Diabetes is a serious condition where the amount of sugar (glucose) in the blood is too high because the body either cannot produce enough of the hormone insulin or cannot use the insulin effectively. There is no known cure for diabetes, and although many treatment options are available, they often do not prevent the disabling long-term complications of the disease. In the search for new treatments, researchers are now trying to find drugs that will protect the insulin-producing (beta) cells of the pancreas. To support this research, the aim of this project is to develop a new 3D human cell-based model of pancreatic beta cell health. The model will be developed using freshly isolated human islets. The team will then investigate whether a more sustainable human cell source can be used and whether the model can be miniaturised, so more drugs can be tested in each assay. If the project is successful, it will enable the faster testing of potential new anti-diabetes drugs, and ultimately help to identify new and improved treatments for diabetes. If widely adopted, the resulting model will also reduce the number of animals currently used in diabetes research and drug discovery.

The pharmaceutical industry has relied on in vitro models of cancer using traditional cell lines and animal models for the progression of drug treatment of cancer with poor success. This failure could be attributed to poor models with currently available human cell lines (where cell lines have the ability to change their genetic makeup over time in culture away from the original tumour biology) and results obtained in animals not translating to man. The aim of this study is therefore to address this problem by development of an in vitro model using innovative 3D cell culture methodologies alongside novel genetically stable human lung tumour cell lines (which have been shown to maintain their key tumour characteristics after long-term culture). If successful, this model will allow for better understanding of the crosstalk between the numerous cell types involved in this complex disease and how new drugs can manipulate this process. In the longer term, this will hopefully lead to the development of more effective anti-cancer therapies, improved treatments for patients and ultimately a reduction in the use of animals in cancer research and drug discovery.

Many liver diseases result in the development of fibrosis, the excessive accumulation of extracellular matrix proteins. Over time this process can lead to cirrhosis (severe scarring), liver failure and often requires liver transplantation. Currently the development of drugs to treat liver fibrosis is heavily reliant on animal studies to model the complex processes involved. Although animal models of liver fibrosis have proved invaluable in understanding the development and progression of the disease, we are yet to see an anti-fibrotic drug on the market. This project aims to create a human 3D in vitro cell-based model of liver fibrosis. If successful, this model will allow the quicker evaluation of potential new anti-fibrotic drugs. In the longer term, this will hopefully lead to the development of more effective anti-fibrotic therapies, improved treatments for patients and ultimately a reduction in the use of animals in fibrosis research and drug discovery.