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PhD opportunities

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

*EPSRC* Analysis of mechanical forces in embryonic development of the haematopoietic system

Deadline for applications - Friday 27th July 2018

1st Supervisor: Prof Alexander Medvinsky
2nd Supervisor: Dr Pierre Bagnaninchi

Background

Haematopoietic stem cells (HSCs) lie at the foundation of the adult haematopoietic hierarchy and, through a fine balance between self-renewal and differentiation, maintain haematopoiesis throughout an animal’s lifespan. Elucidating mechanisms underlying HSC development is of fundamental significance with clinically relevant implications. The regulatory interactions between stem cells and their niches is a key issue in stem cell biology and physical forces are an important factor known to be involved in stem cell regulation. We have shown previously that HSCs emerge in the ventral domain of the embryonic dorsal aorta within the area called the aorta-gonad-mesonephros (AGM) region. The AGM region is subjected to compression and stretching forces during morphogenesis. Notably, physical stiffness is an important factor playing a role in HSC physiology in adult bone marrow. Using enforced reaggregation of AGM cells, we have been able to recapitulate HSC development in vitro, which supports our hypothesis that physical forces play a role in this process. We have also revealed a complex spatially polarised signalling milieu in the AGM region which is important for HSC development. We hypothesise that uneven physical tensions play a role in patterning expression of genes which underlie HSC development in the AGM niche.

Aims

The main objective of this project is to establish whether physical forces generated during embryogenesis play a role in patterning polarized gene expression in the AGM niche. Specific aims are: Aim 1) to spatially and temporally map AGM stiffness using bespoke high resolution optical coherence elastography tomography (OCT) microscope. Briefly, the low coherent light from a superluminescent diode is collimated into a custom scanning head and optics into an inverted microscope. The back propagating spectral interferences will then be resolved on a spectrometer to retrieve in-depth microstructural information. In the elastography mode, images will be acquired at the same location to record change in displacement (phase) to subsequently compute a strain map indicative for tissue stiffness. OCT method can uniquely map tissue elasticity with high resolution (5 μm) at 2mm depth. This will allow us to image and map mechanical properties of the AGM region for the first time in intact embryos, avoiding potential artefacts associated with dissection. Stiffness conditions will be then modelled in culture and effects studied at gene expression levels. Aim2) to determine impact of cell compression on gene expression. Tissue compression will be studied using a piezoelectric loading system which will then be used to replicate similar mechanical conditioning in vitro, e.g. by compression of cell-seeded gels. We will study effects of compression and stretching on various cell populations from the AGM niche to monitor modulation of expression of transcription factors and secreted molecules involved in HSC development. Bioinformatics analysis will be employed to process the data.

Training Outcomes

During PhD study, the student will be trained in analysis of physical properties of biological tissues and cell deformation complemented by methods of biological analysis such as flow cytometry cell sorting, cell culture, RT-PCR, RNA-Seq and confocal microscopy.

Other Information

This project is eligible for EPSRC funding and is open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date).

References

  1. Medvinsky, A., Rybtsov, S., and Taoudi, S. (2011). Embryonic origin of the adult hematopoietic system: advances and questions. Development 138, 1017-1031.
  2. Gillies, D. et al, (2017). Real-time and non-invasive measurements of cell mechanical behaviour with optical coherence phase microscopy, Methods, ISSN 1046-2023, https://doi.org/10.1016/j.ymeth.2017.10.010.
  3. Ivanovska I. et al., (2015). Stem cell mechanobiology: diverse lessons from bone marrow. Trends in Cell Biology, v25, No9, 523 -532.

Subject Areas

Bioinformatics, Cell Biology/Development, Immunology, Medical/Biomedical Physics, Medical Imaging

Apply Now

Please follow the instructions on how to apply https://www.ed.ac.uk/biology/prospective-students/pgr/how-to-apply

Tissue Repair PhD Programme

Applications are now closed for this programme 

Funded studentships available for Wellcome Trust PhD Programme inTissue Repair.

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

We encourage enquiries 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.