Kidneys filter circulating blood through a complex structure known as the glomerulus. This contains three interconnected biological barriers: a collagen‐rich basement membrane sandwiched between podocyte and endothelial cells (https://doi.org/10.1038/s41573‐021‐00242‐0). The importance of the glomerulus in kidney health and disease has led to widespread research into bioengineering methods that can replicate this cell structure in the laboratory (https://doi.org/10.1038/s41581‐021‐00528‐x). For example, it is well known that podocytes and endothelial cells can self‐assemble into simple cell structures that can subsequently lay down a basement membrane. Recently, Prof. Welsh (secondary supervisor on this project) showed that different biomaterials can be used to guide this self‐assembly process (doi.org/10.1002/adhm.201900698). We wish to build upon this work by incorporating a new 3D bioprinting approach known as in situ endothelialisation (doi.org/10.1002/adfm.201908349). This method, co‐developed by Dr Ouyang (co-supervisor) and Dr Armstrong (primary supervisor), allows us to 3D print biomaterials containing small channels that are lined with endothelial cells. This system can then be connected to syringe pumps and microfluidics to continuously perfuse these “blood vessels” with liquid media.
In this project, the PhD student will combine these methods to 3D print a perfusable cell model of the glomerulus. These cell organization within these printed glomeruli will be visualized as they are perfused and matured using confocal fluorescence microscopy and immunostaining. Finally, the barrier transport of fluorescent molecules and drugs will be studied in glomeruli printed with podocytes carrying disease mutations. This is a highly interdisciplinary project that draws on major advances in polymer chemistry, biomaterials science, kidney biology, and biological characterization. The student will benefit from the diversity of experience of the supervisory team and will be fully trained across all these techniques. The work will be largely conducted in the laboratories of the primary supervisor, who has broad expertise in biomaterials, 3D printing, microfluidics, and tissue engineering. These labs are based within the Dorothy Hodgkin Building (DHB), a state‐of‐the‐art research environment providing unrestricted access to onsite core facilities (e.g., cell culture, bioimaging, histology, molecular biology). The secondary supervisor (Prof. Gavin Welsh) is part of Bristol Renal, which is also based at the DHB, and will support the student in all aspects of kidney biology. The project is co‐supervised by experts in polymer synthesis and 3D printing (Dr Liliang Ouyang, Tsinghua University) and advanced bioimaging and image analysis (Dr Sero, University of Bath).
Our aim as the SWBio DTP is to support students from a range of backgrounds and circumstances. Where needed, we will work with you to take into consideration reasonable project adaptations (for example to support caring responsibilities, disabilities, other significant personal circumstances) as well as flexible working and part‐time study requests, to enable greater access to a PhD. All our supervisors support us with this aim, so please feel comfortable in discussing further with the listed PhD project supervisor to see what is feasible
University of Bristol, Bristol Medical School:
Bristol Medical School is the largest and one of the most diverse Schools in the University of Bristol, with approximately 1100 members of staff, 1350 undergraduate, 250 postgraduate taught and 240 postgraduate doctoral research students. The Head of School is Professor Ashley Blom. The Medical School has two departments: Population Health Sciences and Translational Health Sciences. The School is a leading centre for research and teaching across these areas. Research in the School is collaborative and multi-disciplinary, with staff coming from a wide range of academic disciplines and clinical specialties.
The 2021 Research Excellence Framework (REF) confirmed the University of Bristol’s position as a leading centre for health research. Bristol Medical School contributed to three Units of Assessment including UoA1 (Clinical Medicine), UoA2 (Public Health, Health Services and Primary Care) and UoA4 (Psychology, Psychiatry and Neuroscience). The UoA2 submission, comprising predominantly Medical School staff. was ranked 3rd in the UK with 94% of our submitted research outputs rated as world leading (4*) or internationally excellent (3*). Submissions to UoA1 and UoA4 were shared with varying degrees of representation with the Faculty of Life Sciences. Respectively UoA1 and UoA4 had 94% and 84% of submitted research ranked as 4* or 3*, which represented increases in each category in the proportions of 4* ranked papers as well in growth in GPA rankings above the previous REF2014.
How to apply:
Apply here. Search for South West Biosciences Doctoral Training Partnership (PhD) under 'find a programme' Full details on how to apply for this project can be found here
Funding includes a tax free stipend at UKRI rates (currently £17,668 for 22/23), research and training costs and tuition fees. Funding is also available for a limited number of international students.
Closing date:
Midnight, Monday 5th December 2022
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