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PhD opportunities

University funded PhD positions are advertised below. Please use the links on each project to apply.

BBSRC EASTBIO DTP: Modelling cell state transitions in differentiating embryonic stem cells

Deadline for applications - Wednesday 5th December 2018

1st Supervisor: Prof Val Wilson
2nd Supervisor: Dr Linus Schumacher

Project Description

Biologists increasingly use the concept of cell states to classify cellular behaviour in development, regeneration, and cancer. This is driven in part by an abundance of data comprising snapshots of cell populations at single-cell resolution. Yet quantitative predictive models of cell states and their regulatory networks remain lacking. Such models are required for an integrative mechanistic understanding of the structure of cell populations and their plasticity, and could help, for example, optimise differentiation protocols in vitro. 

This project will investigate early cell fate decisions in stem cell populations resembling early embryonic progenitors, using a combination of quantitative analysis of lineage marker expression and data-driven mathematical modelling of cell state transitions. Models will be calibrated against population and single-cell data using a Bayesian inference approach to quantify the cell state transition rates and their uncertainties, and how these change under different culturing conditions. 

The lab of VW has pioneered the culture of lineage-biased pluripotent cells. LS’s research group focuses on the computational modelling of cell populations and their self-regulation, and how single-cell data can be used to inform such models. LS has developed a preliminary modelling approach (unpublished, similar in its approach to [2]) and Bayesian inference pipeline (see [3] for a review) to VW’s existing data [1]. 

The student will receive training in relevant ‘wet lab’ techniques, such as cell culture and microscopy/image analysis, while working with existing preliminary data and developing the computational tools for modelling and analysis, such as Markov models of cell state transitions and parameter inference. Utilizing this skills development the student will experimentally test predictions from the model in the second half of the PhD. Depending on the student’s skills and interests, the project can then be taken into several further directions, such as working with human cell lines, scaling the method to work with transcriptomic data, or exploring different theories of cell state. 

LS and VW will have an active supervisory role and hold regular progress meetings with the student. Training in professional and research skills will be tailored to the individual student’s background and training needs. The student’s critical understanding of primary data and research literature will be advanced through regular group meetings and journal clubs at the Centre for Regenerative Medicine. The student will also have the opportunity to engage with the mathematical and systems biology research community at other departments in Edinburgh. 

This project is a great opportunity for students with a background in mathematics, statistics, physics, computer science, engineering, or similar, or from a biological background with existing skills and interests in computer programming. The student will benefit from integration in an active biomedical research environment at the Centre for Regenerative Medicine and interaction with a cross-institutional network of collaborators. 

Funding Notes

To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement. 

Other Information

All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree

Subject Areas

Bioinformatics, Biomedical Engineering, Biophysics, Cell Biology / Development, Molecular Biology

Apply Now

Download application and reference forms via: https://www.ed.ac.uk/roslin/postgraduate/bbsrc-eastbio-dtp 

Completed application form along with your curriculum vitae should be sent to our PGR student team at RDSVS.PGR.Admin@ed.ac.uk 

Please send the reference request form to two referees. Completed forms for University of Edinburgh College of Medicine and Veterinary Medicine project should be returned to RDSVS.PGR.Admin@ed.ac.uk by the closing date: 5th December 2018. 

It is your responsibility to ensure that references are provided by the specified deadline. 

Modelling stem cell population dynamics: from cell interaction networks to tissue regeneration

Deadline for applications - Monday 10th December 2018

1st Supervisor: Dr Linus Schumacher
2nd Supervisor: tbc

Background

Tissue regeneration is an emergent phenomenon at the scale of cell populations. The requirement for robust tissue homeostasis without over-proliferation poses a constraint on the possible cellular dynamics to build and maintain tissues, as only some sets of microscopic mechanisms, or "rules", will enable regeneration after injury. In healthy tissues, cell populations also have to self-regulate so as not to over-proliferate and grow in an unregulated, or malignant, manner. Despite a rich history of insights from developmental biology, quantitative & predictive understanding of regeneration and repair remains elusive. Our group uses mathematical and computational modelling to predict outcomes of hypothesised regulatory mechanisms in development and regeneration. By developing theoretical models we also come up with new perspectives on how to interrogate experimental data. We work closely with experimental collaborators with the long-term aim to formulate principles that apply to multiple biological systems, gain insight into misregulation in disease, and inform improvements to regenerative therapy.

About the project

We are looking for an ambitious and motivated postgraduate candidate to join the new computational biology group, led by Linus Schumacher, at the MRC Centre for Regenerative Medicine in Edinburgh. The group is using expertise in mathematical modelling of cellular processes in development [1,2] and collective behaviour in biological systems [3], with a recent focus on stem cells and regeneration.

Recent work suggests that the stability and robustness of cell populations depends on the structure of their interactions [4,5], more so than on the detailed molecular identity of the mediators of these interactions. This project will pursue an integrative understanding of which patterns of cellular interactions enable tissue-level behaviours, using tools of dynamical systems, statistical physics/stochastic processes, and inference methods. A particular focus will lie on extracting predictions as characteristic features of different model classes, to guide experimental measurements to distinguish between plausible mechanisms of cell population self-regulation. Successful students may be given the option to validate their theoretical work in collaboration with experimental labs.

Throughout the PhD, the student will acquire skills in mathematical methods and computational tools, gain an understanding of the broader research field, and learn to communicate with "wet lab" biologists. The student will have some freedom to define their own project in the context of the group’s research interests, and this is expected to increase as they progress through their PhD towards becoming an independent researcher.

Research environment

This is an opportunity to conduct your PhD research on mathematical and computational biology, embedded in a world-leading centre for multidisciplinary research in mammalian stem cell biology and regenerative medicine.

The student will benefit from active supervision with regular progress meetings, and from the active community at the Centre for Regenerative Medicine, with regular seminars by internal and invited speakers, as well as journal clubs. Training in professional and research skills will be tailored to the individual student’s background and training needs. The student will also have the opportunity to engage with the mathematical and systems biology research community at other departments in Edinburgh, to which the group maintains active connections.

Edinburgh is a vibrant city consistently ranked amongst the top places to live in the UK. You can find information about the University’s position on Brexit here: https://www.ed.ac.uk/news/eu

References

  1. Blanchard, Fletcher, Schumacher (2018). The devil in in the mesoscale: Mechanical and behavioural heterogeneity in collective cell movement. Seminars in Cell & Developmental Biology, (in press) https://doi.org/10.1016/j.semcdb.2018.06.003
  2. Schumacher, Maini, Baker (2017). Semblance of Heterogeneity in Collective Cell Migration. Cell Systems, 5(2), 119–127.e1. https://doi.org/10.1016/j.cels.2017.06.006
  3. Ding, Schumacher, Javer, Endres, Brown (2018). Common behavioural mechanisms underlie C. elegans aggregation and swarming. bioRxiv https://doi.org/10.1101/398370 
  4. Kunche, Yan, Calof, Lowengrub, Lander (2016). Feedback, Lineages and Self-Organizing Morphogenesis. PLoS Computational Biology, 12(3), 1–34. https://doi.org/10.1371/journal.pcbi.1004814 
  5. MacLean, Kirk, Stumpf (2015). Cellular population dynamics control the robustness of the stem cell niche. Biology Open, 4(11), 1420–1426. https://doi.org/10.1242/bio.013714 

Subject Areas

Bioinformatics, Biomedical Engineering, Biophysics, Cell Biology / Development, Computational Biology, Systems Biology, Mathematical Biology and Biological Physics

Other Information

Funding includes stipend, fees (UK/EU/overseas), and travel/research expenses.

Applicants should have a strong academic track record with a first or upper second class undergraduate degree (or equivalent), or a Master’s degree, in one of the following: mathematics, physics, computer science, engineering, or similar. A relevant postgraduate (Master’s or similar) degree is desirable. Graduates from a biological biomedical degree will be considered if they have strong skills and interest in quantitative approaches and relevant scientific programming experience.

Apply Now

Applicants should submit/arrange for submission the following documents to our e-mail address crm-training@ed.ac.uk by by December 10, 2018:

  1. Personal statement about your research interests and reasons for applying
  2. CV
  3. 2 x Reference letters 
  4. Marks for degrees awarded/ expected marks to be awarded

From Hematopoietic development towards generation of Hematopoietic stem cells

Deadline for applications - Thursday 13th December 2018

1st Supervisor: Prof Alexander Medvinsky
2nd Supervisor: Dr Val Wilson

Project Description

Haematopoietic stem cells (HSCs) give rise to the majority of cells in the adult haematopoietic system, however, their embryonic development is poorly understood. Embryonic stem (ES) cells can differentiate into all cells types of an adult animal. The recent successful generation of pluripotent ES-like (iPS) cells from cells of an adult organism has raised the hope of an effective treatment for tissue and organ deficiencies. As clonally-derived cell lines, pluripotent cells can be characterised, expanded, customised to meet needs of a patient, catalogued and stored in liquid nitrogen banks. Although ES and iPS cells can efficiently generate haematopoietic lineages in vitro they fail to generate transplantable long-term repopulating HSCs. The production of HSCs from pluripotent cells remains a considerable challenge for researchers around the world.

We have shown that mouse and human HSCs develop first in the AGM region and, more specifically, in the dorsal aorta. AGM-derived HSCs when transplanted into immunodeficient NSG mice can provide long-term high-level multilineage hematopoietic engraftment; the gold standard assay for functional HSCs. We have shown that these first HSCs have enormous regenerative potential and have put significant effort into the identification of secreted factors in the AGM region, which can drive development of the first HSCs.

The overall goal of this research proposal is to enhance haematopoietic differentiation from pluripotent cells with an ultimate goal of generating true human HSCs, based on our understanding of the early stages of embryonic HSC development.

Our studies have identified secreted factors in the mouse and more recently in the human AGM region. We hypothesise that some of these factors support HSC development from embryonic precursor cells by enhancing their self-renewal and differentiation potentials. Using human ES cell differentiation cultures, we will screen these factors for their capacity to elicit such an impact on ES-cell derived haematopoietic progenitors. 

The student will master both ES cell differentiation techniques and  experimental haematology methods . This will include in vitro assays, such as myeloid colony formation and T-cell differentiation as well as in vivo long-term transplantations. Other methods will include multi-colour flow cytometry (both analysis and sorting), confocal microscopy, qRT-PCR, RNAseq and genetic modification of ES cells. 

This project is a collaboration between two laboratories: Prof. Alexander Medvinsky (an expert in early haematopoietic development) and Prof. Val Wilson (an expert in early embryo development).   

References

  1. McGarvey, A. C., et al. (2017). "A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation." J Exp Med 214(12): 3731-3751. 
  2. Ivanovs, A., et al. (2017). "Human haematopoietic stem cell development: from the embryo to the dish." Development 144(13): 2323-2337. 
  3. Ivanovs, A., et al. (2011). "Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region." J Exp Med 208(12): 2417-2427.

Subject Areas

Biomedical Engineering, Cell Biology/Development

Funding Notes

Please complete the eligibility checklist which will provide a list of funding options and guide you through the application process. 

Apply now

  • Click here to complete our eligibility checklist*

You will then have the option to make a formal PhD application through the University’s online application system – EUCLID. You can apply for up to three projects on a single EUCLID application but you must complete a new checklist for each project if applying for more than one from the School of Biological Sciences.

*What is an Eligibility Checklist?
Our eligibility checklist is a short series of steps to check if you meet the criteria to apply for the PhD project you are interested in. 
It will also suggest funding schemes that you may be able to apply for based on your answers.
Your answers are not recorded and completing an eligibility checklist does not commit you to making a formal PhD application via EUCLID.

Tissue Repair PhD Programme

Up to seven Tissue Repair funded studentships will be available in September 2019 for outstanding students with a strong interest in Tissue Repair. Applications are now open (deadline 3rd December 2018).

The MRC Centre for Regenerative Medicine is one of five research centres at the Edinburgh Medical School involved in the four-year PhD Programme in Tissue Repair. This innovative, multi-disciplinary training programme seeks to train the next generation of scientific leaders in tissue repair by providing interdisciplinary training in basic and translational biomedical research. The programme is run by the University of Edinburgh and funded by the Wellcome Trust. For programme details please visit the Tissue Repair website.

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 can be found here.

Please contact the relevant PI’s informally to discuss potential projects and visit our funding opportunities page.

Centre Funded Studentships include:

  • Stipend for 3 or 4 years
  • Tuition Fees
  • Research Training Costs
  • Conference Travel Allowance

Further information about MRC Studentships.

Contact us for more information.