The ISBGroup Blog

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

As part of the collaboration with ”Forska Utan Djurförsök” (The Swedish Fund for Research without Animal Experiments), ISB group is going to Almedalen in July. Almedalen is the biggest political event of the year in Sweden, and Gunnar Cedersund has been invited to participate in two events:

* Monday July 3, 13-14.30 in Maltfabriken. Then Gunnar and a few others will give short initial presentations, followed by a panel debate with politicians, and ended with some hands-on tutorials, by some of the students from ISBgroup. If you want to try to simulate our own models for diabetes, you should come then. (link to more info)

* Thursday July 6, 10-11.30 in Maltfabriken. Then a short introduction will be followed by a longer session with hands-on testing, not only regarding mathematical models but also regarding other experimental alternatives to animal experiments. The focus then is on chemicals and cosmetics testing (involving e.g. the qsar model). (more info)

Apart from these two events, Forska utan djurförsök will also have a final opportunity to come and talk with them on Friday July 7, at 10-11.30 in Maltfabriken. This will be a more informal event, with the opportunity to come and talk and have coffee with people who know a lot about these issues (link).

Welcome!
Karin for ISBgroup

There is a workshop upcoming about modelling of biological systems at Linköping university. It will take place Thursday-Friday this week, May 11-12, 2017, and is open to everybody who wants to attend: students, scientists, and the general public. We will contribute with one presentation, at Thursday 16-16.20. This presentation will consist of an overview of our modelling philosphy and of our various modelling projects. Apart from us there will be some 20-25 other groups who will present as well. Almost all of the presenters either still work, or have worked, at LiU, i.e. Linköping university.

More information about the workshop can be found here.

Last Friday, one of our Ph.D. students – Mikael Forsgren – nailed up his Ph.D. thesis on our local thesis tree. He thus followed in the footsteps of many many others, ranging back possibly even beyond Martin Luther, by thus publically announcing that he has something that he would like to publically discuss: the thoughts and results in his thesis.

The formal defense will be held at 13.15 in Eken, at HU, Linköping, Sweden. The opponent will be Stephen Sourbron, from Leeds, who is an expert on perfusion modelling in different organs. Mikael’s thesis is about modelling of not only perfusion, but also of intracellular uptake and release, concerning the contrast agent Primovist. He shows how the estimation of such uptake properties using mechanistic modelling can be used to obtain new patient-specific biomarkers, which can be obtained from MRI examinations, and which thus can move to eventually become a non-invasive replacement for today’s invasive liver biopsy examinations. The goal is that this should lead to a reduction in healthcare cost and individual suffering, and to an increase in accuracy and diagnostic power.

Welcome!

Last weekend in Norrköping, ISB Group enjoyed a spring event to help incorporate future members and bring the group even closer together. The event started on Friday with vivid discussions at the Worker’s Museum. Gunnar Cedersund also presented his vision of the future; and how ISB Group is apart of it.

The group also experienced several well-deserved fika breaks, a fine Italian dinner at Enoteket and wrapped things up with a battle of wits at the riddled Escape Room. We hope everyone enjoyed themselves as much as we did, and thank everyone for showing up. Special thanks to the event coordinators.

ISB Group

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.