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PhD opportunities

Available PhD positions are advertised below. Please use the links/guidance on each project for how to apply (deadlines 5th and 8th January 2020).

EASTBIO: Modelling cell state transitions in differentiating embryonic stem cells

1st Supervisor: Prof Valerie Wilson
2nd Supervisor: Dr Linus Schumacher
3rd Supervisor: Dr Jochen Kursawe (University of St Andrews)

EASTBIO: Dissecting the role of the immune system in tumour initiation using experimental & computational analysis
1st Supervisor: Dr Yi Feng
2nd Supervisor: Dr Linus Schumacher
EASTBIO: Role of HYPPO/YAP signalling in early development of the haematopoietic system 1st Supervisor: Prof A Medvinsky
2nd Supervisor: Dr Paul Reynolds (University of St Andrews)
Biochemical analysis of the interaction of pluripotency transcription factors with RNA polymerase enzymes 1st Supervisor: Prof I Chambers
Forward engineering of pattern formation: Models and experiments towards predictive multicellular self-organisation 1st Supervisor: Dr G Blin
EASTBIO: Forward engineering of pattern formation: Models and experiments towards predictive multicellular self-organisation 1st Supervisor: Dr G Blin
2nd Supervisor: Dr Linus Schumacher
EASTBIO: Discovering regulatory principles for the thymic epithelial progenitor/stem cell state 1st Supervisor: Prof C Blackburn
2nd Supervisor: Dr R Grima
Precision Medicine: A novel data integration method for cellular social networks within self-organising multicellular systems 1st Supervisor: Dr Guillaume Blin
2nd Supervisor: Dr Linus Schumacher
3rd Supervisor: Dr Thanasis Tsanas
Precision Medicine: The role of transcription factors and the signaling environment in commitment of cells into the germline 1st Supervisor: Prof Ian Chambers
2nd Supervisor: Dr Tamir Chandra
Precision Medicine: Illuminating roles of Wnt/b-Catenin signalling in nonalcoholic fatty liver disease (NAFLD) 1st Supervisor: Prof Keisuke Kaji
2nd Supervisor: Dr Simon Tomlinson
1st Supervisor: Prof Jonathan Fallowfield
Precision Medicine: Analysis of signaling pathways underlying development of human haematopoietic stem cells (HSCs) 1st Supervisor: Prof Alexander Medvinsky
2nd Supervisor: Prof Keisuke Kaji
3rd Supervisor: Dr Al Ivens
Precision Medicine iCASE: Modelling Sex Dependent Differences in Human Liver Disease using Stem Cell Derived Models and Organ on a Chip Devices 1st Supervisor: Dr David Hay
2nd Supervisor: Prof Philippa Saunders

EASTBIO: Modelling cell state transitions in differentiating embryonic stem cells

Applications accepted up to 5th January 2020 (UK/EU) 

1st Supervisor: Prof Valerie Wilson
2nd Supervisor: Dr Linus Schumacher
3rd Supervisor: Dr Jochen Kursawe (University of St Andrews)

About the project

Cellular behaviour in development, regeneration and cancer is often classified by defining various cell states, which may for example describe the propensity of cells to divide or differentiate, or to assume different modes of motility. In many cases, we know little about how cells integrate complex queues to regulate their states. To address this, in silico mathematical modelling can  be used to formulate hypotheses on cell state control, which can then be tested by comparing with experimental data on varying culture conditions in vitro. An abundance of data exists in the field, comprising snapshots of cell populations at single-cell resolution, yet there are few quantitative predictive models of cell states and their regulatory networks. Integrating such models with data will enable us to optimise experiments to produce the most informative data and accelerate the testing of differentiation protocols in cell culture. 

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 statistical modelling of cell state transitions. Models will be calibrated against population and single-cell data to quantify the cell state transition rates, and how these change under different culturing conditions. We have developed a preliminary modelling approach (extending on [2]) and statistical analysis pipeline to 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 computational tools for modelling and analysis of cell state transitions. The student will experimentally test predictions from the model. Depending on the student’s interests, the project can then be taken into several further directions, such as working with human cell lines, scaling the method to work with transcriptomics data, or quantifying spatial variation of gene expression in stem cell colonies using RNAscope.

This project is a great opportunity for students with previous experience in mathematics or statistics and interest 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.

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 & St. Andrews.

References

  1. Tsakiridis, A., Huang, Y., Blin, G., Skylaki, S., Wymeersch, F., Osorno, R., … Wilson, V. (2014). Distinct Wnt-driven primitive streak-like populations reflect in vivo lineage precursors. Development, 141(6), 1209–1221. https://doi.org/10.1242/dev.101014
  2. Gupta, P. B., Fillmore, C. M., Jiang, G., Shapira, S. D., Tao, K., Kuperwasser, C., & Lander, E. S. (2011). Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells. Cell, 146(4), 633–644. https://doi.org/10.1016/j.cell.2011.07.026

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body.

Apply Now

For instructions on how to apply for an EASTBIO PhD studentship please refer to http://www.eastscotbiodtp.ac.uk/how-apply-0

All applicants must download the EASTBIO application form (from http://www.eastscotbiodtp.ac.uk/how-apply-0) and submit the completed document and their academic transcript to crm-training@ed.ac.uk

Please ensure that referees send their completed reference forms  (also available from http://www.eastscotbiodtp.ac.uk/how-apply-0) to crm-training@ed.ac.uk.

EASTBIO: Dissecting the role of the immune system in tumour initiation using experimental & computational analysis

Applications accepted up to 5th January 2020 (UK/EU) 

1st Supervisor: Dr Yi Feng
2nd Supervisor: Dr Linus Schumacher

About the project

The mechanisms that modulate the pre-neoplastic stage of tumourigenesis in vivo are largely unknown due to the lack of suitable animal models. Our previous work with a zebrafish tumour initiation model has revealed a supportive role of the host innate immune system during pre-neoplastic development. Our in vivo live imaging studies allowed us to directly visualize leukocyte (neutrophils and macrophages) migration toward the pre-neoplastic cell (PNC) at its inception, however the precise identity of attractants that modulate leukocyte migration toward the PNC remain unclear. So far, we have identified H2O2 as one of the earliest signals required for leukocyte recruitment to the PNC, analogous to that of leukocyte recruitment following tissue damage. More recently, we found that leukocytes take advantage of pre-existing gaps in the basement membrane to gain access to PNCs, and PNCs residing in the vicinity of the basement membrane gap gain growth advantage due to increased interaction with leukocytes. Our data suggest that in vivo both mechanical and chemical factors impact on leukocyte recruitment and interaction with PNCs. Previously, an inference-based computational approach was used to extract information concerning the spatio -temporal properties of the putative attractants from in vivo inflammatory cell migration during wound inflammation [3]. Here we propose to develop a similar computational framework based on existing approaches to analyse leukocyte dynamics in the PNC niche. We aim to determine spatio-temporal properties of the attractants within the PNC niche, and to characterise the dynamics of leukocyte retention therein so as to generate a testable hypotheses concerning the underlying molecular mechanism. Based on the analysis of our findings, we will attempt to modulate the PNC niche so as to test the hypotheses. More importantly, we will examine PNC progression under conditions where leukocyte recruitment toward the PNC is altered. Ultimately, a better understanding of how leukocytes sense the environment, integrate incoming signals and navigate in vivo in the PNC niche will provide us with an opportunity to target leukocyte/ PNC interaction, and subsequently block PNC development for therapeutic intervention.

The student will receive training in relevant ‘wet lab’ techniques and microscopy/image analysis, while working with existing preliminary data and computational tools for modelling and analysis of immune cell migration.

This project is a great opportunity for students with previous experience in mathematics or statistics and interest in computer programming. The student will benefit from integration in an active biomedical research environment at the Centre for Inflammation Research and Centre for Regenerative Medicine.

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. The student will also have the opportunity to engage with the mathematical and systems biology research community at other departments in Edinburgh.

References

  1. Ramezani T., et al. Live Imaging of Innate Immune and Pre-neoplastic Cell Interactions using an Inducible Gal4/UAS Expression System in Larval Zebrafish Skin. JoVE (2015) Feb. PMCID: PMC4354608
  2. van den Berg et al. Proteolytic and Opportunistic Breaching of the Basement Membrane Zone by Immune Cells during Tumor Initiation. Cell Rep. (2019) 27(10):2837-2846. PMID: 31167131
  3. Weavers, et al. Systems Analysis of the Dynamic Inflammatory Response to Tissue Damage Reveals Spatiotemporal Properties of the Wound Attractant Gradient. Curr. Biol. 2016;26(15):1975–1989. http://dx.doi.org/10.1016/j.cub.2016.06.012.

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body.

Apply Now

For instructions on how to apply for an EASTBIO PhD studentship please refer to http://www.eastscotbiodtp.ac.uk/how-apply-0
Contact Dr Yi Feng Yi.Feng@ed.ac.uk and Dr Linus Schumacher Linus.Schumacher@ed.ac.uk before you apply.
Please submit all required documents directly to CIR.Postgraduate@ed.ac.uk
We anticipate that our first set of interviews will be in the week commencing 10th February 2020 with awards made the following week.

EASTBIO: Role of HYPPO/YAP signalling in early development of the haematopoietic system

Applications accepted up to 5th January 2020 (UK/EU/Overseas) 

1st Supervisor: Prof A Medvinsky
2nd Supervisor: Dr Paul Reynolds (University of St Andrews)

About the project

During embryonic development blood cells emerge from the endothelium of embryonic vasculature through the process called endothelial-to-haematopoietic transition (EHT). However, molecular mechanisms that underpin EHT remain poorly understood. Our preliminary data indicate that Hippo/YAP signalling is involved in blood specification during embryo development and in differentiation of embryonic stem (ES) cells. Hippo/YAP signalling is involved in various biological processes including regulation of organ sizes and tumorigenesis. This signalling is also involved in making cell fate choices, which can be triggered purely by mechanical forces, through the process called mechanotransduction. We hypothesise that mechanotransduction leads to Hippo/YAP-mediated switching of specific genes that are responsible for differentiation of blood cells from the embryonic endothelium.

In this interdisciplinary Project we will investigate the role of Hippo signalling and mechanotransduction in mammalian haematopoietic development using human ES cells as a model.

Our specific aims are:

  1. Generation of fluorescent reporter cell lines to visualise haematopoietic differentiation and involvement of Hippo signalling in this process.
  2. Analysis of Hippo/YAP signalling components in haematopoietic specification using overexpression and knockdown strategies in ES cells.
  3. Analysis of the role of mechanotransduction in haematopoietic development using modulation of physical properties of substrates.

Methods. i. ES cell culture and differentiation; ii. confocal microscopy; iii. flow cytometry; iv. molecular biology (including CRISPR/Cas9, shRNA, ES cells transgenesis, QRT-PCR); v. single-cell transcriptome analysis; vi. interrogation of cell differentiation using physical forces; vii. Bioinformatics. Student will use a bioinformatics approach and collaborate with mathematicians and physicists – specialists in computer modelling to create a theoretical model for the role of mechanotransduction in haematopoietic development. The student will acquire expertise in haematopoietic development, gene manipulations, mechanotransduction and bioinformatics.

This is a collaborative project between 4 laboratories in the University of Edinburgh, University of Glasgow and the University of St. Andrews. Their expertise lie in haematopoietic development and differentiation (Prof. A. Medvinsky); cell signalling (Dr. P. Reynolds); role of physical forces in cell behaviour and differentiation (Dr. M. Vassalli); Bioinformatics (Dr. Al Ivens).

References

  1. Medvinsky, A., et al. (2011). "Embryonic origin of the adult hematopoietic system: advances and questions." Development 138(6): 1017-1031.
  2. Dupont, S., et al. (2011). "Role of YAP/TAZ in mechanotransduction." Nature 474(7350): 179-183.
  3. Dege, C. and C. M. Sturgeon (2017). "Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells." J Vis Exp(129).

Apply Now

Apply Online link will take you to our Online Application checklist. Complete each step and download the checklist which will provide a list of funding options and guide you through the application process. Follow the instructions on the EASTBIO website (you will be directed here from our application checklist), ensuring you upload an EASTBIO application form and transcripts to your application, and ticking the box to request references. Your referees should upload their references using the EASTBIO reference form, in time for the 5th January deadline so please give them plenty of time to do this by applying early.

Biochemical analysis of the interaction of pluripotency transcription factors with RNA polymerase enzymes

Applications accepted up to 5th January 2020 (UK/EU/Overseas) 

1st Supervisor: Prof I Chambers

About the project

Pluripotent stem cells possess the dual defining properties of self-renewal and multi-lineage differentiation potential. To retain an effective differentiation capacity, self-renewal must occur at high efficiency. Self-renewal is controlled by the action of sequence specific DNA binding transcription factors (TFs), with the TF NANOG showing a direct correlation between concentration and self-renewal efficiency (Chambers et al. 2003, 2007). However, the mechanisms by which pluripotency TFs communicate to the biochemical machinery that makes RNA is surprisingly poorly understood. In new work, our lab has shown that NANOG directly contacts the large subunit of RNA Polymerase II (RNAP2), through the RNAP2 C-terminal domain (CTD). This interaction can by dissociated by CDK9, the enzyme that causes release of RNAP2 from pause sites downstream of the transcription start site. This project will take multiple in-cell and in vitro approaches to examine the interactions of RNAP2 and NANOG with specific chromatin sites. In addition, the effects of expression of additional NANOG interacting proteins on the interaction of NANOG with RNAP2 will be assessed. This project will deliver a fuller understanding of how NANOG interacts with partner proteins to drive transcriptional change.

The student will receive training to become proficient in biochemical analysis of transcription factor function, analytical molecular biology, confocal microscopy, genome editing and cell culture. The student will be provided with development opportunities to enable them to fully exploit their results as well as having access to transferable skills training.

http://www.crm.ed.ac.uk/research/group/embryonic-stem-cell-biology

References

  1. Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S. and Smith, A. G. (2003). Functional expression cloning of Nanog, a pluripotency sustaining factor in mouseembryonic stem cells. Cell 113, 643-655
  2. Chambers, I., Silva, J., Colby, D., Nichols, J., Robertson, M., Nijmeijer, B., Vrana, J., Jones, K., Grotewold, L. and Smith, A. (2007) Nanog safeguards pluripotency and mediates germ cell development. Nature, 450, 1230-1234

Apply Now

Apply Online link on this page will take you to our Online Application checklist. Please complete each step and download the checklist which will provide a list of funding options and guide you through the application process.
If you would like us to consider you for one of our scholarships you must apply by 5 January 2020 at the latest.

Forward engineering of pattern formation: Models and experiments towards predictive multicellular self-organisation

Applications accepted up to 5th January 2020 (UK/EU/Overseas) 

1st Supervisor: Dr G Blin

About the project

Background:
The aim of developmental biology is a complete understanding of how the embryo develops, how embryonic cells acquire their fate and how they arrange in time and space to create complex organisms.

Reverse engineering is the predominant approach in the field. Yet, a modern and complementary approach consists in applying forward engineering principles to biology:
instead of performing perturbation experiments in embryos or cell culture to pick apart the underlying mechanisms of development, forward engineering employs a bottom-up approach to devise biological systems with predictable properties. The implicit goal of this strategy is to gain quantitative insights into biological processes while at the same time exploring alternative designs not selected by evolution (Davies 2018, Tewary et al. 2018).

Project:
This PhD project aligns with the forward engineering mind-set.

We have recently shown that embryonic stem cells can form patterns spontaneously when the cells are confined in space in vitro (Blin et al, 2018). Recent preliminary work has focused on mathematical models offering plausible explanations for this process.
We can now take this research further:
The aim of this PhD project is to build novel theoretical models capable of describing the emergence of asymmetric patterns of cell fates from an initially homogenous population of cells
Key questions to address include:

  • What is the minimal number of rules sufficient to elicit spontaneous symmetry breaking in a stem cell population?
  • What are the key design principles that are necessary to confer robustness and plasticity to a patterning process?
  • How do cues from the microenvironment (geometry, scale, chemistry) influence the patterning process designed during this project?

Importantly, the models created during this project will be experimentally tested using a combination of cell biology, quantitative imaging, micro-fabrication techniques and synthetic biology approaches available in the host lab

Impact:
This project will help us gain quantitative insights into the interplay between the various fundamental rules which are required to build a robust self-organised system. We will better understand the sensitivity of a developing multicellular system to the environment and its initial conditions. This will help us generate precise engineering guidelines for the production of bio-manufactured systems for medical applications (organ on chip or implantable mini-organs). We will also test current questions in systems and evolutionary biology.

Training and Environment

    The candidate will have the opportunity to be trained in the wet lab to test his/her own models experimentally, thus developing so-called T-Shaped skills (combining depth in one specialisation with the skill to collaborate across disciplines).

    This will be enabled by a multidisciplinary team of supervisors dedicated to offer an environment that nurtures the candidate’s aspiration to become a skilled researcher at the interface of several disciplines. The project is sufficiently open to enable the candidate to become a creative thinker and develop his/her own ideas.

    The candidate will be based in the MRC-CRM in the Little France campus in Edinburgh and will be associated with the lab of quantitative biology of pattern formation (http://www.crm.ed.ac.uk/research/group/quantitative-biology-pattern-formation).

    Our lab is a new multidisciplinary group focusing on the mechanisms of patterning during development and tissue regeneration. We work closely with the Schumacher group who develops mathematical models to formulate principles that apply to multiple biological systems in order to gain insight into misregulation in disease, and inform improvements to regenerative therapy (http://www.crm.ed.ac.uk/research/group/computational-biology-cell-populations).

    The candidate will also benefit from close interaction with:

    • The DARTH group located within walking distance from SCRM, focusing on state of the art signal processing and statistical machine learning techniques across diverse healthcare applications: https://www.darth-group.com/
    • The Cachat lab part of the SynthSys institute (http://www.synthsys.ed.ac.uk/) which possesses cutting edge synthetic biology knowledge and technologies.

    We are looking for an excellent candidate with a strong academic background in science and engineering with a genuine interest in developmental biology, tissue regeneration and more broadly to the way nature builds itself.

    This project could suit an applicant with training in biology who is interested in learning mathematical or computational approaches, or an applicant with training in mathematics or computer science who is keen to develop an interest in biology.

    References

    1. Geometrical confinement controls the asymmetric patterning of brachyury in cultures of pluripotent cells. Blin G, Wisniewski D, Picart C, Thery M, Puceat M, Lowell S. Development. 2018 Sep 21;145(18). pii: dev166025. doi: 10.1242/dev.166025.
    2. Using synthetic biology to explore principles of development. Davies J. Development. 2017 Apr 1;144(7):1146-1158. doi: 10.1242/dev.144196. Review. PMID: 28351865
    3. Stem cell bioengineering: building from stem cell biology. Tewary M, Shakiba N, Zandstra PW. Nat Rev Genet. 2018 Oct;19(10):595-614. doi: 10.1038/s41576-018-0040-z. Review. PMID: 30089805

    Apply Now

    Apply Online link on this page will take you to our Online Application checklist. Please complete each step and download the checklist which will provide a list of funding options and guide you through the application process.
    If you would like us to consider you for one of our scholarships you must apply by 5 January 2020 at the latest.

    EASTBIO: Forward engineering of pattern formation: Models and experiments towards predictive multicellular self-organisation

    Applications accepted up to 5th January 2020 (UK/EU/Overseas) 

    1st Supervisor: Dr G Blin
    2nd Supervisor: Dr Linus Schumacher

    About the project

    Background:
    The aim of developmental biology is a complete understanding of how the embryo develops, how embryonic cells acquire their fate and how they arrange in time and space to create complex organisms.

    Reverse engineering is the predominant approach in the field. Yet, a modern and complementary approach consists in applying forward engineering principles to biology:
    instead of performing perturbation experiments in embryos or cell culture to pick apart the underlying mechanisms of development, forward engineering employs a bottom-up approach to devise biological systems with predictable properties. The implicit goal of this strategy is to gain quantitative insights into biological processes while at the same time exploring alternative designs not selected by evolution (Davies 2018, Tewary et al. 2018).

    Project:
    This PhD project aligns with the forward engineering mind-set.

    We have recently shown that embryonic stem cells can form patterns spontaneously when the cells are confined in space in vitro (Blin et al, 2018). Recent preliminary work has focused on mathematical models offering plausible explanations for this process.
    We can now take this research further:
    The aim of this PhD project is to build novel theoretical models capable of describing the emergence of asymmetric patterns of cell fates from an initially homogenous population of cells
    Key questions to address include:

    • What is the minimal number of rules sufficient to elicit spontaneous symmetry breaking in a stem cell population?
    • What are the key design principles that are necessary to confer robustness and plasticity to a patterning process?
    • How do cues from the microenvironment (geometry, scale, chemistry) influence the patterning process designed during this project?

    Importantly, the models created during this project will be experimentally tested using a combination of cell biology, quantitative imaging, micro-fabrication techniques and synthetic biology approaches available in the host lab

    Impact:
    This project will help us gain quantitative insights into the interplay between the various fundamental rules which are required to build a robust self-organised system. We will better understand the sensitivity of a developing multicellular system to the environment and its initial conditions. This will help us generate precise engineering guidelines for the production of bio-manufactured systems for medical applications (organ on chip or implantable mini-organs). We will also test current questions in systems and evolutionary biology.

    Training Outcomes 

      The candidate will have the opportunity to be trained in the wet lab to test his/her own models experimentally, thus developing so-called T-Shaped skills (combining depth in one specialisation with the skill to collaborate across disciplines).

        This will be enabled by a multidisciplinary team of supervisors dedicated to offer an environment that nurtures the candidate’s aspiration to become a skilled researcher who can work at the interface of several disciplines. The project is also sufficiently open to enable the candidate to become a creative thinker and develop and communicate his/her own ideas.

        References

        1. Geometrical confinement controls the asymmetric patterning of brachyury in cultures of pluripotent cells. Blin G, Wisniewski D, Picart C, Thery M, Puceat M, Lowell S. Development. 2018 Sep 21;145(18). pii: dev166025. doi: 10.1242/dev.166025.
        2. Using synthetic biology to explore principles of development. Davies J. Development. 2017 Apr 1;144(7):1146-1158. doi: 10.1242/dev.144196. Review. PMID: 28351865
        3. Stem cell bioengineering: building from stem cell biology. Tewary M, Shakiba N, Zandstra PW. Nat Rev Genet. 2018 Oct;19(10):595-614. doi: 10.1038/s41576-018-0040-z. Review. PMID: 30089805

        Apply Now

        Apply Online link will take you to our Online Application checklist. Complete each step and download the checklist which will provide a list of funding options and guide you through the application process. Follow the instructions on the EASTBIO website (you will be directed here from our application checklist), ensuring you upload an EASTBIO application form and transcripts to your application, and ticking the box to request references. Your referees should upload their references using the EASTBIO reference form, in time for the 5th January deadline so please give them plenty of time to do this by applying early.

        EASTBIO: Discovering regulatory principles for the thymic epithelial progenitor/stem cell state

        Applications accepted up to 5th January 2020 (UK/EU/Overseas) 

        1st Supervisor: Prof C Blackburn
        2nd Supervisor: Dr R Grima

        About the project

        T cells are vital regulators and effectors of the adaptive immune system. Production of a functional, self-tolerant T cell repertoire is a complex process that occurs in a dedicated organ, the thymus, and depends on a set of highly specialized epithelial cells that form a key part of the thymic stroma (thymic epithelial cells; TEC)(1). Two main sub-lineage of TEC exist: cortical and medullary TEC. These arise from a common progenitor/stem cell during thymus development, and are functionally distinct, regulating early T cell differentiation and central tolerance induction respectively.

        In previous work, we identified the thymic epithelial progenitor/stem cells (TEPC) from which the TEC lineage first arises (2) and showed these cells can form self-organised thymic organoids in vitro (unpublished) and upon transplantation (2). Recently, we have also established that TEC can be generated in vitro by direct reprogramming of primary embryonic fibroblasts using a single transcription factor, FOXN1 (3). Like ex vivo TEPC, these ‘induced TEC’ (iTEC) can generate a thymus upon transplantation and form thymic organoids in vitro (3). Additionally, we have recently uncovered part of the mechanism controlling the very earliest development of the medullary TEC sublineage, which regulates central tolerance induction (4). We now wish to use the iTEC system to test predictive models of intrinsic and extrinsic regulation of TEPC regulation.

        This interdisciplinary project is based at the interface of stem cell biology and state-of-the-art informatics analysis of transcriptome and epigenomic data. It will use a combination of bioinformatics, modelling and wet-lab approaches to predict and test regulatory networks that control the TEPC state and initiate TEC differentiation.

        The successful student will receive training in stem cell biology, bioinformatics analysis of single cell and population RNAseq and ATACseq data, modelling of transcriptional networks, CAS9/CRISPR mediated genetic modification, tissue culture including of pluripotent stem cells, microdissection, cellular reaggregation techniques, thymic organoid culture, multiparameter FACS analysis, advanced imaging analysis, immunohistochemistry, RT-qPCR.

        References

            1. Manley, NR, Richie, ER, Blackburn, CC, Condie, B, Sage, J. (2011) Structure and function of the thymic microenvironment. Front Biosci. 17 2461-77.
            2. Bennett, A.R., Farley, A., Blair, N.F., Gordon, J., Sharp. L., and Blackburn, C.C.; (2002) Identification and characterization of thymic epithelial progenitor cells. Immunity 16 803-814
            3. Bredenkamp, N., Ulyanchenko, S., O’Neill, K.E., Manley, N.R., Vaidya, H.J. and Blackburn, C.C. (2014) An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts. Nature Cell Biology, 16 902-8.
            4. Liu, D., Kousa, A.I., O’Neill, K.E., Guillemot, F., Popis, M., Farley, A.M., Tomlinson, S.R., Ulyanchenko, S., Seymour, P.A., Serup, P., Koch, U., Radtke, F., and Blackburn, C.C. (2019) Canonical NOTCH signaling controls the early progenitor state and emergence of the medullary epithelial lineage in fetal thymus development. BIORXIV/2019/600833

            Apply Now

            Apply Online link will take you to our Online Application checklist. Complete each step and download the checklist which will provide a list of funding options and guide you through the application process. Follow the instructions on the EASTBIO website (you will be directed here from our application checklist), ensuring you upload an EASTBIO application form and transcripts to your application, and ticking the box to request references. Your referees should upload their references using the EASTBIO reference form, in time for the 5th January deadline so please give them plenty of time to do this by applying early.

              

            Precision Medicine: A novel data integration method for cellular social networks within self-organising multicellular systems

            Applications accepted up to 8th January 2020 (UK/EU)

            1st Supervisor: Dr Guillaume Blin
            2nd Supervisor: Dr Linus Schumacher
            3rd Supervisor: Dr Thanasis Tsanas

            About the project

            The quantification and interrogation of how the cells organise and interact with their environment is fundamental for advancing developmental biology, cancer research, pharmaceutics and medical diagnostics.

            Our lab has recently published quantitative image analysis tools capable of measuring the collective organisation and the history of cellular interactions within crowded cellular environments such as 3D stem cell cultures, tumours or whole mammalian embryos (Blin et al., 2019). The technology generates rich multi-dimensional datasets that expert scientists can use for hypothesis-driven data exploration and analysis.

            However, a robust method that can extract meaningful information from such datasets in an unbiased and automated fashion is missing. One of the reasons is that image analysis frameworks able to process complex multicellular systems are only emerging, thus the need for a novel data integration method is only now being realised.

            The other reason is the unfamiliar structure of the data: In such datasets, data points are feature vectors that summarise individual cell state at each time point. What differs from conventional time series is that data points also form nodes within multiple graph layers: cellular lineage trees are reconstructed and data points are connected to form binary trees with typed relationships (identity/mother/daughter/sister) forming branches that can be grouped into diverse categories. In addition, direct cell neighbours are identified for each individual cell to form a ‘cellular social network’ that changes over time.

            We decide to call such a dataset CeLINet for Cell Lineages Interaction Network.

            Importantly both experimental and synthetic CeLINets are readily available in our lab (Blin et al., 2019; Wang et al., 2018). Others have also published annotated datasets and made these publicly available (McDole et al., 2018). With the advances in imaging techniques such datasets will multiply rapidly and we anticipate that a data integration framework that will enable biologist and medical scientists to detect and visualise hidden patterns within CeLINets will quickly grow.

            We are convinced that CeLINets will become transformative in our ability to 1) comprehend developing multicellular systems 2) detect subtle phenotypes in comparative analyses and 3) increase the robustness of our quantitative image analysis tools. Yet, while research for statistical inference on (non-connected) lineage trees is just emerging (Hicks et al., 2019), a theoretical framework for complete CeLINets analysis remains to be established.

            Aims

            The aims of this PhD project are to build on recent theoretical work in order to:

            1. Define a formal mathematical description of CeLINets;
            2. Build a new data integration method for data pattern recognition and enhanced data visualisation;
            3. Test the ability of the new method to classify phenotypes and make predictions using in vitro models of development available in the lab as well as other datasets that are readily publicly available;
            4. Test the new method for data imputation in order to restore ‘broken’ lineage trees due to missing frames in real world datasets and improve current cell tracking methods in dealing with such a situation.

            One of the deliverables of this PhD will be a widely applicable open source computational framework for the analysis and exploration of CeLINets. Individual modules of this framework will be unit tested with synthetic data generated from agent based models with known features readily available in the lab. 

            Training Outcomes 

            • Developing so called T-shaped skills combining depth in data science specialisation with the skill to collaborate and communicate across disciplines (developmental biology, medical science, computational biology and image analysis)
            • Graph theory and statistics: Developing unique expertise in lineage tree statistics and large scale social network analysis, thus establishing a unique yet adaptable scientific identity
            • Machine learning: Understanding the principles of supervised learning and statistical mapping, developing functional relationships to associate variables with clinical outcome. This also includes data visualization, and formal statistical model assessment.
            • Programming skills: Understand and apply modular software architecture, test driven development, code versioning and requirements of sustainable software practices
            • Developmental biology: Acquire a conceptual understanding of key processes in developmental biology in order to interpret real-world datasets
            • Imaging and Image analysis: Acquire knowledge in imaging and image analysis techniques in order to understand real-world datasets
            • Scientific communication: Communicate complex ideas orally and in writing to both a specialist and lay audience across disciplines

            References

                1. 1. Blin, G., Sadurska, D., Migueles, R.P., Chen, N., Watson, J.A., and Lowell, S. (2019). Nessys: A new set of tools for the automated detection of nuclei within intact tissues and dense 3D cultures. PLOS Biology 17, e3000388.
                2. 2. Hicks, D.G., Speed, T.P., Yassin, M., and Russell, S.M. (2019). Maps of variability in cell lineage trees. PLOS Computational Biology 15, e1006745.
                3. 3. McDole, K., Guignard, L., Amat, F., Berger, A., Malandain, G., Royer, L.A., Turaga, S.C., Branson, K., and Keller, P.J. (2018). In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level. Cell 175, 859-876.e33.
                4. 4. Wang M., Tsanas A., Blin G., Robertson D. : Investigating motility and pattern formation in pluripotent stem cells through agent-based modeling, 19th IEEE International Conference on BioInformatics and BioEngineering, Athens, Greece, 28-30 October 2019 (in press)

                Apply Now

                Click here to Apply Now. The deadline for 20/21 applications is Wednesday 8th January 2020.
                Please note all applications for the Precision Medicine DTP should be submitted to University of Edinburgh, even those applying for a project at the University of Glasgow.
                Applicants must apply to a specific project, ensure you include details of the project you are applying to in Section 4 of your application. We encourage you to contact the primary supervisor prior to making your application.  
                As you are applying to a specific project, you are not required to submit a Research Proposal as part of your application. 
                Please ensure you upload as many of the requested documents as possible at the time of submitting your application.  

                Precision Medicine: The role of transcription factors and the signaling environment in commitment of cells into the germline

                Applications accepted up to 8th January 2020 (UK/EU)

                1st Supervisor: Prof Ian Chambers
                2nd Supervisor: Dr Tamir Chandra

                About the project

                In mammals, specification of the germline occurs shortly after implantation. Understanding how germ cells become specified is important both to inform the treatment of human infertility, for example through in-vitro spermatogenesis, and for the wider field of regenerative medicine. The proposed work is a follow-on project from our studies showing that the transcription factor OTX2, restricts entry of pluripotent cells into the germline (Zhang et al. 2018). In cultures of wild type cells, expression of primordial germ cell (PGC) transcription factors (TFs) does not increase for over 24 hours after changing the culture to PGC differentiation media containing BMP4. This increase in PGC TF expression is preceded by a decrease in the level of Otx2, suggesting that BMP4 may suppress Otx2 expression, thereby stimulating entry to the germline. Consistent with this, Otx2 null cells enter the germline at enhanced efficiencies of >80% and Otx2 null cells can enter the germline even in the absence of BMP4. However, the efficiency of the latter process is only 30% indicating that cytokines provide additional functions in addition to Otx2 repression. Our published studies also show that, in the absence of Otx2, the PGC TF, Blimp1 is not required for the initial stages of germline entry but is required for cells to develop a mature PGC transcriptome. This project will use single cell transcriptomic analyses to investigate the changes occurring at early time points during germline differentiation of wild-type cells, Otx2-/- cells and cells carrying compound mutations in Otx2-/- and selected PGC TF genes. These studies will reveal the important genomic changes required to enable subsequent efficient germline differentiation.

                Aims

                1. to determine whether Otx2+/+ and Otx2-/- cells express the same genes when they initiate PGC-like differentiation
                2. to determine at what stage PGC-like differentiation goes awry in Otx2-/-;Blimp1-/- cells. Analyses will be extended to Otx2-/- cells deleted for the additional PGC TFs Prdm14 and AP2g.
                3. to determine the chromatin structural changes occuring during progression of differentiation from ESC è EpiLC è PGC-like cells using single cell ATAC-seq

                Training Outcomes 

                The student will be trained in a combination of wet and dry lab techniques. CRISPR/Cas9-mediated gene disruption in embryonic stem cells will be used to generate new lines for study (Otx2-/-;Prdm14-/- and Otx2-/-;AP2g-/-). Cell culture approaches to differentiating ESCs to germline competent EpiLCs and further differentiation into initial PGC-like cells will be provided. In addition, single cell biochemical techniques will be employed to generate high throughput libraries. Training will also be provided in statistical techniques required to analyse and interpret single cell sequencing data.

                References

                    1. Zhang, J., Zhang, M., Acampora, D., Vojtek, M., Yuan, D., Simeone, A. and Chambers, I. Otx2 restricts entry to the mouse germline. Nature, 562, 595–599.
                    2. Zhang, M. and Chambers, I. Segregation of the mouse germline and soma. Cell Cycle, accepted.

                    Apply Now

                    Click here to Apply Now. The deadline for 20/21 applications is Wednesday 8th January 2020.
                    Please note all applications for the Precision Medicine DTP should be submitted to University of Edinburgh, even those applying for a project at the University of Glasgow.
                    Applicants must apply to a specific project, ensure you include details of the project you are applying to in Section 4 of your application. We encourage you to contact the primary supervisor prior to making your application.  
                    As you are applying to a specific project, you are not required to submit a Research Proposal as part of your application. 
                    Please ensure you upload as many of the requested documents as possible at the time of submitting your application.  

                    Precision Medicine: Illuminating roles of Wnt/b-Catenin signalling in nonalcoholic fatty liver disease (NAFLD)

                    Applications accepted up to 8th January 2020 (UK/EU)

                    1st Supervisor: Prof Keisuke Kaji
                    2nd Supervisor: Dr Simon Tomlinson
                    1st Supervisor: Prof Jonathan Fallowfield

                    About the project

                    Non-Alcoholic Fatty Liver Disease (NAFLD) caused by a high fat diet (HFD) is a growing major public health problem world-wide. About 30% of people are in the early stage of NAFLD in UK, and about 10-30% of people who have NAFLD develop Non-Alcohol Related Steatohepatitis (NASH), a more serious condition of NAFLD, which can lead to cirrhosis, the third most common cause of death in people aged 45-65 years. A pathological feature of adult NAFLD typically starts with triglyceride accumulation in hepatocytes near the central veins. However, it is unclear why triglycerides are preferentially deposited in this area of the liver.  Understanding the underlying molecular mechanism may lead to the development of strategies to treat, diagnose and ultimately develop a preventative medicine.

                    The pericentral area near the central veins in the liver is where Wnt/b-catenin signaling is active. Notably, hepatocyte specific b-catenin knockout mice were shown to have very small triglyceride accumulation in the liver whereas transgenic mice developed a severe NAFLD phenotype under a HFD condition (Behari, Am. J. Pathol, 2014). However, several known direct b-catenin target genes in the liver under a normal diet condition cannot explain the role of b-catenin in NAFLD. Since b-catenin targets change depending on expression of other TFs and/or activity of other signaling pathways even within the same cells, we hypothesized that b-catenin changes its targets in response to the HFD condition and activates genes involved in NAFLD.

                    Aims

                    In this project, we aim to detect genome-wide b-catenin binding sites and identify direct target genes critical for NAFLD development. Currently, the most common strategy to identify direct transcription factor (TF) binding sites is ChIP-seq. However, b-catenin ChIP-seq has been difficult to successfully perform. Thus, we apply an alternative technique called DNA adenine methyltransferase identification with sequencing (DamID-seq) which we have recently optimized in mouse cells (Tosti, Genome Research, 2017). DamID-seq is based on the expression of a TF tethered to the DNA adenine methyltransferase (Dam) from E.Coli and does not require immunoprecipitation or crosslinking, thus it is suited for proteins which bind to DNA indirectly and/or for which ChIP-seq is difficult (Vogel, Nature Protocol, 2007).

                    We will first establish an in vivo b-catenin DamID-seq system generating mouse lines with inducible b-catenin-Dam expression in a wide range of cell types. Using this system, we will identify direct b-catenin binding sites in pericentral and periportal hepatocytes isolated from mice fed a normal or high fat diet. We will also perform RNA-seq with the same hepatocyte subpopulations. Together with RNA-seq datasets from the 1000 liver tissue samples in the SteatoSITE project lead by Prof Fallowfield  (https://steatosite.com/)we will identify b-catenin binding sites and candidate genes critical for NAFLD development and progression. Finally we will validate the importance of these gene and their regulatory regions in an in vitro 3D organoid NAFLD model (Kozyra, Scientific Reports, 2018), using the CRISPR/Cas9-mediated genome modification.

                    Training Outcomes 

                    This project involves a wide range of cellular and molecular biology techniques including DamID-seq, 3D organoid culture, CRISPR/Cas9-mediated genome modification, as well as mouse handling, histological analyses, flow cytometry, and imaging. Under the supervision of the basic scientist, Prof Kaji, and the clinical scientist, Prof Fallowfield, the PhD student will learn all these techniques as well as biology of the liver. Dr Tomlinson, a Senior Lecturer in Bioinformatics, and the bioinformatics course at MRC CRM will offer training for the next generation sequencing data processing. We therefore expect the student will be fully equipped with biological and computational knowledge as well as interpersonal work skills to start their career as a researcher after their PhD.

                    Apply Now

                    Click here to Apply Now. The deadline for 20/21 applications is Wednesday 8th January 2020.
                    Please note all applications for the Precision Medicine DTP should be submitted to University of Edinburgh, even those applying for a project at the University of Glasgow.
                    Applicants must apply to a specific project, ensure you include details of the project you are applying to in Section 4 of your application. We encourage you to contact the primary supervisor prior to making your application.  
                    As you are applying to a specific project, you are not required to submit a Research Proposal as part of your application. 
                    Please ensure you upload as many of the requested documents as possible at the time of submitting your application.  

                    Precision Medicine: Analysis of signaling pathways underlying development of human haematopoietic stem cells (HSCs)

                    Applications accepted up to 8th January 2020 (UK/EU)

                    1st Supervisor: Prof Alexander Medvinsky
                    2nd Supervisor: Prof Keisuke Kaji
                    3rd Supervisor: Dr Al Ivens

                    About the project

                    Haematopoietic stem cells (HSCs) are broadly used in the clinic to treat blood disorders, but there is a shortage of these cells to meet clinical demands. Despite extensive efforts, the search for methods to produce high quality HSCs in the laboratory has had only limited success, mainly due to poor understanding of how these cells first emerge in the embryo. This project will address this gap by investigating molecular mechanisms leading to the generation of adult-type HSCs in the human embryo. 

                    During development, HSCs emerge in the embryonic aorta-gonads-mesonephros (AGM) region and possess enormous regenerative potential, significantly exceeding that of HSCs from adult tissues. Determining the mechanisms underpinning this high regenerative potential could pave the way to generating bona fide HSCs in the laboratory from alternative cell sources such as pluripotent (ES/iPS) cells. While ES/iPS cells can produce blood cells, they fail to generate bona fide HSCs in culture. This raises important questions: which intrinsic genetic factors missing in ES cells are responsible for HSC formation in the human embryo and how do extrinsic niche (microenvironment) factors regulate HSC development? We will identify such genes and functionally characterize their action using combinatorial gene interrogation (reprogramming strategies) empowered by bioinformatics analysis. Using state-of-the-art single cell transcriptome analyses we will (1) identify which genes are working in HSCs of the human AGM region, but not in their less regenerative counterparts that are derived from human pluripotent (ES) cells and (2) introduce these genes into human pluripotent (ES) cells, to determine their effects on production of blood cells and thereby identify genes that may enhance production of transplantable HSCs.  Resultant datasets will be used to (3) generate a computational model that integrates genetic regulators of HSCs and their microenvironment, which will be a highly valuable resource in the field.

                    Training Outcomes 

                    The student will learn: i. tissue culture methods and haematopoietic differentiation of human ES cells; ii. multi-colour flow cytometry and confocal microscopy; iii. reprogramming methodology using complex lentiviral libraries for combinatorial Dox-inducible overexpression of genes; iv. quantitative skills: analysis of single-cell transcriptomics datasets and computational modelling of cell-cell molecular interactions.

                    References

                        1. Ivanovs, A., et al. (2017). "Human haematopoietic stem cell development: from the embryo to the dish." Development 144(13): 2323-2337
                        2. Ruetz, T., et al. (2017). "Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming." Cell Stem Cell 21(6): 791-805 e799
                        3. Wang, S., et al. (2019). "Cell lineage and communication network inference via optimization for single-cell transcriptomics." Nucleic Acids Res 47(11): e66.

                        Apply Now

                        Click here to Apply Now. The deadline for 20/21 applications is Wednesday 8th January 2020.
                        Please note all applications for the Precision Medicine DTP should be submitted to University of Edinburgh, even those applying for a project at the University of Glasgow.
                        Applicants must apply to a specific project, ensure you include details of the project you are applying to in Section 4 of your application. We encourage you to contact the primary supervisor prior to making your application.  
                        As you are applying to a specific project, you are not required to submit a Research Proposal as part of your application. 
                        Please ensure you upload as many of the requested documents as possible at the time of submitting your application.  

                        Precision Medicine iCASE: Modelling Sex Dependent Differences in Human Liver Disease using Stem Cell Derived Models and Organ on a Chip Devices

                        Applications accepted up to 8th January 2020 (UK/EU)

                        1st Supervisor: Dr David Hay
                        2nd Supervisor: Prof Philippa Saunders

                        About the project

                        Metabolic syndrome is a cluster of conditions, which include increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels. This increases the individual’s risk of developing liver and heart disease, stroke and diabetes. Our interest lies in human liver disease and more specifically, liver steatosis. Liver steatosis is associated with imbalance between lipid formation and breakdown, glucose production and catabolism, and cholesterol synthesis and secretion, which are risk factors for developing non-alcoholic fatty liver disease (NAFLD).  While the liver can be steatotic, without disturbing normal function, NAFLD does progress to non-alcoholic steatohepatitis (NASH) in many patients. In NASH steatosis is combined with inflammation and results tissue fibrosis, with up to 20% of patients with NASH going onto develop cirrhosis of the liver.

                        NAFLD susceptibility varies across the population, however, both obesity and insulin resistance play a strong role in the disease process. Epidemiological studies show sex and age differences are important factors in developing fatty liver disease and metabolic syndrome, suggesting that sex hormones play important roles. Sex steroid hormone deficiency in post-menopausal women and in ageing men, predispose the older population to the metabolic syndrome and NAFLD (1-2). Notably, NAFLD is twice as common in post-menopausal women as in pre-menopausal women that could be consistent with a protective role of oestrogens in NAFLD although this remains under-explored (3).

                        Androgens and oestrogens regulate lipid, glucose and cholesterol homeostasis differently in men and women. For example, testosterone in men favours liver glucose metabolism, whereas in females it impairs it. Additionally, androgens reduce lipid accumulation in male livers, but increase lipid storage in females. In the context of cholesterol metabolism, both oestrogen and androgens decrease serum cholesterol and circulating LDL levels, promoting bile formation in females and liver accumulation in men. Oestrogens have an impact on inflammatory processes. In summary, sex hormones are important drivers for the fundamental differences observed in human metabolism and disease outcomes. There is an urgent need to better understand these differences at the molecular level as a platform for developing new and novel ways to therapeutically intervene in the context of human NAFLD.

                        Aims

                        To define the molecular basis for sex dependent differences in the development of non-alcoholic fatty liver disease as the basis for developing novel therapies to correct the aberrant phenotype.

                        Methods

                        We will use our novel NAFLD model which employs pluripotent stem cell derived hepatocyte like cells (HLCs) (4). During hepatocyte specification, male and female HLCs will be exposed to physiologic relevant levels of androgen, oestrogen and growth hormone signaling. Following hormone treatment, stem cell derived HLCs will be exposed to ‘normal’ and fatty diets. The interaction of hormone signaling and the development of steatosis will be studied ‘in the dish’ using our semi-automated platform, with a focus on key changes in liver cell biology, including hepatic metabolism and function, cell viability, gene transcription and factor secretion. Following in-depth analysis using bioinformatics coupled with target identification, the sex specific models developed from these studies will be further sophisticated using organ on a chip systems. The gene regulatory datasets derived in static and perfused culture will be used as a basis to restore hepatocyte homeostasis by reversing steatosis and/or reducing inflammatory gene expression. Studies will benefit from a close collaboration with an industrial partner and an opportunity to work in different laboratories to gain experience in a broad range of methods and different working environments.

                        References

                            1.  M. C. Carr, “The emergence of the metabolic syndrome with menopause,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 6, pp. 2404–2411, 2003. 
                            2.  M. Zitzmann, “Testosterone deficiency, insulin resistance and the metabolic syndrome,” Nature Reviews Endocrinology, vol. 5, no. 12, pp. 673–681, 2009. 
                            3.  L. Carulli, et al, “Gender, fatty liver and GGT,” Hepatology, vol. 44, no. 1, pp. 278–279, 2006. 
                            4.  M. Lyall et al, “Modelling non-alcoholic fatty liver disease in human hepatocyte-like cells,” Phil Trans B, 373(1750). pii: 20170362.

                            Training Outcomes 

                            PhD students will be provided access to state of the art facilities and technologies during their PhD project. The project is one that spans the research interests of the Hay and Saunders’ groups but is a new collaboration – the student will benefit from expert training in a wide range of methods and the chance to interact with groups in both the Centre’s for Regenerative Medicine and Inflammation ensuring an interdisciplinary training.

                            Student will also be provided with training opportunities provided by the Institute for Academic Development. During the course of the PhD, the student will be expected to attend and present at the MRC CRM seminar series and to present the outcomes of their studies at local and international meetings. This is key to student development, identifying new networking opportunities, building capacity within the field and delivering impact. Additionally, the student will have the opportunity to work within industry to develop liver on a chip systems and a three month placement at Novo Nordisk Research Centre Oxford to translate the technology. Novo Nordisk is a global healthcare company with more than 90 years of innovation and leadership in diabetes care - PhD students will be provided access to state of the art facilities and technologies during their PhD project. The project is one that spans the research interests of the Hay and Saunders’ groups but is a new collaboration – the student will benefit from expert training in a wide range of methods and the chance to interact with groups in both the Centre’s for Regenerative Medicine and Inflammation ensuring an interdisciplinary training.

                            Student will also be provided with training opportunities provided by the Institute for Academic Development. During the course of the PhD, the student will be expected to attend and present at the MRC CRM seminar series and to present the outcomes of their studies at local and international meetings. This is key to student development, identifying new networking opportunities, building capacity within the field and delivering impact. Additionally, the student will have the opportunity to work within industry to develop liver on a chip systems and a three month placement at Novo Nordisk Research Centre Oxford to translate the technology. Novo Nordisk is a global healthcare company with more than 90 years of innovation and leadership in diabetes care - http://www.novonordisk.co.uk/

                            Apply Now

                            Click here to Apply Now. The deadline for 20/21 applications is Wednesday 8th January 2020.
                            Please note all applications for the Precision Medicine DTP should be submitted to University of Edinburgh, even those applying for a project at the University of Glasgow.
                            Applicants must apply to a specific project, ensure you include details of the project you are applying to in Section 4 of your application. We encourage you to contact the primary supervisor prior to making your application.  
                            As you are applying to a specific project, you are not required to submit a Research Proposal as part of your application. 
                            Please ensure you upload as many of the requested documents as possible at the time of submitting your 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. 

                            The programme is based at the MRC 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

                            Tissue Repair PhD Programme

                            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 multi-disciplinary training programme is training the next generation of scientific leaders in tissue repair by providing interdisciplinary training in basic and translational biomedical research. 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.