Developing novel technologies to analyse cellular differentiation processes during embryonic development in vivo and ex vivo

Description

During embryogenesis, all cell types of the body are being established through carefully controlled differentiation processes. In mammals, one of these organ systems of central importance is the vasculature. Yet, there are still gaps in our understanding of how the cellular components of the vasculature are being specified and differentiated. Vascular smooth muscle cells (VSMCs), which form the cell layer enveloping the inner endothelial cells of blood vessels and control vascular tone and function, arise from a diverse range of sources. We have provided evidence that progenitor cells of VSMCs arise shortly after gastrulation and express the marker protein Wilms’ tumour 1, however, the molecular and cellular elements of the differentiation process are not clear.  

In this BBSRC-funded PhD project at the University of Liverpool, the appointed student will be trained in cutting edge technologies of embryonic stem cell-based culture methods and fluorescence and electron microscopy in order to establish a novel combined workflow of both imaging technologies. During visiting rotations at Newcastle University, the student will be trained in a complementary 3D electron microscopy approach in order to characterise cellular changes during VSMC differentiation processes. This will be combined with 2D and 3D fluorescence confocal and light sheet imaging approaches performed at University of Liverpool, allowing the student to address a range of aims including: 

1)    Determining the differentiation processes of VSMCs originating from Wt1-expressing progenitor cells using molecular marker analysis by fluorescence confocal and light sheet microscopy in mouse embryos and Gastruloids. 

2)    Defining ultrastructural changes during the differentiation process of VSMCs in mouse embryos and Gastruloids using Serial Block Face Scanning Electron Microscopy; 

3)    Combining both approaches of fluorescence and EM microscopy to establish a comprehensive understanding of the cellular changes involved in VSMC differentiation in the early mouse embryo.

Therefore, the project will provide the student with a highly sought-after skill set. By learning these techniques, the student will develop novel approaches that will enable a comprehensive analysis of structural characteristics combined with marker expression in order to provide a deeper understanding of the changes that take place during VSMC differentiation.

The student will be embedded in a vibrant research group focussed on various aspects surrounding the processes of embryonic development and VSMC differentiation and function. We are interested in candidates that wish to advance their skill sets in imaging techniques and data handling. The BBSRC is welcomes application from students from diverse backgrounds.

The student will engage with 2 important BBSRC Challenge areas:

1.   Lifelong Health: We will determine important developmental processes of differentiation of VSMCs, which will contribute to the understanding of fundamental mechanisms of ageing by analysing key developmental and cell biological processes.

2.   Biotechnology for Health: We will utilise new model systems (gastruloids) and establish novel technological and experimental approaches to improve mechanistic understanding of health. 

HOW TO APPLY

Applications should be made by emailing  with:

·        a CV (including contact details of at least two academic (or other relevant) referees);

·        a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, 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;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your IELTS or TOEFL English language certificate (where required);

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to . A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to 

The deadline for all applications is 12noon on Monday 9th January 2023. 

Availability

Open to students worldwide

Funding information

Funded studentship

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

Supervisors

References

The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature (2005) Development 132(23):5317-5328.
Mesothelium contributes to vascular smooth muscle and mesenchyme during lung development. (2008) PNAS 105(43):16626-30.
Restrictive differentiative capacity of Wt1-expressing peritoneal mesothelium in postnatal and adult mice (2021). Scientific Reports 11, 15940. doi: 10.1038/s41598-021-95380-1.
Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids (2018) Nature 562, 272–276.
A guide to analysis and reconstruction of serial block face scanning electron microscopy data (2018) J Microscopy 270: 217-234 doi: 10.1111/jmi.12676.