Gene regulation in health and disease

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A simple organism like C.Elgans has similar numbers of genes as a human even though it is made of only a few thousand cells compared to the many trillions in a human. This massive increase in complexity is therefore not linked to the genes themselves, but rather to the complexity of the combinations in which they are used. Therefore, complex mammalian life is founded on exquisite control of gene usage (expression); when and where they are switched on and off and their level of expression. The “switches” that control gene expression are located in the “non-coding” region of the genome rather than the regions that form the blueprint for production of the proteins of which we are made. However, this represents ~98% of the total genome and the DNA code that activates these switches is different in each cell type so understanding the systems that control gene expression is extremely complex. However, understanding these mechanisms is extremely important for human heath as nearly 90% of the genetics linked to all common human diseases (Heart disease, cancer, dementia, multiple sclerosis etc) lie within this region and change the activity of these switches. We use a combination of experimental, computational and machine learning approaches to understand the basic principles of gene regulation to decode common human disease genetics. We use these approaches to understand the genes and cellular functions affected by these genetics to ultimately guide therapeutic development.