The biophysics of pancreatic cancer, towards next generation in vitro models of disease.

Heriot-Watt University

About the Project

Current in vitro cell models and animals used in research are poor predictors of clinical outcomes because of interspecies differences to humans. It is estimated at over 90% of experiments conducted on animals lead to no human benefit and contributes heavily to the failure of new therapeutics in the drug development pipeline. In addition, current in vitro humanised disease modelling lacks the complexity of in vivo tissues, such as tissue’s 3D structure, mechanobiology and fluid pressure gradients leading to drug assessment results that cannot be repeated in the clinic. Yet, new drugs are desperately needed to combat a range of modern-day diseases, particularly solid cancers like pancreatic cancer (PDAC), the treatment for which has not improved in over 40 years. Organ-on-chip is an in vitro microfluidic based technology that promises to lead the way in reducing and replacing animal models in research and improve the way we model diseases in vitro. Organ-on-chip devices contain small culture chambers in which multiple cell types can be introduced, and small channels that feed culture medium and remove waste products, recapitulating interstitial tissue flow in a way not possible in static in vitro approaches (dishes/wells). This drives a more accurate tissue mimic, and for disease models, a more realistic cell model to test new drug approaches.

This project will involve the design and development of an organ-on-chip, microfluidic device to accurately model the biophysical and biochemical microenvironment of pancreatic cancer towards understanding disease progression, and developing new therapeutics to overcome these barriers. The student will:

1.      Investigate current state of the art in microfluidic disease modelling, particularly in cancer and develop an understanding of current limitations.

2.      Design and develop microfluidic, organ-on-chip devices towards recapitulating key disease hallmarks found in Pancreatic cancer in vivo, such as disease fibrosis and rigidity, hypoxia, interstitial pressures and methods for characterising these.

3.      In collaboration with cancer biologists and clinicians, use the PDAC-on-chip device to develop new approaches to improving drug delivery in pancreatic cancer and reducing disease aggression.

The student will be based at Institute of Biological Chemistry, Biophysics and Bioengineering (IB3). The student will have excellent opportunity to work with industry partners, and collaborators around the globe. The student will obtain in-depth knowledge and hands on training in microfluidic theory, design and fabrication, cell culturing techniques, both on and off chip, a range of biochemical and biophysical characterisation methods, such as cell viability assays, immunofluorescence and live cell staining, confocal microscopy, atomic force microscopy and rheology and more.  The student will help contribute to the development of next generation disease models of cancer for improving drug discovery and reducing the use of animal models in research.

Funding:

This exciting 3.5-year PhD studentship is funded by Heriot-Watt University. Stipend and fees will be based on UKRI levels. Note these levels increase on an annual basis due to inflation, with 2024/2025 stipend due to be £19,237. Tuition fees covered for international students.

Candidate Requirement:

The successful candidate must have (or expect to obtain) a 1st or strong 2:1 degree in biomedical engineering, biophysics, biochemistry, biosciences, and/or any other relevant disciplines at university level. 

How to Apply:

Apply Online

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