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The ISBGroup Blog

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

Upcoming lecture in new European webinar series on 3R, Sept 22-24

3R and animal experiments, Events, News Posted on Sun, September 06, 2020 22:56:51

A new international webinar series on 3R – replacement, reduction, and refinement of animal experiments – is about to start! And we are present with a lecture!

From our group, Gunnar Cedersund and Elin Nyman are members of the National Committee on 3Rs, which also serves as the steering committee for the Swedish 3R center (S3RC). Our S3RC has now joined forces with a few other corresponding national centres, and this has led to the launch of a new webinar series. The first edition of this will take place on Sept 22-24, lunch times i.e. 12.30-13.30 CET. Gunnar will present a lecture on digital twins on the last day, i.e. Sept 24.

This is a great initiative, and I hope it will be the start of more collaborations between the centres!

More info, and sign-up here.



Upcoming Ph.D. defense, Sebastian Sten, “Mathematical modelling of neurovascular coupling”

Events, News Posted on Sat, September 05, 2020 01:59:22

https://www.youtube.com/watch?v=OTvhkYVhq5Y&feature=youtu.be

On Friday, this coming week, September 11, 2020, at 9AM CET, our Ph.D. student Sebastian Sten will defend his Ph.D. thesis, entitled “Mathematical modelling of neurovascular coupling”.

Sebastian has been co-supervised between Gunnar Cedersund (who leads this group), Fredrik Elinder (BKV and electrophysiological expert), and Maria Engström (who was the main supervisor, and who is an expert on fMRI). In the thesis, Sebastian presents four papers which incrementally unravels more and more mechanistic details of how the main signal in fMRI – the BOLD signal – is generated. In Paper 1, he demonstrates that the main part of the BOLD signal response can not be caused by a negative feedback, as was first believed, but by a combination of a fast positive and a slow negative feedforward arm. In Paper 2, the model from paper 1 is extended with GABA, which makes it able to describe the negative BOLD response. In Paper 3, he unravels more mechanistic details of the two arms, and finds out that there are in fact at least three arms: the fastest positive is the NO-arm from interneurons, the slightly slower positive arm is the PGE2 arm from pyramidal cells, and the slowest negative arm is caused by NPY interneurons. In the final paper 4 (still in ms), these mechanistic details for the signalling and the control of the arteriolar diameter is embedded in a larger model, which also contains the biomechanical flow to capillariies and venules, and the creation of the actual BOLD signal. The final model is – to the best of our knowledge – the most complete and comprehensive model for the BOLD signal, and it simultaneously describes data and extracts information from informative optogenetic stimulation experiments in mice, from unique BOLD and Local Field Potential (LFP) experiments in monkeys, and from advanced MRI measurements of BOLD, volumes and flows, in humans.

Front page of the thesis, illustration done by our other group member Christian Simonsson, who wanted to capture not only the brain, but that experiments, analysis, and mathematical modelling has come together.

Overview of the main processes studied in the thesis.

After the defense, Sebastian will work for two more weeks, wrapping up the final paper. Thereafter, other people in the group will continue to work on these models, e.g. by connecting them to more detailed models for metabolism, electrophysiology, and – eventually – to clinical practice, e.g. by allowing for more measurements to come together into a more comprehensive and complete analysis of fMRI data. However, Sebastian himself will thereafter start a position at AstraZeneca, in the group we have the most contact with there: their metabolic and cardiovascular preclinical modelling group.

A link to the Ph.D. thesis is found here, and a link to the youtube event where the defense is broadcasted is found here.

Sebastian about to do the final formal step before the actual defense: nailing his thesis to the “thesis tree” of the medical faculty.



Presentations at the VPH Virtual Physiological Human conference

3R and animal experiments, Events, News Posted on Sun, August 30, 2020 01:43:23

As usual, we have attended the Virtual Physiological Human conference, which this year was given as an eConference. This year, our group was represented with two oral presentations, and three poster presentations. The first oral presentation was held by Gunnar Cedersund, with the title: “Multi-organ and multi-level digital twin models enters the clinic”, and it was similar to the presentation already held at numerous earlier occasions, e.g. at Almedalen, in the Swedish Parliament, at NIH, etc.

Screen short from Peter Gennemark’s presentation at the VPH conference

The second presentation was of a new project: Belén Casas’ postdoc project on modelling of microphysiological systems. This project is financed by AstraZeneca, who are the ones who do the experiments, in collaboration with the company TissUse. This modelling has allowed us to both understand the available system better, and to create a first translation up to humans. This brings us one step closer to finding a workable replacement for animal experiments regarding research on type 2 diabetes and Nonalcoholic SteatoHepatitis (NASH) in the liver. The postdoc project has been supervised by Gunnar Cedersund and Peter Gennemark (AstraZeneca, but also adjoint associate professor in our group). Since Belen is now away on parental leave, Peter gave the presentation. The three final poster presentations were on digital twins and multi-level modelling (Tilda Herrgårdh), on modelling of fatty acid fluxes in the fat tissue (Kajsa Tunedal), and on a new model for exercise (Antonia Klingsäter). Apart from our own presentations, it was interesting to see that the new ASME V&V40 guidelines from FDA, on usage of modelling in certification, are getting more and more traction. Another interesting presentation was the keynote held by Tarique Hussain, who talked about how he has been using advanced modelling of the heart, to help guide treatment planning of complicated cases in child cardiology.

Screen short from the presentation by Tarique Hussain


Precise4Q meeting in Linköping

Events, News Posted on Tue, November 12, 2019 16:02:17

During 7th and 8th of the November, we have had meeting with our partners in the PRECISE4Q project here in Linköping. In PRECISE4Q, we are working wit developing hybrid models for a decision support for Stroke treatment together with scientists within health informatics, computer science, machine learning, medicine, etc.

During the meetings, we discussed our upcoming EU review (we are financed by EUs Horizon 2020 project), how we should move forward in general, and met with local scientists here in Linköping that are working with similar things.



New PhD student

News Posted on Wed, November 21, 2018 13:20:01

Hello!

My name is Tilda and I have been in the isb
group before, but this November I started my phd here. I am financed by an EU
project called precise4Q. The project aims at personalising treatment of stroke
by developing model-based decision support systems. I will be working with combining
mechanistic multi-level models and machine learning models.



New money, from VR, SSF, H2020, and AstraZeneca

News Posted on Sun, October 28, 2018 16:57:59

We have gotten money – and lot’s of it!

While on a 6h train ride between Malmö and Stockholm, I at last have time to share some of the good news that have come to us, one after the other, but that I haven’t had the time to share with you here until now. The good news is that we have had a series of successful grant applications, which mean that we now have reached a whole new level, in terms of money flows, and that our group will significantly grow in the next 2-3 months.

This new money
flow actually started about a year ago, when I got money for a new 2
year postdoc position from AstraZeneca, i.e. approx 3 MSEK (300 000
USD). In this postdoc, we will create models for a new type of
animal-free experiments, called organ-on-a-chip. In this technique, you
build a system of realistic 3D organs made up of human cells, which are
interconnected by an artificial blood flow. This is a supercool
possibility, which is ideal for both modelling, for replacing animal
experiments, and for understanding diseases.

This grant was then
followed by a new EU project, called PRECISE4Q, which was approved in
January this year. In this project, we will make use of our multi-level
mathematical models for diabetes and cardiovascular disease, to create a
new clinically useful tool. The basis of this tool will be quite
general, and applicable to a wide range of diseases, but the focus will
be on helping patients who have or who are at risk of suffering a
stroke. The total budget of this project is 60 MSEK (approx 6 million
USD), and of that approx 4 MSEK goes to my group (400 000 USD).

After that, during the spring, I used these already approved projects to
write applications about other projects, which could build upon my
already approved projects. And this too has now started to bear fruit.

First off was an application to SSF, the Swedish Foundation for
Strategic Research. They have awarded me and a researcher from
Karolinska Institutet in Stockholm (Roland Nilsson) a grant of 7.5 MSEK
in total, out of which I will receive 3.5 MSEK (~350 000 USD). The topic
of this project is to use my modelling to extract quantitative fluxes
for all of the metabolic reactions in a cell; this is possible because
of Roland’s unique experimental skills, where he tags metabolites
outside of the cell with C13 carbon molecules, and then uses mass
spectrometry to measure where these tagged carbon molecules ends up in
all in metabolites inside the cell. We will use these money to both
transform this tool from a big potential to something that is useful in
practice, and then also to apply the technique to understanding both
metabolic diseases and cancer on a new level – useful for both research,
drug development, and diagnosis.

The last major grant we got,
and just a few days ago, this Thursday, was from VR, the Swedish
Research Council. This high-prestige grant builds upon my previous
collaboration with AstraZeneca, and will allow us to spend 4.2 MSEK (420
000 USD) to further strengthen our collaboration with AstraZeneca. More
specifically, we will make use of the new and more complete models
developed within the PRECISE4Q EU network (mentioned above) to
understand how a brand new diabetes drug, dapagliflozin, works, and if,
how, and when it can be used to also treat cardiovascular diseases like
stroke, heart attack, and heart failure. This project will also allow us
to understand more about which patients that should have which
treatments, and more about the different mechanisms at play in the newly
sub-divided grouping of diabetes into 5 sub-types.

One very good
aspect of this new situation is that we are really well-prepared for it.
This is due, in part, to some very useful grants we have gotten from the Swedish Foundation
for Research without Animal Experiments. Using this money, we have been
able to train talented undergraduate students in real research projects,
which they have done in parallel to their M.Sc. studies, by awarding
them scholarships (several of the recent blog posts have been devoted to presenting new such students). These new, and previous old, such quite unique students are now ready and eager
to start as Ph.D. students, and they are much more well-trained than
normal applicants would be, which we could find in normal open
announcements. For this reason, we already now know that we will be able to
fill all of the new positions with really great people, and are therefore
looking much forward to working with for, at least, the next 4-5 years. However, all of the new positions will be announced in open competition, so if you are a great candidate, who wants to join our group, don’t hesitate to apply, or to contact me for discussions on joint collaborations or positions.

All in all, it is also a very great feeling to suddenly have such
much money now at our disposal. And also quite humbling. Now we need to
really demonstrate to our funders that we can convert these great money into the equally great
research we have described in our visionary applications. Into research
that will be useful for both other researchers and for those who want to
develop and use new and improved treatments – both treatments such as drugs, and
treatments such as yoga and meditation. It will be great fun to enter this
next step in our group’s development!

This
is a picture of our group during a recent group meeting. Not all were
there, but most of them were. Some of the people in the picture are
excellent M.Sc. students in the end of their studies, who we now can
offer 2 Ph.D. positions. Apart from that, we will
hire two new people, one new Ph.D. student, and one postdoc, but also those will probably be recruits building on previous collaborations and projects. To help as manage all of these new people, we are also very fortunate that Gunnar’s second-in-command in the group, Associate Professor Elin Nyman, now is due to come back after an almost 2.5 year long leave in Harvard,
Portland, and an almost 1 year maternity leave. For all of these
reasons, made possible thanks to the new money described in the post
above, our group will now take a step up to functioning on a new level –
one with more senior people, more people financed fully by the group itself, and with
long-term funding secured. Now we will be able to fully focus on all of
the great research projects we are working on, without worrying if the money will ebb out in the middle of the project!



New student – Kajsa

News Posted on Tue, September 11, 2018 11:28:30

Hi!

My name is Kajsa and I just finished my bachelor at the engineering biology
program. This autumn, and maybe the spring, I’m joining the research preparatory
course. I´m also teaching in a beginners programming course at campus Valla, so
I will spend some time there as well. In my spare time I like to stay active,
which includes everything from movie nights to climbing Sweden’s highest
mountain Kebnekaise.

Here in the
ISB group I will get the chance to continue with the project I was involved in during
the bachelor. In the bachelor project we created a new liver model describing
fatty acid conversion. Now, I will continue the work of the previous students
Valentin Kindesjö, Thirza Poot and Johanna Fridberger to put together a model
that describes fatty acid and glucose fluxes during the day and how it’s
affected by different factors such as insulin and cortisol. My main focus will
be at the fatty acid part and I will continue to work on my liver model as well
as Valentin’s adipose- and cortisol module, which all will be parts of the
bigger model.

I will also
look at newly published data on body fat distribution in connection to diseases
such as type 2 diabetes and coronary heart disease. A future goal is to connect
the data to our models and being able to describe how the fatty acid
homeostasis is affected by stress factors such as disturbed cortisol levels and
why this in some cases cause diseases. By doing this, we are getting closer to
simulating clinical studies and predicting diseases.



New Student- Jonna

News Posted on Thu, September 06, 2018 11:56:14

Hello,

My name is Jonna and I am a Dutch student doing my
internship at the ISB group. I will be staying in Sweden to work on this
project for 3 months. Back home I am a master student in the Medical
Engineering program of Eindhoven Universtity of Technology. This externship is
the final part of my master studies.

Previously I have done most of my projects on
bioinformatics/data analysis so I am very excited to learn more about the
systems biology modeling techniques. This project is a great opportunity to
gain more modeling experience. During my
time here I will be working on modeling the liver.

In my free time I like to swim and explore the city/area a
bit since I am new in town. I’ve spent many of my holidays in Scandinavia (mostly
Sweden) so I am very happy to be living here for a few months. I have had a
part-time job in a swimming pool where I received my first aid certificate,
which I used my first morning in Linköping during helping a patient in the
street after a traffic accident in the city center. So my time in Sweden
started out quit hectic, hopefully that is not a precursor to how the coming
months will be.

I am looking forward to meeting all group members and working
on the project within the ISB group.



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