The ISBGroup Blog

The ISBGroup Blog

About the blog

Here you can read about everything that's happening in the ISB Group.

New M.Sc thesis presentation: Niclas presented his work about multi-level and multi-scale modelling in rodents

NewsPosted by Niclas Bergqvist Fri, June 16, 2017 13:05:24

Last Wednesday (14/6) I presented my master thesis entitled Multi-level and Multi-scale Modelling: From Adipose Intracellular Insulin Signaling to Whole Body Metabolism and Weight Alteration. This presentation included a brief explanation of all my work here as a part of ISBGroup. I started my journey here as an intern already in the summer of 2015 following the bachelor course. Back then, I worked with a project involving the development of a model describing the intracellular signalling chain in rat adipocytes. The internship lasted for two months, but the project went so well, that I decided to continue the work alongside my studies. One and a half year after the start of the internship, the project successfully resulted in a published article. Around that time, I was supposed to start writing my master thesis, so it felt natural to continue on this track. So, by using the newly developed intracellular model as a base, I continued the development towards a first multi-level and multi-scale model in rodents. The abstract from my master thesis is attached below.

Type 2 diabetes, T2D, is a prevalent, costly disease that affects millions of people worldwide. It is a complex metabolic disorder which is characterized by insulin resistance. The resistance is believed to initially arise from adipose intracellular malfunctions and later spread to adjacent tissues, eventually affecting mechanisms on multiple body levels. To handle this complexity, mathematical models has been developed through systems biology modeling. These include models, in both rodents and humans, that describe mechanisms on single body levels, as well as more advanced models that describe T2D associated mechanisms on multiple levels. However, these multi-level models have so far mainly revolved around humans, and no such model focused around diabetes in rodents has yet been developed. Animal models possess many benefits, like processing valuable animal data that is difficult to obtain from human experiments, or act as replacement for test-animals. For these reasons, a first multi-level and multi-scale rodent model has been developed that describe mechanisms on multiple levels; from the intracellular level (the adipose insulin signaling chain from the insulin receptor, IR, to the GLUT4 transporter) to the whole-body level (including the glucose-insulin metabolism and weight change). Experimental data was obtained on these various levels, and used to improve and test the model. The intracellular section of the model was created through a connection of two existing models and can describe over 140 experimental data points. It was also validated with independent experimental data and was used to form predictions about the relative contribution of the pathways from IR to GLUT4. The new multi-level model was developed after new connections was established between this intracellular model and a model describing meal responses over a couple of hours, as well as with a model describing weight change over days and weeks. The resulting multi-level model have created insights to what mechanisms are necessary in order to simulate data on all levels. The model also aims to increase the mechanistic understanding of T2D and eventually provide a contribution to the drug development process, by reducing the amount of animal trials and increasing the success chance of the developed drugs.

- Niclas Bergqvist