1 December 2015

Yvonne Rozendaal about being a PhD student in the RESOLVE consortium

Yvonne Rozendaal is a PhD student for the RESOLVE consortium in the Computational Biology group at Eindhoven University of Technology, the Netherlands. Her research focusses on building computational models to unravel the underlying pathways of the Metabolic Syndrome.

The Metabolic Syndrome is a cluster of co-morbidities, including obesity, elevated blood pressure, insulin resistance (diabetes type 2), and dyslipidemia (high triglyceride levels, low HDL-cholesterol levels). From these symptoms it is evident that both the systems that are responsible for glucose and lipid regulation are affected. This makes it hard to unravel what is the underlying cause that result in the onset and progression of this disease, and what possible treatment options would be targeted at.

As you can image, we cannot simply open up a patient to see which and how organs and tissues are affected. Nevertheless, we can easily perform measurements to assess the glucose and lipid levels in the blood at many different time points during the disease development. However, the concentrations in the blood are only balances of exchange fluxes between for example the liver and adipose tissue. From only these concentrations we cannot unravel what and how different organs and tissues play a role in the onset and progression of the Metabolic Syndrome.

However, from the literature we know the different functions that different organs and tissues exhibit. Using this biological information, together with the measured data, we can project the measured information onto this scheme of the regulatory system, and translate this into equations that describe the exchange and conversion of various metabolites between e.g. the liver, adipose tissue and blood plasma. And then the data obtained from preclinical studies to predict the unknown and unobserved processes (fluxes, species, time points) can be integrated in the model.

Furthermore, we can even simulate possible treatments and interventions and explore their effects. In this case of the Metabolic Syndrome, especially the balance between energy intake and energy consumption (through e.g. exercise and heat production) is important. Recently much attention has been paid to the activity of so-called Brown Adipose Tissue (BAT), which possesses the ability to produce heat under e.g. cold exposure. But there are other ways to stimulate energy expenditure: BAT can also be activated via pharmacological targeting. This seems a promising target to combat obesity and its related diseases, and is one step closer to finding out which processes we should target to reverse the Metabolic Syndrome back to a healthy state.