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

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!



May 11-12, Workshop on biological modelling at LiU

Events Posted on Mon, May 08, 2017 18:21:50

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.



Ph.D. defense of Mikael Forsgren, May 23

Events Posted on Mon, May 08, 2017 13:32:25


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!



Corren-article and debates with colleagues

3R and animal experiments Posted on Tue, February 14, 2017 13:22:11

Late last year, we were featued in a news article in the local news paper: Östgöta correspondenten (often referred to simply as “Corren”). The news article can be seen in the picture below, and it deals with research developed to replace animal experiments, and argues that Linköping university probably is the leading university on this topic in Sweden: we e.g. have a clear 3R-policy, have strong researchers in the area, and both of the two most prestigeous prizes from the Stockholm-based “Swedish Fund for Research without Animal Testing” called “Nytänkaren” has gone to researchers who (at the time) were located in Linköping. The article then goes on to feature an interview with me, and on our type of research: how mathematical modelling can and is replacing animal experiments.

This is not the first time we are featured in media lately. In fact, there have probably been written some 10 news articles in different media on this aspect of our research following our award in late 2015, and they have all been very similar. Most often, the reactions have been very positive, and congratulory, showing appreciation and a new hope over these new possibilities. Similarly, many researchers who have heard my lectures have also been very enthusiastic, and a common reaction nowadays is something like “I had no idea about these recent breakthroughs; I now feel that I lag much behind in my methodology, since I don’t use modelling; what can I do about that?”. This time, however, was the first time these things were featured in Corren, and perhaps for this reason, many of my colleagues read it, and some of them (mostly researchers who themselves do a lot of animal testing) reacted negatively to what it says. I don’t know all that was said about it, but some of the reactions I heard indirectly said that “one shouldn’t write that replacements of animal experiments are possible, since this will lead to the public mandating that this happens generally”. One colleague wrote an email to me directly, stating some specific and somewhat similar concerns about the artice. To this colleague, I wrote a detailed reply, which then led to us writing some rather long exchanges back and forth. All in all, this has now resulted in about 20 pages of text back and forth, dealing with different aspects on this topic.

Since much of these concerns are concerns and thoughts that I have heard many times before, and which most often are based on mis-understandings of what (sound) modelling is about, or in an unawareness of what the most recent developments actually entail, our exchanges have resulted in a growing resolve on my side to do something about this unawareness. To give a little bit of perspective on that: in all previous appearances we have made in the public world, the initiative has always come from some other source; we got the initial award “Nytänkaren” without even applying for it, and in all following media appearances, we have just responded to invitations, to give presentations, to do interviews, etc. Now, however, because of these exchanges, I have realized that I do feel quite strongly about these things, and that I really am concerned about all the mis-conceptions that are floating around (perhaps especially in the biological research communities) concerning what modelling can and cannot do, not only but also in relationship to animal experiments, I am hereby opening a new category in our blog, called “3R and animal experiments”. In this category, I will feature my thoughts and news concerning this exciting topic, and it is intended for both colleagues and for the interested public. Then all exchanges will be public for all to see immediately.

In general, I also want to state that I think that these kind of debates is exactly what I think that science should be about: on topic, honest, and sincere discussions, where ideas can be compared, exchanged, improved, refined, and viewed for all to see.

To start this off, I am attaching the 20 pages of emails below (also including a powerpoint presentation with some figures). That text, however, is pretty long-winding, and in Swedish. Therefore, many of these points will be summarized and explained more simply/clearly in shorter following blog-posts and youtube-videos, which also most often (but not always) will be in English. So stay tuned for that!

Part 1, text from colleagues in italics

Part 2, my colleague’s response to my reply in italics (written then, as a continuous text, without specific replies to my points), upon which I replied in the same way as the first time, by breaking down the statements in small bits, and answering to them one-by-one.

Part 3, final part of the interchange (so far), same structure as above.

Part 4, powerpoint with the figures alluded to in the initial answer (Part 1, above).



Lecture at Linköping vego

3R and animal experiments Posted on Tue, February 14, 2017 12:11:17

A couple of days ago, Gunnar Cedersund held a presentation at the local event “Linköping vego”, which is a little festival on vegetarian-related topics, featuring around 300-500 attendees, 10-15 lecturers, and 10-15 exhibitioners. Gunnar’s lecture was in the “Blanche Lindgren” seminar series, which featured 4×40 min lectures on topics related to research without animal testing. The 4 lectures complemented each other: the first, by Karin Gabrielson Morton, featured an overview of the field as a whole, some historical examples of breakthroughs, and also an overview of the organizing body, the Swedish Fund for Research without Animal Experiments; the second presentation was the one by Gunnar (picture below), who talked about how we and others use mathematical models to reduce and replace animal testing; the third presentation was held by Anna Herland, who is the newest recipient of the same prize that we got the first edition of, “Nytänkaren”, and she works with organ-on-a-chip developments for the human brain; the final lecture was held by Kathrin Zeller who is a member of one of the flag-ship groups for the research fund, which involves an animal-free test for whether a new skin product is likely to lead to allergic reactions. Apart from spanning 4 interesting directions of biomedical research, there were also natural overlaps of interests between us: Anna’s organ-on-a-chip might allow us to test some of our hypotheses regarding how the brain’s fMRI signal is created on a cellular basis, and Kathrin’s omics-based tests for the immune system might complement our own exciting plans and projects on the same topic together with AstraZeneca.

Picture of me in the perhaps most central slide in the whole presentation. The slide illustrates with a simple thought example that a model does not have to be perfect to provide a valid replacement of test animals – it just has to be comparably good/bad as the corresponding animal test. Then, because computer simulations are so much faster and cheaper (among other things) than animal testing, the switch will happen automatically, especially in the industrial sector, which typically switches immediately, if there is money to save. There are already examples where this has happened.

At the event, we also made some initial plans for how to feature ourselves at this year’s edition of Almedalen, to which we this year might go jointly as a group. More on that to come! 🙂



Keynote lecture at Swetox workshop on 3R

Events Posted on Tue, October 11, 2016 07:29:35

The travel period is now just completed, and I am looking forward to writing a report and summary of some of the most important discoveries and news discovered at these meetings in a later blog. Our field – modelling of biological systems – is in a very intensive phase of expansion right now, with a wide variety of events and simultaneous developments going on. Apart from the 4 meetings I/we have attended in the last 3-4 weeks, there are several other important events that we will miss, that are happening now (FOSBE, Magdeburg, Oct 9-12, on Foundations of Systems biology in Engineering) and within the next few weeks (e.g. the first conf of the European Association of Systems Medicine, Berlin, Oct 26-28, Berlin, link).

Figure 1: Me giving a lecture, before recieving the award Nytänkaren from the Swedish Fund for Research without Animal Experiments.

For now, however, I just want to say that one of the developments that is especially interesting to me right now is that concerning modelling in drug and device certifications, and how modelling there can be used in a 3R context, i.e. to replace, reduce and refine usage of animal experiments. I have previously won the first edition of a newly instated prize on this topic – Nytänkaren, Fig 1 – and several of the workshops and conferences I have just attended have had important news on the topic. For instance, I learned that the Food and Drug Administration in the US just have finalized a new report on how to use modelling in device certifications (Fig 2). I also learned interesting details of a second report, due to be published in 2017, which together with the first report will consitute a first complete guide to how modelling should be used in biomedical device certifications. In practice, the same guide will be used as a proxy also for certifications of new drugs, since the principles behind a sound usage of modelling are quite general. In fact, these guides have drawn quite a lot from similar guides already developed and established by NASA, where simulations already are considered mainstream in the development and certification of new space products. In short, I am quite impressed by these guidelines, and think that they have identified more sound principles than are being used in much of today’s research. In other words, these are really important developments!Figure 2: The new report just issued by FDA. Note the date, it was published a few weeks ago!

As a follow-up to these developments, and to me recieving the 3R award Nytänkaren, I have been invited to give a keynote lecture at a workshop at Karolinska Institutet, which takes place today. This workshop is arranged by Swetox and has the overall title “Replace animal use and increase scientific impact”. My talk is entitled “When laying the puzzle instead of just generating new pieces, animal experiments become increasingly irrelevant”. In this talk, I will give a more detailed report on some of the developments above, of my own research on the topic, and about some of the most important showcases that already are existing in the field. If you cannot attend the meeting yourself, you can still check out much of the material: some slides on the FDA developments are available here and a recent overview of our own research including an already FDA-approved glucose simulation model is found here. Finally, a two-sentence summary of the main statement given in the title of my talk is as follows: “if you want to test hypotheses regarding human mechanisms on the systems level, and create a systems-level understanding for the human system, you need data from a single system: humans. Thus, when science switches its focus to this more important endeavor, instead of just generating new hypotheses and pieces of knowledge that never are forged together and tested in a systems-level context, then animal experiments will become increasingly irrelevant”.

Figure 3: First page of my keynote presentation today. It is one of the first times, perhaps even the first time, that I am giving a lecture denoted as keynote, so I am looking much forward to it!



Where to find us in the next 4 weeks

News Posted on Mon, September 12, 2016 21:34:45

I have just jumped on the train from Linköping, Sweden, heading south, and this train ride marks the beginning of an intensive 4 week travelling period, entailing 4 conferences, 6 conference presentations, and numerous visits to groups all across Europe. If you want to catch and meet us along the way, read on below!

Figure 1: Just as in an earlier blog post, I am writing this blog post on the train. This time, I have an interrail ticket and some of my favorite cheeses in front of me!

My first journey heads down to London, where I will attend a workshop on September 14-15 I just very recently discovered: “Accelerating the acceptance of mathematical models as evidence in safety and efficacy decision making”. Apart from some individual exception, this will be a mostly new society of scientists I haven’t interacted with before, but the topic is one that lies close to my heart: how to incorporate mathematical models in drug development and certification. As some of you may know already, we work closely together with AstraZeneca, who also finance a position in my group, on exactly this topic. At the meeting, I am looking forward to hearing more about the Padova diabetes simulation engine (which we have used as a basis for our multilevel type 2 diabetes models), and about modelling for cardiac safety assessments. Both of these are examples where modelling as a replacement for test animals has gone a long way, and it will be nice to hear some updates, and to hear what else has happened in this field recently. This will be the only workshop where neither me nor somebody from my group presents with an oral presentation, and the reason for that is that I signed up only a few days ago, when the programme was already set.

Figure 2: This a picture from the event that in many ways can be seen as the inaugural event of my group: ICSB in Stanford 2009. Since then we have gone to almost all of the ICSB conferences.

My second journey continues on south, down to Barcelona and the International Conference of Systems Biology (ICSB), which is held September 16-20. ICSB (link) is the biggest annual conference in the field, and since it is the first time in a few years that the conference is held in Europe, it is important for us attend. The conference is arranged by the International Society for Systems Biology, headed by Hiroaki Kitano, who also was a guest professor in my group for a few years. We will go there quite a few of us from our group – me, William Lövfors, Elin Nyman, Sebastian Sten, Karin Lundengård, and Johanna Fridberger – and then there are anyway 3 people who intended to go but ended up not going (Maria Engström, Hao Li, and Rikard Johansson). At this conference, many people will be familiar faces, and we are looking forward to meeting both them and new scientists. At this conference we will also give two oral presentations:
1) Karin Lundengård with the presentation: “A mechanistic model for investigating the biological mechanisms behind fMRI“. This is based on our published model for describing the BOLD response in fMRI, and also goes into how it can be used to more correctly and precisely estimate neural activity. The presentation is held 12.15-12.35 on the Monday, in Hall 5.
2) William Lövfors with the presentation: “A phosphoproteome-wide mechanistic model of insulin signaling“. This is the updated version of the story already described in a previous blogpost, and it is held on Sunday 17.35-17.55 in the Auditorium.

Figure 3: The loggo of the Virtual Physiological Human conference.

The third conference is the Virtual Physiological Human (VPH) conference, held in Amsterdam September 26-28. This is a bi-annual conference devoted to multilevel modelling of biomedical, and often even biomechanical, systems. The VPH community is headed by the new director Adriano Henney, who also leads the Avicenna Alliance and is/was the Speaker of the german systems biology network “The Virtual Liver Network”. Before that, the VPH grew out of successful lobbying on the EU level to create a European version of the Physiome project, which e.g. pioneers the multilevel biomechanical and bioelectrical models for the heart. We will go to this conference for the second time, and our troup this time includes me, Rikard Johansson, Tilda Herrgårdh, Hao Li, and Tim Beishuizen. Originally, Elin Nyman also intended to go, but she will already have left for Boston by then. For this reason I will take her oral presentation, and thus give two lectures, along with a third presentation given by Rikard Johansson:
3) Markus Karlsson/Gunnar Cedersund “Meta-modelling combined with non-linear mixed-effects modeling for fast and robust estimation of biomarkers for diffuse liver disease”, Monday September 26, 14.20-14.40 in Emmazaal
4) Rikard Johansson “Model predictive glucose control in intensive care:
assessment in realistic clinical conditions”
, Monday September 26, 15.40-16.00 in Emmazaal
5) Elin Nyman/Gunnar Cedersund, “The Virtual Adipocyte – from Big Data to
simulations of human disease”, Wednesday September 28, 09.40-10.00 in Emmazaal

Figure 4: My first slide, which I added just before holding my presentation at the last edition of ISGSB, in Durham, UK, 2014. Then I had noticed that the ISGSB has something that I really like: lots of social events, and informal activities, and a very relaxed and open athmosphere that really makes people get to know each other. The man down to the right is Stefan Schuster, who is the main arranger of this year’s edition. However, even though he was a part of the competition last year, I am not sure he has picked up on the idea for this year’s event. Nevertheless, an informal music session is on the programme, and they do have a grand piano there, which I plan to make use of!

The fourth and final conference planned to be a part of this conference is the International Study Group for Systems Biology (ISGSB), in Jena, October 4-7. There I (Gunnar) am an intricate part of the arrangements, since I am part of the ISGSB board, and since many decisions are taken jointly by this board. We are going also to this event (link) for the second time, and we will be a troup of 3 people: me, William Lövfors, and Sebastian Sten. Here Sebastian will give our final lecture for this tour:
6) Sebastian Sten, “Investigating hypotheses describing the negative brain responses in fMRI using a systems biology approach”, Friday October 7, 10.25-10.50.

Finally, and perhaps most importantly, I, Gunnar, will travel between all of these conferences by train, and will stay in Europe this entire period. In other words, I plan to visit quite a few research groups, and discuss projects and possibly also give some more lectures in local seminar series. If you are interested in meeting up with me either at one of the above events, or in between some of them, send me an email at gunnar.cedersund@liu.se . I will probably mostly be in France, England, and the Netherlands between September 20-28, and then in Germany and Austria between September 29 and October 7. But even that may be flexible to some degree!

I am looking much forward to this new travelling period, and I am looking forward to meeting many of you – colleagues and friends – at various places along the way!

Spara



New presentation: doing biology without modelling is like driving without a safety belt

Events Posted on Fri, August 26, 2016 20:14:54

So, now
vacation time is over here in Sweden – and work is back with its full
hustle-bustle frenzy. I (Gunnar) started working on Wednesday last week, and
since then I have already submitted one application (to SSF’s industrial Ph.D. programme together with AstraZeneca,
on the creation of a new systems pharmacology platform, based on modelling which is used to
bridge between pre-clinical organs-on-a-chip data and human/clinical
studies), had two supervision days, changed office (my main office is now at
the Department of Biomedical Engineering, and not Clinical and Experimental
Medicine), did the final preparations for the half ironman race this weekend, and went to
Gothenburg to give a lecture in the group of Patrik Rorsman and Charlotta
Olofsson
. It is about this last topic, my presentation, that I want to say a
few extra words also here.

Figure 1: Front page of my presentation earlier today.

The title
of my presentation was “Doing biology without modelling is like driving without
a safety belt – it might work, but it might also go really, really wrong
”. The
talk was a salespitch to an essentially all experimentalist-audience, and it is
based on an image that came to my mind just a few days ago. The image is a response
to some of the most common forms of critique I usually hear against the usage
of modelling: “I could have said that without using the model”, “I don’t believe
that a model can do everything, I think there is still too much that we don’t
understand”, and “the model only seems to provide an extra degree of confidence
on a conclusion I would have said anyway”.

And, the
thing is that I actually – to a large extent – agree with all of those
statements. Modelling cannot do everything, and should not be oversold – but it can do some things, and those things should be properly appreciated. Similarly, many modelling results are conclusions one could have drawn without
the usage of modelling, and what the modelling does is therefore in many respects primarily
to put and extra degree of confidence on that conclusions, if that was the conclusion you anyway would have made. And just like for a safety
belt, when driving: often you don’t need it, you would be fine anyway, but it
is more secure to have it there, to bring an extra degree of security and
confidence to the current situation. In other words, if a model agrees with
your conclusion, you can be more sure that you are correct. However, in the
presentation, I also gave several examples of cases where the modelling
provides a conclusion that seems perfectly reasonable once you see it, but
where the prevailing conclusion before the model-analysis was done, actually
was a very different one. Apart from our main diabetes examples, I pointed to three probably less known such stories:

Figure 2: The difference between the new way of calculating EC50 values (black) with the old one (red).

1) Our EC50
story
, published in FEBS J last year. There we showed that a simple model-analysis could detect a problem with
a previous way of calculating EC50 values: that the steady-state was not
reached in-between the changes in stimuli. In other words, the resulting curve was not an increase in steady-state values, but a long transient overlaying of overshoot responses. That
new interpretation of the data had some predictions, which we verified in independent
experiments, supporting our new interpretation of the data. Furthermore, it was
experimentally not possible to modify the protocol, to wait as long as one should to reach steady-state. Therefore,
the only way for this system to get correct EC50 values (corresponding to steady-state values) is to do what we
propose: to fit the model to a transient responses like the one already existing, and
then use the model to simulate the experiment as it ideally should have been done to start with.
As you see in Figure 2 above, the new, more correct EC50 value is almost completely non-overlapping with the old one.

2) An
earlier story of muscle metabolism, where we showed that a seeming
contradiction and missing link – which had been investigated for 25 years – in fact
was not a contradiction at all, but merely a mis-interpretation of data. And
that re-interpreted version sounds very reasonable once you see it. In other
words, for 25 years, people had believed that a not yet discovered regulator of
glycolysis was active in anaerobic muscle recovery, but our modelling showed
that no search for such an unknown regulator is necessary: a correct analysis
of the data shows that the conventional regulators are sufficient to explain
the observations.
This story is not yet published, but anyway available as
chapter 11 in my Ph.D. thesis.

3) Another
recent story on interpretation of data for the IL1beta analog Anakinra (Palmér et al, CPT Pharmacometrics Syst Pharm, 2014). In this
story, we had a look at data that seemed to be too good to be true, and
therefore were disbelieved by many: that Anakinra could have lasting positive
effects on the diabetes readout HbA1c as long tie as 1 year after the start of
the treatment, even though the treatment itself only lasted for 3 months
. We
showed that a simple model based on pre-clinical data alone did actually
produce that clinical output as well. In other words, we showed that the
initial response was that the initial disbelief in the clinical data was unnecessary: they were perfectly aligned with the pre-clinical data.

Figure 3: Last page in the presentation, summing up the main advantages of doing modelling, i.e. pointing out some of the drawbacks of not using it.

These are three examples that show that
modelling in principle does not do anything that one anyway does: analysis
of experimental data to draw conclusions and suggest new experiments. However, modelling does these things in a more reliable fashion, and it is easy to go wrong otherwise. In other words, to do biological data
analysis without modelling, is just like to driving without a safety belt: it
might work, but it might also go really really bad – throwing away 25 years
of your life.

Figure 4: On the train on the way back, I happened to be seated right next to a very nice systems biology colleague of mine: Adil Mardinoglu. He told me that he and some colleagues of him had read my last blog post, and wanted to contact me about it. So that is actually the reason why I got inspired to write a new one as well!



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