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

Student presentations – an overview of our systems biology projects

Events Posted on Thu, May 28, 2015 08:42:30

On June 1, our annual project course – the Bachelor’s course for the ~30 students in Engineering Biology, TBMT33 – is having its final presentation day. This is a good chance to get a quick overview of existing projects within ISBgroup, and to see some of the different ways that mathematical modelling can be used as an integrated tool in experimental and clinical research. The schedule of the day is as follows.

All presentations in Linden, Campus US
8.15-9: Master Thesis presentation, “Quantitative translation of drugs’ effects on type 2 diabetes mellitus: from diabetic rodent models to patients”, Philip Blomström. Supervisors: Elin Nyman and Monika Sundqvist, Project done at AstraZeneca

9.15-9.45 “Intracellular insulin signalling and mechanisms of adiponectin release”. Supervisor: Rasmus Magnusson. Collaborating groups: Peter Strålfors (IKE), Cecilia Brännmark (Gothenburg Univ).
9.45-10.15 “Improvement of a Mathematical Liver Model for Diagnosis and Surgical Planning”, Supervisor: Markus Karlsson. Collaborating group: Peter Lundberg (IMH/CMIV)

10.15-10.30 Break

10.15-10.45 “Multi-level and multi-time scale modelling of glucose homeostasis disorders: monitoring in ICU and obesity drug simulations”
Supervisor: Andrea Hjelm. Collaborating groups: Peter Strålfors (IKE), Peter Gennemark (AstraZeneca), Folke Sjöberg (IKE)

10.45-11.15 “Modelling the BOLD response in fMRI”
Supervisor: Karin Lundengård. Collaborating group: Maria Engström (IMH/CMIV), Fredrik Elinder (IKE)

11.15-11.45 “Understanding desensitization – by examining cardiac myocytes and sensory neurons”
Supervisors: William Lövfors and Rikard Johansson. Collaborating groups: Jordi Altimiras (IFM), Claudio Altafini (ISY)

12-13 Poster presentations of all projects outside of Berzelius.

Questions and more info: Gunnar Cedersund, gunnar.cedersund@liu.se

Welcome! 🙂



Kicking off the new year

News Posted on Mon, February 02, 2015 16:50:22

2015 looks like it is going to be a good year for us, starting with two publications:

* Dominant negative inhibition data should be analyzed using mathematical modeling – re-interpreting data from insulin signaling.

* Mathematical modeling improves EC50 estimations from classical dose-response curves.

We celebrated this and the start of the new year with an after work kick off at De Klomp in Linköping

ISB Group at after work at De Klomp. January 2015.



6th Swedish Meeting on Mathematics in Biology

Events Posted on Wed, December 03, 2014 10:58:06

On Thursday and Friday, the 6th Swedish Meeting on Mathematics in Biology takes place in Linköping.

We will be there and do a small presentation of our work. Hope to see you there!



A BOLD half-time

Events Posted on Fri, November 21, 2014 23:04:42

Karin Lundengård just did her half-time, and it’s on youtube!

“My research project is on the activity of the human brain. The activity can be measured by functional Magnetic Resonance Imaging, which measures the Blood Oxygen Level Dependent (BOLD) response. As the name states, it is the oxygen levels being measured, but they are connected to the electrical signaling of the neurons via the neurovascular coupling. There are several hypothesis about the underlying mechanisms of the neurovascular coupling and here we have used mechanistic dynamic models to investigate two of them. So go have a look at the video to see how it went!”

Hopefully the article will be submitted for press before Christmas.

Karin Lundengård
PhD student at IMH and CMIV



NBC16 & MTD10

News Posted on Fri, November 21, 2014 22:57:49

Recently,
I made a short visit (only the first day) to the joined conferences
16th Nordic-Baltic Conference on Biomedical Engineering and Medical
Physics and 10th Medicinteknikdagarna in Gothenburg to present our fMRI
model in the neuroengineering session.
It was a small but rather well attended conference with a leisurely
tempo that gave ample time for discussions. There were several
researchers form Linköping present, although not from our group.
Unfortunately most of us were placed in the same session and
although I found Haj-Hosseinis talk about ”Photodiagnostics in Brain
Tumor Surgery”, Dunås talk about ”Towards automatic identification of
cerebral arteries in 4D flow MRI” and Latorres talk about ”Paxon: The
Physical Axon Model” interesting, I had heard them
before.

Most inspiring during the day were two different presentations: the
first was the plenary session where Dremstrup spoke about ”Technology in
the rehabilitation after stroke” and showed how they had identified the
right point in time and space to deliver a small
electric chock to nerves in the foot or hip in order to help stroke
patients walk again, and the second was ”Human stem cell neuronal
cultures and activity – from 2D to 3D” with the finnish researcher
Hyttinen who experimented on neuronal stem cells growing
in a 3D matrix. The latter is something that is highly interesting for
our research as it investigates the actions of the astrocytes in the
brain.

My presentation was well received and led to interesting discussions
afterwards, most notably with Hyttinen and later with a medical doctor
who proposed TENS for stimulation of brain areas.

Karin Lundengård
PhD student at IMH and CMIV



A road trip to Trondheim

Events Posted on Mon, November 17, 2014 14:54:10


Can anything be nicer than combining work with a trip to
Norway? – Probably, the pizza was as expensive as the myths foretold.

Joking aside, during the field trip to the conference
Virtual Physiological Human in Trondheim, a summit to discuss multi-level
models representing human physiology, the ISB group once again got a chance to
display its work. With the help of several presentations, both oral and
posters, new contacts were made and there was much rejoicing!

As a student visiting such an event for the first time, one
cannot help but feel a bit lost among the field leaders and other experts. I
can also admit that I was pretty nervous about my own poster presentation, but I
started to relax some time into the poster session.

To sum up the trip: Making new connections and getting out
our research is enjoyable, eating pizza in Norway, not so much.



Summing up 2013

Yearbook Posted on Mon, November 10, 2014 14:46:00

2013 continued on the new and higher level we had achieved in 2012, and continued to expand from there. We sent two people to Merrimack, we got a new Ph.D. student, we had even more people at ICSB, and we published our probably most important paper to date.

* In the spring of 2013, we did a new version of the annual course TSRT17: Systems biology modelling project. This involved around 35 students from the biomedical engineering programme (TB) and the industrial engineering biotechnology profile. As usual the projects dealt with real-life problems from different research groups, who gave the students real unanswered biological questions, which only can be answered via the usage of mathematical modelling. The students were divided into 6 projects, who worked with i) the understanding of heart desensitization, ii) insulin signalling and lipolysis in adipocytes, iii) facilitation in neurons, iv) myelin-measurements from MRI brain scans, v) estimation of liver fibrosis based on MRI time-series, vi) cell-to-cell differences in yeast cells. Group ii) did their work as a B.Sc. project. As previous years, we had a logotype-competition, and below you see a picture of the winners of their logotype.


* As usual, we recruited some of the most talented students from the course, to work in our group in various types of student projects, usually with associated scholarships. Some of these student include Philip Blomström, who worked with facilitation in neurons, and Mattias Köpsén, William Lövfors, and Fredrik Söderquist, who worked together with us, Mika Gustafsson and Mikael Benson to develop a method to estimate mechanistic ODE-models from omics data.

* We also had some older students around, and some of these were also on their way out towards their future careers. As illustrated in a previous blog entry, Linnea Bergenholm and David Janzén visited Merrimack Pharmaceuticals in Boston for a 6 month internship. This then led them to positions as Industrial Ph.D. students at AstraZeneca. This recruitment process illustrates the competitiveness of students who have been trained in our group: 2 of our students applied, both got the position. Apart from this, David Jullesson worked with the finishing of his paper, which then led him towards a Ph.D. position on Synthetic Biology with Jens Nielsen in Gothenburg. David also started up Linköping’s participation in iGEM, an international undergraduate synthetic biology competition. In this project modelling was used to some extent. Finally, Markus Karlsson worked during the entire spring semester with the application of the nonlinear mixed-effects modelling software Monolix to our liver model: this showed that our model-based approach outperforms all other image-analysis approaches, when it comes to generating biomarkers that can predict liver fibrosis.

* 2013 was also the year when a new Ph.D. student started: Mikael Forsgren (picture above). He had already been around for several years, working on modelling and experiments on the liver, and had just started a position at Wolfram MathCore, as a consultant in modelling. This Ph.D. position meant that we got him back as a 50% industrial Ph.D., and that we further strengthened our collaboration with MathCore.

* 2013 also saw the publication of our perhaps most important publication to date: our multi-level explanation to the origin of insulin resistance. In this paper, we had complemented our existing data for insulin signalling with new experiments, to get a first collection of systems-wide time-series and dose-responses for the main players in the insulin signalling network, both normally and in type 2 diabetes (examples in sub-figure A above). These unique data allowed us to, for the first time, test existing hypotheses regarding the origin of insulin resistance, i.e. the malfunction in the insulin signalling network seen in type 2 diabetes patients. We could then show that a specific feedback, from the protein mTORC1 to the protein IRS1, is a potential such explanation. If the network is perturbed in this feedback (red arrow, sub-figure B), the entire network switches from normal to diabetic signalling. This model has since its publication gained a lot of interest from pharmaceutical companies.

* Several of these showcases were presented at large international conferences, most notably the International Conference for Systems Biology (ICSB). ICSB was this year held in Copenhagen, and we went down with the largest group yet: around 15 people from at least 4 different research groups were present from Linköping. We were also well received, and Linköping had three oral presentations: Robert Palmér from the spin-off company MathCore presented our joint story on understanding the T2D drug Anakinra, Gunnar Cedersund and Markus Karlsson presented the above mentioned story on liver diagnosis, and Mikael Benson – not from our group, but also from Linköping – gave a keynote lecture on clinical end-usage of systems biology.

All in all, this year demonstrated that the previous successes of 2012 were not a one-time luck, but that we could sustain this level of activity and international visibility, and thereby bring high hopes for the coming year of 2014.



Summing up 2012

Yearbook Posted on Sat, March 01, 2014 14:13:22

2012 was the year when the core facility started to take shape as a separate unit. This had been a long-time dream of mine, and when I (Gunnar Cedersund) in 2011 was awarded a VR FoAss, I could slowly start the process of building up such a joint modelling environment, working as a common knowledge and computer resource and as a physical meeting place for all groups and people wanting to do mathematical modelling of biological systems.

The part of the group that went down to SBMC in June 2012. Above, from left: Patrick Weber, Rikard Johansson, Karin Lundengård, Mikael Forsgren, Gunnar Cedersund, Linnea Bergenholm, David Janzén, Magdalena San Roman, Elin Nyman. Front, from left: Zaheer Ali, David Jullesson.

Here are some of the more specific highlights:

* During the spring and summer, we had two external visitors: Patrick Weber from Stuttgart, who came to experience work in applied research and to contribute with his knowledge about Bayesian methods for parameter estimation, and Magdalena San Roman from Montevideo, Uruguay, who came to learn our type of modelling, but also to share her knowledge about metabolic control systems. They are both depicted on pictures below, and they both entered into different ongoing projects here, including in a joint project on new improved methods for sensitivity analysis with uncertainty.

Patrick Weber, our visitor from Stuttgart, Germany

* During the spring, Eva-Maria Hansson, who had previously worked and done her M.Sc. thesis with us, went to visit Merrimack Pharmaceuticals in Boston, US. She was therefore the first student, who initiated a tradition and collaboration between SBCF and this company: we train really talented students in the wonderful art of systems biology, and when they are finished, we each year send some 1-3 of these students to work in internships for them. These internships are payed employements where you do modelling in pairs with an experimentalist at Merrimack, together with which you test out a new idea for a drug or a biological mechanism. If the project turns out to be promising, they will take it further, and – with some luck – the results will one day form the basis for a new drug or treatment.

* During the year, we also had some internal M.Sc. students who finished their projects for us. For instance, Linnea Bergenholm, who had already been working for a year with us prior to her thesis (mentioned here), and Zaheer Ali, who initiated the work on facilitation, that we presented in Liepzig (mentioned below). Another Ph.D. student was David Janzén, who worked on usage of mixed-effect modelling for estimation of noise and for analysis of cell-to-cell variation.

* In June, we attended the bi-annual conference Systems Biology of Mammalian Cells (SBMC), in Leipzig. SBMC is probably the second biggest conference on systems biology, and the focus fits our research very well. We went down 11 people in two big rented cars/vans, and spent 4 days in what I will probably for a long time consider as the defining trip – as the trip that defines the ultimate group trip. That was not only because we were a number of people who had started to grow together over the years (see the picture above), but also because we made such a big overall impression on the event: we had 3 oral presentations, and I was chair for one of the sessions. This probably made us the most well-represented group at the whole event! The three talks are available as videos, and were given by Elin Nyman (who spoke about her recent paper on insulin signalling in rodents), Karin Lundengård (who spoke about modelling to unravel the mechanisms behind facilitation in neurons), and Mikael Forsgren (who spoke about our clinically useful modelling on liver diagnosis).

Our guest Magdalena San Roman, who took a beer at SBMC together with Jan Hasenauer, who was a previous guest of ours, from a few years earlier.

* In August 2012, I also – at last – published a paper on the set of methods for core prediction analysis that I had presented on posters and presentations for several years (it was also an invitated paper, following my talk on ICSB the year before). This was the presumably most important paper of that year, and it forms the basis for many future systems biology papers, both on methods and on applications in various fields. However, some other papers worth mentioning are this paper on describing large-scale networks in a manner consistent with modelling (developed together with our guest professor, Hiroaki Kitano), this review on modelling of insulin signalling, and the insulin signalling paper Elin Nyman presented at SBMC (video link above).

* Following these developments done during the first half of the year, on Sept 24 2012, we were finally ready to declary ourselves as an independent group. This date is henceforth referred to as the SBCF day, the day our systems biology core facility was officially launched.

Picture of Karin Lundengård, our new Ph.D. student.

* 2012 was also the year when Karin Lundengård started her Ph.D. with us. In practice she had been around since her M.Sc. thesis about a year earlier, but now we had gone through all the steps of finding money, supervisors, and the formal process of announcing positions etc. Karin is having me as co-supervisor: her main supervisor is Maria Engström, and her other co-supervisor is Fredrik Elinder. Fredrik has experience of both modelling and experiments on neuronal cell-biology and electrophysiology, and Maria is an expert on fMRI, used to investigate brain activity. Karin will in her thesis combine these levels, and provide a more mechanistic understanding for the data that can be obtained from fMRI, and thereby get more information from the data, eventually leading to better usage of the technique, and to better understanding and treatment of diseases like narcolepsi.

In Dec of 2012, Cecilia Brännmark graduated from her Ph.D. studies. Here we see her during the ritual known as “spikning”, where she nails her thesis to the “thesis tree”, seen to the right.

* At the other end of the spectrum, 2012, was also the year when our first Ph.D. student graduated, i.e. finished her Ph.D. studies. The student, Cecilia Brännmark, was the first one I (Gunnar) supervised, and she started back in the days when I did all the modelling myself. Hence, Cecilia was an experimental Ph.D. student, and she has done the majority of the experiments in the early defining papers, that came out of my collaboration with prof Peter Strålfors, who was her main supervisor.

* In December we arranged a 10-day Ph.D. course on Multi-level modelling of gluocse homeostasis. During these 10 days we had invited the most relevant and world-leading experts on systems biology research on all the main organs: the liver, fat tissue, skeletal muscle, the brain, the pancreas, and the whole-body level. For all these organs we had invited experts on both the experimental research and on the modelling.

* As a separate event in the middle of this course, we also arranged a workshop on Systems Medicine. This was a co-arrangement with Mikael Benson, who arranged the first day devoted to omics and large-scale network approaches, and isbgroup/me, who arranged the second day devoted to modelling. In other words, we tried to bring together all the different sides that are relevant to systems medicine, and regarding the modelling this importantly included the neighbouring biomodelling fields, such as pharmacokinetic/pharmacodynamic modelling, image-based modelling of the liver, medical decision making with probabilistic graphical models, and even an overview of the neighbouring research in technical diagnosis. At the event there was also a strong presence from several leading drug development companies. The event was atteneded by some 60-80 people, and the combined 10-day event was the – by far – biggest arrangement we had arranged at that point.



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