Elizabeth George, a Lab Head in the Models of Disease group, is determined to find new drug targets by modifying genes or how they are expressed. Before coming to Novartis, Elizabeth showed that the specific removal of a small segment of an extracellular matrix gene in mice reduces atherosclerosis, the disease that causes heart attacks. This experiment demonstrated how manipulating genes in animal models mimics human disease better than tissue culture assays. “Many human diseases are attributed to altered genotypes,” said Elizabeth, “Thus, analyzing genes that harbor those alterations can provide clues for drug discovery.”
The Models of Disease group provides a critical service for all disease area research groups at the Novartis Institutes of BioMedical Research (NIBR). Elizabeth describes the group as a team of experts that helps find novel drug targets by manipulating genes to create phenotypes that resemble human disease. “My specialty is phenotyping at the molecular level,” said Elizabeth, “My lab looks for and characterizes functional changes in animals that have been purposefully mutated.” Today’s geneticists can knock-out or overexpress specific genes in whole animals or in a particular organ or tissue, insert DNA into the genome, and even engineer whole chromosomes.
Mapping the human genome was a tremendous feat, but the key to drug discovery is finding which genes and gene products cause disease. You can either pick a suspect gene and delete, mutate, or overexpress it to see if the phenotype resembles a disease, or you can do mutagenesis screening where you create hundreds of random mutations and look for phenotypes that resemble disease. When you find such a phenotype, then you work backwards to determine which gene or genes caused it. “What motivates me,’ said Elizabeth, “is knowing that my research could contribute to the discovery and development of a useful therapeutic.”
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