Archive for December, 2015

8 December 2015

Jan Boren (University of Gothenburg, Sweden) about his role in the RESOLVE consortium

  • What is the expertise / knowledge that you bring into the RESOLVE project?
    We have a long history of studying metabolic diseases, including type 2 diabetes and fatty liver. Most of our research has focused on lipids and lipoproteins . Our expertise includes assembly and secretion of lipoproteins in the liver, lipoprotein metabolism and regulation in the blood, mathematical modeling of lipoproteins, stable isotope labelling and molecular lipid analyses.
  • What is your role in the RESOLVE project and why is your data relevant for the consortium?
    Our role is to provide data, both by previous and ongoing studies, of how lipoproteins circulate in the blood. These data provides a fundament on which more complex models can be built.
  • What are the challenges, in your opinion, in the project?
    The most challenging task is to generate the right data, at the right time, that is needed to build the models. Data generation, in particular data from humans, takes very long time and it may be too short time for the modelers to build models based on the data.
  • How can RESOLVE help your research?
    RESOLVE impact our research directly, as development of models allows us to investigate exactly the research questions that are in our primary interest. That is; how the lipid metabolism is regulated and modified by interventions.
  • How do you think, can system approaches help your research?
    Building from our own and others research it is easy to draw a cartoon, a schematic picture, of how things are connected. We may draw lines that connect our favorite molecules and organs. However, when it comes to understand how strong these relationships are in reality things are not so easy. We may have derived our findings from cells, mice models, genetic diseases or observations in humans.
    By building mathematical models it is possible both to verify the existence of the connections, but also to quantify how strong (and relevant) the connections are.
  • How close is your science to the community and patients with the metabolic syndrome?
    Our research is very close to the patients. For the last decade we have focused our efforts on understanding how lipid disorders appear in the metabolic syndrome. Most of our study subjects are individuals with the metabolic syndrome.
  • What are, in your opinion, directions of decisions that are vital to the progress of systems medicine?
    Firstly, we think that systems medicine will be an important corner stone in the future of medical research. For systems medicine to gain traction we believe there are several critical decisions to be made:

    • To many researchers the use of models, equations and special computer software are not easy. Software with a low entry threshold and with out of the box functionality is needed.
    • Comprehensive databases and model collections are needed. Today researchers need to draw data from several sources, using different formats and versions.
    • Many technical hurdles still exist. It is too early to start to focus on particular solutions and/or techniques. For instance, time scales (body weight changes in the scale of years vs hours for blood lipids) and amounts (10’s of kilos of body fat vs grams of blood lipids) needs to be combined with spatial scales (organ, tissue, cells) and blood flow models. Likely, models needs to be described on different levels for different research questions.
    • More research is needed on how to solve computational challenges that arise in biological systems. Uncertainties are present in the measurements as well as in the models. Biological variation is having a large impact on results and new approaches to combine mathematical and statistical models are needed.

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.