Fifty Shades of Fat: Using Computational Biology to Understand Liver Dysfunction

Synopsis

For an individual to remain healthy it is important that their body functions within certain physiological bounds. These bounds may range from complex processes such as the balance between cell death and cell division, to more simplistic measures such as body mass. Such balance is made more difficult because we live in an ever changing environment, exposing our bodies to a wide range of different chemicals every day. Dysregulation of these core body functions leads to conditions such as obesity, fatty liver and type 2 diabetes, which are estimated to cost the UK economy £2Bn per annum. Such dysregulation can be the result of many factors, including dietary overload, viral infection, or environmental stress. Understanding how the body adapts to these challenges and mitigates the risk of long-term adverse health impacts is key for the promotion of healthy aging in the UK population.

Within your body the liver acts as a gatekeeper, protecting you from toxic chemicals in the environment while ensuring the correct levels of many of the body's chemicals that are required for healthy life. To do this, the liver must be able to adapt to the environmental chemicals that it is exposed to, ensuring their safe handling, but at the same time keeping body chemicals within the physiological bounds required for healthy living. We have developed novel software that allows modelling of dynamic cell behaviors on a whole cell scale, meaning that the model will change and adapt to the chemical challenge. The goal of this predictive computer modelling approach is to identify molecules in the network that are critical to the liver's ability to balance the internal and external environment; such molecules are quite possibly disrupted in diseases such as metabolic syndrome, diabetes and cancer.

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