The ISBGroup Blog

This autumn, we welcome another new student in our group: Thea Sandqvist

Hi!

My name is Thea and
I’m here in the ISB Group to do a project in systems biology for my 6th semester in Medicine.

My project is about insulin- and
glucose metabolism in rodents switching between chow- and high fatty based-diets. The project is based on a multi-level-multi-scale model
conducted by former ISB Group-member Niclas Berqqvist. My experimental data
comes from Karin G. Stenkula and her research group in Lund.

Besides spending time at the office I enjoy an occational pain-au-chocolat (or two or five).

This Wednesday I nailed my thesis outside the C2 lecture hall at campus Valla. It was a peaceful, quiet and beautiful ceremony.

Tomorrow, Friday the 13th, I will nail a second copy at IMT, with a bit more pomp and circumstance.
Welcome to “spika-fika” at 14.45 at IMT, campus HU if you want to join for some cake.

You can find my thesis online:
https://doi.org/10.3384/diss.diva-141614

This autumn, we welcome a new student in our group: Valentin
Kindesjö

​Hello! My name is Valentin Kindesjö. I started medical
school at Linköping University in the spring of 2015 after studying a year and
a half of biomedical engineering. For the autumn of 2017, I have found my way
back to IMT to join ISB group for a project in mathematical modelling, where I will
be continuing the work of previous students (most recently Johanna Fridberger
and Thirza Poot) in expanding a multi-level model over the regulation of
glucose, insulin and fatty acids, created by joining a glucose- and insulin
model created by Dalla Man et al and a NEFA model, created by Jelic et al as an
expansion on a model by Fianne Sips. I will be working to make the NEFA part of
this model more physiologically correct. Hopefully, this work will bring us
closer to finding out the exact role played by adipose tissue in maintaining
the systemic energy homeostasis, and shed some light over the dynamic interplay
between the different mechanism involved in the storage and release of fatty
acids.

I am spending my autumn in Oxford, at the group of Fredrik
Karpe, professor of metabolic medicine at the Oxford Centre for Diabetes,
Endocrinology and Metabolism, who conducted the experiments where the data I
will be using was collected.

Cardiovascular disease (CVD) is one of the most life-threatening conditions of our time and one with limited treatment options for severe cases. Improved diagnostics and preemptive treatment methods are thus especially important. Fredrik Eklund’s thesis, labelled “Guided Bayesian Graphical Network model for Cardiovascular Disease Prediction”, continues the work towards a tool aimed to provide decision support for medical practitioners.

Bayesian Graphical Networks (BGNs) are prominent decision components in the field of machine learning and artificial intelligence. A strength lies in their ability to infer partially missing data using its distribution and other data, i.e. from the same patient. This is a powerful feature in clinical practice because some informative measurements may be costly or invasive to obtain.

The thesis report suggests rules to model BGNs by in order to battle issues with high dimension clinical data as well as to reflect the pathophysiology of CVD. An algorithm was then developed to build BGNs according to these rules. Following these two steps, a BGN to predict CVD was built from clinical data on type 2 diabetes patients. The result is a network which joins prior knowledge with machine learning techniques. The network can be considered a proof of concept and a mild success.

According to agreement with Gunnar Cedersund, Fredrik Eklund will continue work on the model in the months to come.

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

This spring, we welcome a new student in our group: Thirza Poot

Introduction:

Last
spring, I finished my third year of the Engineering Biology study program at
Linköping University with a bachelor’s project within systems biology. After
this, I decided to take a break from the study program in Linköping to study in
Vienna for the winter semester 2016. Recently, I returned to Sweden, and have
decided to join ISB group for another project within system’s biology!

In the
bachelor’s project, I worked with two models regarding glucose concentrations
in critically ill patients admitted to the intensive care unit (ICU). This
semester, I will instead work with models regarding the interplay between non-esterified
free fatty acids (NEFA), glucose, and insulin, and their connection to obesity
and type 2 diabetes. The goal is to also investigate if and how these models
can be adapted to the ICU.

Earlier this month I attended the annual meeting of the European Society for Magnetic Resonance in Medicine and Biology. At the conference I had the opportunity to giva a presentation of a part of my thesis project. In this part of the project, we’re using mechanistic modelling of data from contrast enhanced magnetic resonance imaging in order to get biomarkers that can quantify liver function. The idea is that our biomarkers should be used by physicians, e.g. when planning liver surgery.

/Markus

Picture of me presenting.

During the autumn we have three new students in our group
Nicolas, Fredrik, and Johanna: The latest students to join our group.

Here’s their introduction

Nicolas

I’m
a student at Linköpings university, studying for a masters of science in
engineering biology, I have finished my third year but have decided to take a
break to work as an intern at the ISB group.

The
project I’m involved with at the moment revolves around studying the regulatory
mechanisms that control the antioxidant levels in the body. Antioxidants are
generally believed to be unregulated and simply accumulate upon continuous
intake and such an accumulation could help explain the many health benefits
observed when eating antioxidant rich foods. However this accumulation has
never been observed for more than a few hours after intake. The results of
previous studies show that there is reason to believe that the antioxidant
levels are regulated by homeostasis. The purpose of this project is to use
systems biology to investigate the regulatory mechanisms involved with
antioxidant metabolism and see if there is a homeostatic regulation of the
body’s antioxidant capacity. This project will continue and expand upon the
project I did for my bachelor thesis in the spring of 2016 where I investigated
the regulatory mechanisms that control the antioxidant capacity (AOC) in the
cytoplasm and used mathematical modelling and prediction analysis in order try
to predict how the AOC levels would change after a single dose of antioxidants
are given to a test subject. At my disposal i had access to data collected from
experimental studies conducted at Newcastle university. With the results from
my bachelors project I was able to provide the team in Newcastle with a decision
basis for how to design a new experimental study which they conducted in the
summer of 2016. I will use this data, collected from the latest study in
Newcastle to continue investigating how antioxidant capacity is regulated and
also investigate how different test subjects react differently using nonlinear
mixed-effect modelling.

Fredrik

My
name is Fredrik Eklund and my background lies in bioengineering, with a focus
on materials and biosensors. I’m currently working on my master’s degree thesis
in the field of systems biology, however. The project I’m involved in is a
continuation of previous students’ work on a statistical heart attack model. It
is a predictive model meant to be used as decision support by doctors. In its
core, a Bayesian network is trained to understand relationships between a large
number of parameters. The trained network is then used on a new patient’s
measurements for prediction. Based on the result, a medical practitioner can
then take the appropriate course of action.

Johanna
My name
is Johanna Fridberger and I am a new member of the ISB group. I will be staying
for one semester conducting a project on the model developed by Fianne Sips described
in the article ”Model-Based Quantification of the Systemic Interplay between
Glucose and Fatty Acids in the Postprandial State” in which I will exchange the current NEFA (Non-Esterified Fatty Acids)
part of the model to one that better describes physiological conditions. This
is possible thanks to new data on NEFA homeostasis. I am doing the project as
part of my education in medicine at Linköping University, now reaching the end
of the third year. I have really enjoyed working in this group so far, and I am
excited over the next couple of months here!