A high throughput human vascularised 3D in-vitro model of adipose tissue to replace animal testing in drug development for metabolic dysfunction

Obesity is a rising epidemic and a risk for many comorbid conditions such as type 2 diabetes, coronary artery disease, and some cancers. Our developed understanding so far has identified macrophage-mediated chronic inflammation in the adipose tissue as a key element in disease mechanisms. However, the development of novel therapies targeting macrophages has been hampered by the lack of suitable in-vitro models.

In this PhD project, we will develop the first high-throughput human vascularized 3D bioprinted in-vitro model of adipose tissue that captures the role of macrophages, and that effectively simulates metabolic dysfunction as an alternative to animal models.

We will build on the extensive experience of our lab in developing novel biomaterial bioinks, to develop a unique biomimetic hydrogel composition that enables the 3D co-culture of macrophages with adipocytes. These will be bioprinted using established methods in our lab to develop a vascualrised adipose tissue model. Different sources of cells will be investigated including isolated primary human tissue cells and induced pluripotent stem cells (iPSCs). The bioprinted system will be designed to be able to mimic adipose tissue changes in metabolic dysfunction. This model would provide an alternative to animal testing to develop a better understanding of the pathophysiology of metabolic dysfunction and to identify and test novel therapies. 

The PhD position will be based in Biomedical Sciences in the Faculty of Life Sciences (http://www.bristol.ac.uk/life-sciences/) with access to leading edge infrastructure from the Bristol Bioprinting Centre (https://www.perrimangroup.co.uk/bioprinting), Blood and Transplant Research Unit (http://www.bristol.ac.uk/btru/ e.g. proteomics, flow cytometry, tissue culture) and the Wolfson Bioimaging Facility (http://www.bristol.ac.uk/wolfson-bioimaging/).

The PhD student will be part of three research groups with extensive expertise in in-vitro modelling, cell culture, biomaterials, bioprinting, imaging and advanced image analysis techniques. Dr Boussahel’s lab is part of the Perriman group in multi-laboratory space across the Biomedical Sciences Building, which includes the Bristol Bioprinting Centre. The Armstrong group is based in state-of-the-art lab space in the Dorothy Hodgkin Building, with access to cell culture facilities and specialised iPSCs culture units, with established iPSCs culture and differentiation protocols. The Ash Toye group with comprehensive multi-laboratory state of art labs, and facilities including flow cytometry, human samples processing and cell isolation facilities. In addition to this the PhD student will have access to state-of-the-art research facilities within the University of Bristol including the Wolfson Bioimaging Facility, histology, flow cytometry and proteomics facilities.

The PhD student will obtain full technical training from the three research groups in all the skills required for this project including primary cell isolation, culture and differentiation, 3D bioprinting, tissue engineering and cell characterisation including advanced imaging and image analysis, staining and histology, flow cytometry, gene expression analysis, etc. The PhD student will also have access to a comprehensive training programme offered by the Bristol Doctoral Training College at the University of Bristol.

If you are interested in this position please contact [Email Address Removed] and submit an application here.  

Supervision and training:

• Primary supervisor Dr Asme Boussahel
• Secondary supervisor Dr James Armstrong
• Third supervisor Professor Ash Toye