Cells are located in a continuously evolving and dynamic microenvironment, where cells are stimulated by both cell-cell interactions, the extracellular matrix, chemicals and mechanical stimuli. This niche dictates cellular function. Cellular responses and interactions to their surroundings are fundamental and integral part of most cellular processes, including during development and regenerative processes.
Consequently, a tightly regulated plastic and adaptable cellular response is necessary for healthy development, organ homeostasis and in regenerative processes. However both the matrix and the cellular ability to integrate these interactions changes during ageing, and subsequently lead to cellular and organ defects, such as increased fibrosis and an impaired ability to regenerate, such as in wound healing processes. So far the precise underlying changes have been challenging to study in detail, and the current understanding of this process is therefore poorly understood. Our ability to dictate the composition of the matrix, combined with the capacity to both measure and change the mechanical properties within the matrix and study the cellular dynamics in 3D allows us to probe this central interplay, which will drive fundamental insights into why ageing occurs.
We will therefore integrate new advanced techniques including label free quantitative phase imaging (Digital holography and phase-resolved optical coherence microscopy) and Optical coherence tomography (OCT) combined with a powerful semiautomatic bioengineering platform, to characterise, manipulate and model the in vivo environment. Our unique setup allows us to probe fundamental cellular processes dynamically at the single cell resolution, while still replicating in vivo scenarios.
A cellular signalling pathway termed the Hippo pathway has prominent functions in regulating stemness, development, fibrosis and the ability of organs to regenerate. The Hippo pathway is a machanotransductive pathway that is central to cells and organs ability to feel and respond to force. The project will take advantage of a suite of generated genome edited Hippo cell models, and combine our powerfull experimental setup with iterative rounds of further genome editing of candidate genes.
This will allow the PhD candidate to functionally analyse in detail fundamental cellular processes that drives ageing. Exciting experimental results will be examined further using the high content Operetta imaging platform and we will explore particular exciting findings in depth using a collection of well-established molecular biology based techniques and “omics” based approaches.
Overall, our approach takes advantage and combine recently developed and complimentary techniques that overcome the fundamental limitations of static 2D mammalian cell model systems. The project seeks to analyse the central interplay between the cellular matrix, physical forces and its impact on the cellular functions in ageing.
This interdisciplinary project suits a motivated candidate that want to be trained in a supportive environment, and work at the interface of biomedical engineering, physics and cellular signalling. We are looking for a motivated team player, who is scientifically curious, driven and most importantly excited about making fundamental discoveries.
For instructions on how to apply for an EASTBIO PhD studentship please refer to http://www.eastscotbiodtp.ac.uk/how-apply-0
Contact Dr Carsten Hansen [Email Address Removed] before you apply.
We anticipate all EASTBIO (online) interviews will be in the week 8-12 February 2021 with awards made the following week.
Please submit all required documents directly to [Email Address Removed]
The research group is located in the University of Edinburgh Centre for Inflammation Research; a world-class research environment at the interface between biological and medical science, with multidisciplinary groupings focused on inflammation, infection, disease and repair. The Centre is based within the Edinburgh Medical School in the outstanding facilities of the Queen’s Medical Research Institute at the site of the Royal Infirmary of Edinburgh hospital, maximising future translational opportunities.
This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is open to UK and international students and provides funding to cover stipend and UK level tuition fees. The UoE covers the difference between home and international fees. There is a cap on the number of international students the DTP can recruit so it is important to know in which fees status category applicants fall under when formally applying.
Refer to UKRI website https://www.ukri.org/our-work/developing-people-and-skills/find-studentships-and-doctoral-training/get-a-studentship-to-fund-your-doctorate/ and Annex B of the UKRI Training Grant Terms and Conditions https://www.ukri.org/wp-content/uploads/2020/10/UKRI-291020-guidance-to-training-grant-terms-and-conditions.pdf for full eligibility criteria.
1: Rausch, V. and Hansen, C.G. The Hippo Pathway, YAP/TAZ, and the Plasma Membrane. Trends in cell biology 30, 32-48 (2020).
2: Rausch, V…. Hansen, C.G. The Hippo Pathway Regulates Caveolae Expression and Mediates Flow Response via Caveolae. Current biology : CB 29, 242-255 e246 (2019).
3: Gillies, D. ... Bagnaninchi, P.O. Real-time and non-invasive measurements of cell mechanical behaviour with optical coherence phase microscopy. Methods, 2018 Mar 1;136:126-133. doi: 10.1016/j.ymeth.2017.10.010. Epub 2017 Oct 31.