Address
UWS Campus, High St
Paisley PA1 2BE
Work Hours
Monday to Friday: 9AM - 5PM
About the Project
BACKGROUND. Intestinal stem cells (ISCs) are tightly regulated to balance differentiation with proliferation and maintain homeostasis. However, in the ageing intestine this balance is lost resulting in the dysplasia and declining tissue function that are associated with mortality. Drosophila ISCs are regulated by the same conserved signalling pathways that regulate mammalian epithelial stem cells making them an excellent model for homeostasis and ageing. While the major signalling pathways involved in regulation are known, the temporal dynamics of the signals and how they work together sequentially or synchronously to regulate fate are poorly understood. A major challenge in stem cell biology is that while signalling events may occur on a timescale of seconds the impact on cell fate may not be seen for many hours.
We have recently received a BBSRC Pioneer Award grant to support the development of new tools to study pathway dynamics. Based on published methods we have established live intravital confocal imaging of Drosophila intestinal stem cells in our lab. This allows us to combine live imaging of pathway activity at high temporal resolution with cell fate tracking over long time periods.
AIM. To understand the importance of signalling dynamics in stem cell regulation in vivo
OBJECTIVES
(1) Measuring signalling pathway dynamics in ISCs in vivo during homeostasis and ageing.
We will use live intravital confocal imaging of Drosophila ISCs to image fluorescent signalling pathway reporters
(2) Characterising the regulatory mechanisms that drive these dynamics
Cell-type specific RNAi and overexpression will be used to manipulate pathway components and assess interactions between pathways focussing on changes with age.
(3) Manipulate dynamics to change cell fate
Emerging deep learning-based image processing techniques will be used to develop models of signalling dynamics and their impact on cell fate. These models will be tested by changing the temporal profile of signalling and observing the effect on cell fate and tissue homeostasis.
Together these objectives will characterise the role of signalling dynamics in stem cell homeostasis and age-related mis-regulation in an important model system relevant to human intestinal health.
TRAINING
The project will involve multidisciplinary training across experimental biology and data analytics including image processing and machine learning. Training will be provided in a wide range of molecular biology techniques, genetics, confocal microscopy and image analysis.
HOW TO APPLY:
Applications should be made by emailing bbsrcdtp@liverpool.ac.uk 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 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 bbsrcdtp@liverpool.ac.uk. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to david.p.doupe@durham.ac.uk
The deadline for all applications is 12noon on Monday 22nd July 2024.
Part-Time Study Options
All NLD DTP PhDs are available as part time or full time, with part time being a minimum of 50% of full time. Please discuss potential part time arrangements with the primary supervisor before applying to the programme.
Project CASE Status
This project is not a CASE project. While individual applicant quality is our overriding criterion for selection, the NLD DTP has a commitment to fund 8 CASE projects per year – as such, CASE projects may be favoured in shortlisting applicants when candidates are otherwise deemed to be equal or a consensus on student quality cannot be reached.
Funding Notes
BBSRC NLD DTP programme – starting October 2024. UKRI provide the following funding for 4 years: • Stipend (2024/25 UKRI rate £19,237) • Tuition Fees at UK fee rate (2024/25 rate £4,786) • Research support and training grant (RTSG) Note – UKRI funding only covers UK (Home) fees.