang, Shishi Li, Wei Yang, Huaye Pan, Dajiang Qin, Xufen Zhu, Qingfeng Yan (2016) Mitochondrial disease-specific induced pluripotent stem cell models: Generation and Characterization, Methods in Molecular Biology, 1353: 323–342. DOI 10.1007/7651_2014_195.

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