Information about available funded PhD Positions
(College of Science and Engineering)
Visualizing mitochondrial dysfunction in human neurons and cardiomyocytes with oxidative stress reporter iPSC lines
Applications accepted up to Thursday 31st March, 2022, 5pm
1st Supervisor: Prof Tilo Kunath (University of Edinburgh)
Other Supervisors: Prof Qingfeng Yan (Zhejiang University)
About the Project
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.
- 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.
- 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.
- 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.
- 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.
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.
This is a collaborative project between the University of Edinburgh and Zhejiang University.
An MSc degree is not a requirement.
Using the link below, the “Institution Website” button will take you to our online Application Checklist. From here you can formally apply online via EUCLID.
Martin Lee Doctoral Scholarship Programme
Build your expertise in stem cell and regenerative medicine
The Martin Lee Doctoral Scholarship Programme in Stem Cell and Regenerative Medicine aspires to educate the next generation of leaders and influencers in regenerative medicine. Regenerative medicine seeks to replace or regenerate damaged or diseased cells or organs to restore normal function. This 4-year PhD programme will deliver bespoke, cross-disciplinary training to equip graduates with the skills to drive regenerative medicines potential to advance human health.
Students will receive supervision and mentoring from world-renowned experts in stem cell research, regenerative medicine, inflammation research and tissue repair. The programme is hosted at IRR on the site of the Edinburgh bioQuarter, a vibrant environment where scientists and clinicians are working closely together to translate their exciting research into the clinic.
The Martin Lee Doctoral Scholarship programme is a 4-year programme
Martin Lee Doctoral Scholars have 4 years for their PhD training, research and writing. The programme is structured as '1+3' years, as follows:
- In year 1, students complete two research rotations (~12 weeks each), after which they will be involved in developing a detailed research proposal for their chosen topic
- In years 2-4, students will undertake their PhD research project, allowing ample time for the writing of their thesis and any associated manuscripts.
This recruitment round for Martin Lee Doctoral Scholarships is open only to those ordinarily resident in Hong Kong.
Martin Lee Doctoral Scholarships are awarded competitively. Applicants need to submit their application via an online application form which can be accessed via the link below.
Closing date for applications for this recruitment round is Thursday 21st April 2022, 12 noon (GMT).
MSc By Research: Regenerative Medicine and Tissue Repair Programme
Our MSc by Research in Regenerative Medicine and Tissue Repair is a one-year, full-time, on-campus Masters programme structured around two laboratory-based research projects and a research proposal writing component.
The programme is based at the Centre for Regenerative Medicine (CRM), a purpose-built research environment at the heart of Edinburgh BioQuarter, with a track record in training over 180 postgraduate students.
This MSc by Research is designed to prepare you for a research career in academia or industry, whether you have recently completed an undergraduate degree or are a professional who wants to pursue a career in research. You will gain valuable transferable skills that will be beneficial in a wide range of professions.
Self Funded Applicants
We encourage inquiries and applications from self-funded basic and clinical scientists and from candidates who intend to apply for external funding all year round.
Instructions on how to apply as a self funded student
Studentships can include:
- Stipend for 3 or 4 years
- Tuition Fees
- Research Training Costs
- Conference Travel Allowance
Please contact relevant principal investigators informally to discuss potential projects and visit our funding opportunities page.