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The effect of pressure modulation on cell fate decisions during early development

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  • Full or part time
    Dr D Turner
    Dr B Geraghty
    Dr VR Kearns
    Prof Majlinda Lako
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

This exciting project offers an opportunity for a motivated student to contribute to new understanding of the influence of physical/mechanical signalling on cell decision making during development. Embryos undergo numerous, discrete cell-fate decisions that are often binary in nature. However, the processes by which individual cells actively adopt one fate at the expense of another is still an unresolved key question in biology. Most studies have focussed on disentangling the chemical and genetic inputs required for cell fate specification, without taking into account mechanical/physical signalling, and the pressures/forces that are present during early development.

We will take a multidisciplinary, embryonic stem cell (ESC) approach to dissect the relationship between physical and chemical signalling by developing an environmentally controlled system which will allow us to precisely modulate the pressure cells will be exposed. We will expose mouse ESCs to culture regimes that promote different cell fates, and determine whether there is a relationship between both the frequency or magnitude of pressure changes, and the dynamics of cell fate acquisition. This will allow us to extract general principles underlying fate choices during early embryo development, and the role of physical and chemical signalling has in underpinning these decisions.

The multidisciplinary supervisory team will provide training and support in all relevant laboratory, experimental and computational analysis techniques. The student will be based in the IACD at the University of Liverpool, which has strong bioengineering and developmental biology expertise. They will also spend time working in the Retinal Stem Cell Research Group at Newcastle University, where they will be trained organoid growth methods, as well as gaining exposure to a more biologically-focused research area.

All postgraduate research students (PGRs) undertake formal, personalised training at Liverpool, co-ordinated by the Liverpool Doctoral College. This creates a learning environment that allows PGRs to enhance their skills for a successful research experience and career. Participation in public and patient engagement events, for which the host department have won awards, is strongly encouraged.

This project is suited to a candidate with a Bachelor/Masters degree in an engineering discipline, and experience of finite element modelling. Knowledge of material characterisation of biological tissue and basics of the coding process, especially for MATLAB and/or LabView, are desirable but not essential. Upon completion, the candidate will have developed into a professional biomedical engineer capable of using engineering techniques to generate knowledge underpinning fundamental biological questions that could help solve complex clinical problems.

HOW TO APPLY
Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to [Email Address Removed]

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids; Nature (2018)

Anteroposterior polarity and elongation in the absence of extra-embryonic tissues, and spatially localised signalling in gastruloids: mammalian embryonic organoids; Development (2017)

Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells; Development (2014)

Brachyury cooperates with Wnt/β-catenin signalling to elicit primitive-streak-like behaviour in differentiating mouse embryonic stem cells; BMC Biology (2014)

Line-Field Optical Coherence Tomography as a tool for In vitro characterization of corneal biomechanics under physiological pressures; Scientific Reports (2019)

Microscale assessment of corneal viscoelastic properties under physiological pressures. Journal of the Mechanical Behaviour of Biomedical Materials (2019)

An integrated transcriptional analysis of the developing human retina. Development (2019)

Differentiation of Retinal Organoids from Human Pluripotent Stem Cells. Current Protocols in Stem Cell Biology (2019)



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