Chameleon Spots

The overall goal of this project is to generate cell-based screening systems that can be used for the discovery of small molecules and biological products that have therapeutic potential in human disease. The pharmaceutical industry is striving to improve the effectiveness of its drug discovery programmes (i.e. improving drug discovery rates whilst decreasing clinical failure rates) by increasing the biological relevance of the assays through which it identifies and screens its drug candidates. This strategy has driven substantial growth in cell-based assay automation and in high-content screening over the past decade. In the last two years there has been increasing, data-driven, recognition that cells grown in standard culture conditions, as used in these assays, are physiologically different from, and display drug responses that are variable to similar cells within intact tissues, thus providing misleading and potentially inaccuate data. This disconnection cannot be addressed simply by the increased use of animal models due to low throughput, high costs and complexity limitations. Therefore, a strong drive now exists for 3D tissue-based model systems that reproduce the biochemical and physiological properties of intact tissues but ones can be used in high-throughput screening, thus resulting in improved drug discovery productivity and reducing the use of animals in research. The Stem Cell Biology Laboratory at King's College London will be primarily responsible for generating large human cell populations that can be configured into tissue-like cellular arrays for use in the project. Human embryonic stem (hES) cells, derived from the inner cell mass of 6-day old human blastocysts are pluripotent and thus capable of generating every cell type in the human body. Novel hES cell lines, generated in the Stem Cell Biology Lab under license from the Human Fertilisation and Embryology Authority, will be used to generate different types of cells that may have utility in drug discovery and toxicological screening programmes. The Stem Cell Biology Lab will generate a wide variety of brain-specific cell populations, as well as heart and liver cell types. The cells will be formed into tissue-like structures and grown for up to one month in unique culture conditions. The behaviour of the cells will be closely monitored over time and compared to analgous rodent tissues to determine how similar these cell populations are to real tissues. The overall goal of this project is to generate new human cell-based tissues for drug screening that can be used by the pharmaceutical industry to develop new drugs and biopharamaceutical products for human health.