Centre for Regenerative Medicine

PhD Opportunities

Information about available funded PhD Positions

(College of Science and Engineering) 

EASTBIO In vitro modelling of the embryonic haematopoietic stem cell niche  

Applications accepted up to Monday 5th December 2022, 5pm 

1st Supervisor: Prof Alexander Medvinsky (University of Edinburgh)

Other Supervisors:  Dr Guillaume Blin (University of Edinburgh)

About the Project

Background. The first haematopoietic stem cells (HSCs) emerge in the embryonic aorta-gonad-mesonephros (AGM) region through a process called endothelial-to-haematopoietic transition (EHT). We previously showed that secreted molecules in the AGM region are spatially polarized and some of them support HSC development (2,3). However, the full impact of this complex polarized microenvironment on haematopoietic development remains unclear. We propose that spatial intersections of secreted factors define the efficacy and specifics of EHT within the AGM region.

Objectives. We will investigate how spatial patterning of secreted molecules in the AGM region impacts on haematopoietic development (EHT). Using human ES cells, we will model the HSC niche by spatially patterned combinatorial expression of secreted molecules. Results will be obtained and analysed using fluorescent reporters, single cell RNAseq, flow cytometry and computer modelling. In the longer term, these analyses will facilitate generation of human HSCs for clinical needs.

Techniques and skills to be employed/ acquired. This project will be carried out in a highly collaborative environment. The student will learn cutting-edge and multidisciplinary methods including human ES cell differentiation, live imaging, micropatterning, confocal microscopy, flow cytometry, CRISPR/Cas9 gene editing; gene expression profiling (RNAseq) and bioinformatics. 

References

  1. Ivanovs, A., Rybtsov, S., Ng, E.S., Stanley, E.G., Elefanty, A.G., and Medvinsky, A. (2017). Human haematopoietic stem cell development: from the embryo to the dish. Development 144, 2323-2337.
  2. Crosse, et al (2020). Multi-layered spatial transcriptomics identify secretory factors promoting human hematopoietic stem cell development. Cell Stem Cell 27, 822-839.
  3. Souilhol, et al (2016) “Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells. Nat. Commun. 7, 10784.

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership View Website 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

Applications

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

The Apply Now link will take you to our online Application Checklist. From here you can formally apply online. This checklist also provides a link to EASTBIO - how to apply web page. You must follow the Application Checklist and EASTBIO guidance carefully, in particular ensuring you complete all the EASTBIO requirements, and use /upload relevant EASTBIO forms to your online application.

Apply Now

 

(College of Science and Engineering) 

EASTBIO How do patterns of cell fate scale with tissue size? A forward engineering approach 

Applications accepted up to Monday 5th December 2022, 5pm 

1st Supervisor: Dr Guillaume Blin (University of Edinburgh)

Other Supervisors:  Dr Mattias Malaguti (University of Edinburgh)

About the Project

Main Question:

During development, homeostasis and tissue regeneration, coordinated cell fate decisions ensure that a balanced proportion of tissue progenitors are specified in the correct place and at the correct time while accommodating for changes in tissue and geometry size. How do stem cells achieve precise patterning of cell fates? How do patterns resist perturbations and how do they scale with tissue size?

 Objectives:

To address these fundamental questions, we will employ a forward engineering approach: Instead of performing perturbation experiments in embryos to pick apart the underlying mechanisms of development, we will use a bottom-up approach where we will engineer simple behaviors (or rules) into cell lines which do not normally form patterns. We will confine the cells onto micropatterns of defined size and geometries (Blin, 2021) and test whether the rules we engineer elicit scalable patterning.

The candidate may explore two main mechanisms that have emerged from preliminary results: 1) a sorting mechanism where weighted random fate allocation in the population is followed by directional movements and 2) a mechanotransduction mechanism where tissue-level tension elicits cell fate diversification in-situ in a spatially organised manner.

The candidate will explore and validate these mechanisms experimentally and theoretically using a combination of mammalian synthetic biology (Davies, 2017) and agent-based modelling (Ghaffarizadeh et al., 2018).

Impact:

This project will validate fundamental principles of patterning uncovered through classical approaches, identify novel parsimonious patterning designs not selected by evolution and test quantitatively the robustness and evolvability of these designs. The candidate will also develop novel synthetic pathways such as a synthetic mechanotransducer that will be broadly applicable in other contexts.

 Training:

This project will be carried out in a highly collaborative environment. The student will learn wet-lab methods including a repertoire of mammalian synthetic biology techniques, microfabrication techniques, live and high content imaging and flow cytometry, as well as theoretical tools including image analysis software, data visualisation with python and multi-scale agent-based modelling. Our lab also adopts and promote FAIR principles which the candidate will be introduced to.

Training will be enabled by a multidisciplinary team of supervisors and collaborators dedicated to nurture the candidate’s aspiration to become a skilled researcher who can work at the interface of several disciplines.

https://www.ed.ac.uk/regenerative-medicine/research/guillaume-blin

https://www.ed.ac.uk/profile/mattias-malaguti

References

  1. Blin, G. (2021). Quantitative developmental biology in vitro using micropatterning. Development 148,.
  2. Davies, J. (2017). Using synthetic biology to explore principles of development. Development 144, 1146–1158.
  3. Ghaffarizadeh, A., Heiland, R., Friedman, S. H., Mumenthaler, S. M. and Macklin, P. (2018). PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems. PLOS Computational Biology 14, e1005991.

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership View Website 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

Applications

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

The Apply Now link will take you to our online Application Checklist. From here you can formally apply online. This checklist also provides a link to EASTBIO - how to apply web page. You must follow the Application Checklist and EASTBIO guidance carefully, in particular ensuring you complete all the EASTBIO requirements, and use /upload relevant EASTBIO forms to your online application.

Apply Now

 

 

(College of Medicine and Veterinary Medicine) 

EASTBIO Mathematical modelling of multicellular circuits giving rise to dynamic tissue states in liver disease

Applications accepted up to Monday 5th December 2022, 5pm 

1st Supervisor: Dr Linus Schumacher (University of Edinburgh)

Other Supervisors:  Dr Jochen Kursawe (University St Andrews) and Prof Jonathan Fallowfield (University of Edinburgh)

About the Project

Non-alcoholic fatty liver disease is the commonest cause of liver disease, affecting 1 in 4 people worldwide. Only a proportion of patients with a fatty liver go on to develop serious liver problems but, crucially, we don’t understand why some NAFLD patients progress and others don’t. This interdisciplinary project will investigate the multicellular mechanisms underlying NAFLD using mathematical models. We aim to provide a novel theoretical perspective on NAFLD progression as a slowly fluctuating, stochastic dynamical system. We hypothesise that the variable progression of NAFLD can be explained by complex interactions between different cell states (‘cell circuits’) and different sources of variability (genetic and environmental factors, molecular/cellular variability, spatial heterogeneity). To test this idea, you will develop a theory of stochastic cell circuits to explain variability in disease progression and to integrate multiple data sources. The mathematical modelling will provide a theoretical foundation from which to understand variability and speed of NAFLD progression. From the inferred mechanisms of cell interactions, we may be able to predict which stage-specific interventions (modulations of individual cell activities or their interactions) are optimal to halt or revert progression. There is the possibility to test model predictions with biomedical collaborators in the form of drug combinations in in vitro models or to validate them on medical cohort data. This would allow us to refine the mechanisms in the mathematical model further, in an iterative predict-test-refine cycle between theory and experiments.

The project will be based in the group of Linus Schumacher at the Centre for Regenerative Medicine in Edinburgh, and co-supervised by Jochen Kursawe (Mathematics, St. Andrews) and Jonathan Fallowfield (Centre for Inflammation Research, Edinburgh). The Schumacher group has extensive experience in building mathematical models and collaboration with experimental groups, and the Centre for Regenerative Medicine provides a stimulating research environment and training opportunities for PhD students. Dr Kursawe will contribute expertise in stochastic modelling and modelling of cell states. Prof Fallowfield will provide translational research expertise in NAFLD and fibrosis biology, and access to the SteatoSITE NAFLD Data Commons. There is further opportunity to interact with the systems biology and mathematical biology communities in Edinburgh and St. Andrews.

Funding information and application procedures:

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP) http://www.eastscotbiodtp.ac.uk/how-apply-0 .

This opportunity is open to UK and international students and provides funding to cover stipend and UK level tuition fees.  The University of Edinburgh will cover the difference between home and international fees meaning that the EASTBIO DTP will offer fully-funded studentships to all appointees.  However there is a cap on the number of international students the DTP can recruit.  It is therefore important for us to know from the outset which fees status category applicants will fall under when formally applying for entry to our university.

Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.

EASTBIO Application and Reference Forms can be downloaded via http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to crm-training@ed.ac.uk

You should also ensure that two references have been sent to crm-training@ed.ac.uk by the deadline using the EASTBIO Reference Form.

 

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

Contact us for more information