PhD Opportunities

Information about available funded PhD Positions

(College of Science and Engineering)

Engineering the embryonic haematopoietic stem cell (HSC) niche in vitro

Applications accepted up to Friday 31st March, 5pm

1st Supervisor: P rof Alexander Medvinsky (University of Edinburgh)

Other Supervisors: Dr Guillaume Blin (University of Edinburgh)

About the Project

Background. Bone marrow HSCs are broadly used for clinical transplantations, but the need for donors outstrips supply. Pluripotent human ES/iPS cells could be a great alternative source of HSCs to meet demands. During embryo development, HSCs emerge in the dorsal aorta within the aorta-honad-mesonephros (AGM) region through the process called endothelial-to-haematopoietic transition (EHT). However, molecular mechanisms underlying EHT are poorly understood. Although the cultured mouse AGM region can recapitulate HSC development, multiple attempts to derive HSCs from ES/iPS cells without genetic manipulations fail.

Hypothesis and goals. During embryogenesis, organs and tissues show a great degree of self-organisation. It is becoming increasingly evident that tissue patterning and cell specification can be guided by geometric physical constraints of the substrate. Spatial dorso-ventral polarisation of secreted molecules in the AGM region also play a role in HSC development. We propose that a combination of geometrical constraints and spatially polarised signalling will enable functional AGM organoids to be generated in vitro. The main goal of the project is to generate an efficient in vitro platform for investigating effects of spatial constraints and molecular polarisation on reconstruction of the human AGM region.

Approaches and methodology. The student will generate a dual fluorescent reporter human ES cells using CrispR/CAS9 system to facilitate efficient screening for conditions supporting AGM organoid formation and EHT. Highly controlled geometrically constrained supports for cultured cells and polarised signalling will be established using the cutting-edge micropatterning machine (Primo, Alveole). Cell specification and formation of AGM organoids will be explored using fluorescent microscopy, flow cytometry and gene expression analysis with support of bioinformatics. Blood cells generated in the system will be tested functionally by transplantation into immunocompromised NSG mice.

Training. The student will receive interdisciplinary training in areas of microfabrication, developmental biology, experimental haematology, gene editing, flow cytometry, confocal microscopy and bioinformatics.

Impact. Pluripotent hES/iPS cells hold great hope for regenerative medicine. These are potentially a valuable source of HSCs that could overcome the shortage of donors and enhance safety of transplantations. However, to date HSC derivation from cultured hES cells remains a challenge. This project has a strong translational aspect and can open up opportunities to develop new protocols for directed differentiation of bona fide HSCs for clinical applications.

Environment. You will be working in a highly collaborative environment of Medvinsky’s lab. We were the first who discovered the central role of AGM region in HSC development and demonstrated that the AGM region can autonomously generate HSCs in culture. We have a strong record studying both the mouse and human AGM region at cellular and molecular levels, including spatial transcriptomics analyses. This project will be conducted in collaboration with Dr. Guillaume Blin, Quantitative Biology of Pattern Formation group.

Funding Notes

This 3.5 year PhD project is funded by EPSRC Doctoral Training Partnership This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate (£17,668 annually in 2022) and UK level tuition fees. The fee difference will be covered by the University of Edinburgh for successful international applicants, however any Visa or Health Insurance costs are not covered. UKRI eligibility guidance: Terms and Conditions: View Website International/EU: View Website

References

McGarvey, et al (2017). A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation. J Exp Med 214, 3731-3751.
Ivanovs, A., et al. (2017). Human haematopoietic stem cell development: from the embryo to the dish. Development 144, 2323-2337.
Crosse, E. et al (2020). Multi-layered spatial transcriptomics identify secretory factors promoting human hematopoietic stem cell development. Cell Stem Cell 27, 822-839.

Applications

The School of Biological Sciences is committed to Equality & Diversity: https://www.ed.ac.uk/biology/equality-and-diversity

The “Apply Now” button on this page will take you to our Online Application checklist. Please carefully complete each step and download the checklist which will provide a list of funding options and guide you through the application process. From here you can formally apply online. Application for admission to the University of Edinburgh.

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(College of Science and Engineering)

Engineering rejuvenation factors to reverse aging

Applications accepted up to Friday 31st March, 5pm

1st Supervisor: Prof Abdenour Soufi (University of Edinburgh)

Other Supervisors: Prof Keisuke Kaji (University of Edinburgh)

About the Project

Aging is a major challenge to our society due to the general decline in fitness and function, as well as the associated risk of disease. Strikingly, recent advances in cellular reprogramming have demonstrated the potential to reverse the process of aging through the transient expression of four transcription factors (TFs) known as Oct4, Sox2, Klf4 and Myc (OSKM). Such partial cellular reprogramming has been shown to rejuvenate multiple features of ageing including the epigenetic clock without the loss of cellular identity, which is often the result of cellular reprogramming. However, using OSKM in human rejuvenation increases the risk of tumours due the unwanted cell fate conversion and dedifferentiation. The main goal of this PhD project is to engineer synthetic rejuvenation factors by extracting defined molecular features of OSKM and eliminating unnecessary side activities.

The student will be directly involved in experimental design, data collection and analysis, documenting and communicating the research findings through written reports and oral presentation. The student will be supervised and supported by the PhD supervisors and other senior members of the Soufi Lab. The student will be assigned an independent research committee that asses the guide the student throughout this PhD project.

The student will be trained in wide range of techniques:

- High-throughput mutation analysis.

- Next-generation sequencing (NGS) based techniques such ChIP-seq, RNA-seq, ATAC-seq and DNA Methylation profiling.

- Various bioinformatic analysis and AI algorithms.

- Full and partial Reprogramming to iPSCs.

- Differentiation assays and various tissue culture techniques to maintain iPSCs and ESCs.

- Various molecular and cellular biology methods.

The student will also benefit from the diverse training programs and workshops offered by the University of Edinburgh and the Institute of Tissue Regeneration and Repair (IRR) offered to PhD students. The student will be part of a vibrant and supportive scientific community at IRR and university of Edinburgh.

Funding Notes

References

Gill, D., Parry, A., Santos, F., Okkenhaug, H., Todd, C. D., Hernando-Herraez, I., Stubbs, T. M., Milagre, I., & Reik, W. (2022). Multi-omic rejuvenation of human cells by maturation phase transient reprogramming. eLife, 11, e71624.
Roberts, G. A., Ozkan, B., Gachulincová, I., O'Dwyer, M. R., Hall-Ponsele, E., Saxena, M., Robinson, P. J., & Soufi, A. (2021). Dissecting OCT4 defines the role of nucleosome binding in pluripotency. Nature cell biology, 23(8), 834–845.
Abad, M., Mosteiro, L., Pantoja, C., Cañamero, M., Rayon, T., Ors, I., Graña, O., Megías, D., Domínguez, O., Martínez, D., Manzanares, M., Ortega, S., & Serrano, M. (2013). Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature, 502(7471), 340–345.

Applications

The School of Biological Sciences is committed to Equality & Diversity: https://www.ed.ac.uk/biology/equality-and-diversity

Apply Now

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 Integrated 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:

Year one - Foundation training and research rotation projects (180 credits)

Students will receive training in good research practice, scientific reasoning, research ethics and the critical assessment of research papers, and attend seminars and journal clubs. Students carry out two research projects (~15 weeks) and will disseminate their findings through oral presentations and a dissertation (max 10,000 words; 60 credits each).

After the rotation projects, students develop and submit a detailed PhD research proposal for their chosen topic, under the guidance of their supervisor (60 credits). Projects will span the breadth of research areas at IRR.

Years two to four - PhD research project (540 credits)

Students undertake their PhD project, allowing time for research and the writing of their thesis and any associated manuscripts.

Eligibility

Please note that recruitment is currently closed. It may open later this year for 2023/2024 intake. This website will be updated accordingly.

Martin Lee Doctoral Scholarship Programme Application

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.

MSc By Research: Regenerative Medicine and Tissue Repair website

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.

Information and contacts for principal investigators

PhD funding and finance

Further information about MRC Studentships

This article was published on 9 Oct, 2020