The ISBGroup Blog

Education-wise, we in ISBgroup have one major highlight during the year: our course TSRT17, the systems biology project course.

This course runs for third years students at TB (engineering biology), and this year we are also glad to have with us students from the I-Bio programme (biology with a more engineering and management training), and also some additional undergraduate and Ph.D. students who only take the initial part of the course for general training.

The initial part of the course consists of 5x2h lectures, 2 exercises, and a 12h computer lab. This gives them a crash course in systems biology, where they learn to put their various pieces of knowledge together into the art of model-construction and analysis.

The second part of the course is the major part of the course. Then they are divided in groups of 6-7 students, and given a scientific questions. This question is a real unanswered but interesting biological question, and is different for each group. The different projects all have the same character, however, since they are all structured around the analysis of a given set of data, where the task is to analyse this data for possible mechanistic explanations to the cause of the observations, and usually centered around two or more competing and plausible mechanistic hypotheses. The task is therefore to see which of these hypotheses that can be rejected, and to identify interesting and well-characterized core-predictions, which allows future experiments to test the conclusions, or differentiate between previously non-differentiable explanations, etc. All-in-all, the students are really doing real scientific research problems, which is really cool actually, both for us and for them.

The course will last for the entire semester, and there is a big presentation day on May 18, which is open for all, and which includes both a poster session, presentations by the students and by other invited lecturers, and by a prize-ceremony for the group with the best name and logga…! 🙂

So, welcome on May 18, to come and see the results of this years TSRT17-edition.

Now both contracts are signed, and all is finished – Hiroaki Kitano and Jens Timmer will be guest professors in our department during the next 2 years!

Hiroaki Kitano is one of the founders of systems biology, by e.g. having written some of the early hallmark reviews/commentaries in Nature and Science establishing the concept, and by arranging the first edition of the the biggest conference in the field: International Conference on Systems Biology (ICSB). Kitano is also chairman of the International Society for Systems Biology, which for instance oversees the ICSB, and we will try to make use of this fact to bring this conference to Linköping, perhaps even as early as 2013 or 2014. We have also already applied for additional Japan-Sweden funding, to – apart from the money coming with the professorship – further improve our possibilities for joint activities, and exchange of students, personnel, etc. The main topic of interaction will probably be hierarchical modelling, i.e., such models that can be developed in a distributed fashion, where different sub-models are put together in an object-oriented fashion.

Jens Timmer leads one of the biggest groups around in systems biology, with over more than 35 employees and encompassing collaborations with many different and leading biological groups. Jens has also been the Speaker for HepatoSys, the biggest national network around in Systems Biology. The most important reason why I am very thrilled about this collaboration, however, is that Jens’ group is doing their modelling and model-based analysis in a fashion that is very similar to ours. They also take a data-analysis point-of-view, where the intent is to extract as much information as possible from the data, e.g., by considering also the quantitative aspects of the data features. Similarly, they are also keenly aware of many of the most important pitfalls in such an analysis – such as neglection of the over-parametrization issue, or blind usage of analytical formulas for the statistical tests. We are also already collaborating on the development of improved methods to handle this issues (for instance through my previous additional affiliation as Senior External Fellow in Freiburg, and through our shared employement of Rikard Johansson), such as bootstraping-based statistical tests, and profile-likelihood-based confidence interval calculations.

These recruitments are the result of our headmaster (rektor) having an initiative of attracting some really high-profile people to our university, and of me having been a post-doc in both these groups, and therefore knows them personally. In short, we are very thrilled about this development, and will now start to think about various ways in exploiting this new fact as much as we can: when marketing our systems biology centre here in Linköping internationally and locally, when planning for future recruitments and exchanges of staffs and students, when designing new research projects, etc. All of these aspects now suddenly have drastically improved potential!

The results from this year’s evaluation and financing round from the Swedish Research Council (VR for Vetenskapsrådet) has now arrived (nov 2010), and it turned out that both me and Peter came out on a very good side of things.

* Peter Strålfors got an increase from already high 900 000 SEK/year to 1 000 000/year, during the next 3 years

* I got a research fellowship position (Forskarassistent) which means salary for me and additional money, in total approx 5.5 MSEK during the next 4 years.

There are several reasons why this is very good news. First, VR has the only really ambitious evaluation process in Sweden, where they really evaluate you by the science. This means that this is the best such quality stamp that you can get on the national level, and we both got almost as high as you can get (our group got ranked as “worldleading”, for instance). For this reason, it means that this increased money we got now will be multiplied by making it even easier to get money from other funding sources in the future: from the university there is an automatic co-funding of approximately the same order of magnitude; many other research agencies simply look at what you got from VR and scale their financing by that; and this outcome means that Peter will stay among the league of prioritized professors at University. Finally, my specific position means that I have a 4 year position ensured, which is a high-status position, and which generally goes beyond the post doc level. Since this is the “magic” step in scientific carreer (e.g., this year only 8% approval) this means that I now have very good chances of implementing my various scientific plans, for instance by keep building up my research group here in Linköping on a long-term basis etc.

So now we just need to figure out how to best celebrate and make use of these new possibilities! 🙂

We have just published a new
paper in JBC!

Mass and information feedbacks through receptor
endocytosis govern insulin signaling as revealed using a parameter-free
modeling framework, Cecilia Brännmark, Robert Palmér, S. Torkel Glad,
Gunnar Cedersund, and Peter Strålfors, J Biol Chem, 2010, doi:
10.1074/jbc.M110.106849

This it the first really
extensive systems biology paper coming out of our lab, and it is the
result of several years of iterations between experiments and
mathematical modelling. It builds on the same directions our previous PLoS
Comp Biol paper, which seeks to characterise the early events of
insulin signalling, i.e. the activation of the insulin receptor, and the
insulin receptor substrate-1 during the first few minutes. This
sub-system is beneficial to study because many relevant hypothesis can
be put forth which only describe this little isolated systems; in other
words, the tested models are small and strong conclusions can be made.

This
is the also the first paper where we really demonstrate our idea of
core predictions. Such predictions are defined as uniquely identified
model properties (based on the model structure and the available
experimental data), even though the individual parameter values might
not be uniquely identifiable. We use an especially developed
optimization algorithm to determine such properties, and then use these
properties to identify relevant new experiments.

The
future plans are to extend this model in several directions. Primarily,
we will be looking more downstream, to include other target proteins and
cellular processes. This inclusion has the ultimate goal to result in a
computable adipocyte and adipose tissue module, which both is
consistent with our detailed understanding of the cellular and local
data, and with the whole-body perspective, relevant for type 2 diabetes
and clinical trials. We will, however, also keep studying these early
processes more; the present results put receptor endocytosis at the
heart of the matter, and we hope to achieve further insights on the role
and relevance of this sub-process for insulin signalling, by combining
advanced single-molecule microscopy with model-based data analysis using
stochastic modelling.

So look forward to that! 🙂

We have just published a new paper, which is now available online here, and the citation details are as follows:

Zooming of states and parameters using a lumping approach including
back-translation, Mikael Sunnaker, Henning Schmidt , Mats Jirstrand and Gunnar Cedersund BMC Systems Biology 2010,
4:28, doi:10.1186/1752-0509-4-28

It is the first of a series of papers coming out from us concerning zooming, i.e., the ability to switch between two versions of the same model – one large and one small – where both models describe the same system, and where there is a mapping between the states and parameters in the two different models.

Such zooming may be useful in many situations. One example is in object-oriented modelling, where differently detailed models can easily be replaced for each other as one switches focus of interest. Another important application is when the reduced model is identifiable, i.e. where all its predictions are uniquely identified from the given data. In this case the zooming allows for the addition of interpretation to the reduced entities (states or parameters), and this is the ultimate step in the creation of a core-box model.

There will be several follow-up papers on this paper. In one of these, we extend the results to a certain type of non-linear systems. In another paper, we concern ourselves with the mapping between two general models, i.e., where the smaller model has not been obtained using model reduction. And in a third paper, we will show how the creation of a zoomable, hierarchical, whole-body model for glucose homeostasis can reveal new insights and improvements regarding our cellular experimental system for studying insulin resistance and type 2 diabetes.

So look forward to this!

This year will be an important year for our group, when many things will mature in various ways.

This will be the year when we will have to transform some of the student affiliations into scholarship students, and some of the scholarship students into Ph.D. student affiliations, and in this make use of our various sources of internal and external funding, and make use of all our collaborations with other groups. An example of the latter is our important collaboration with Freiburg, where I (Gunnar) have an external fellowship, and where half of Rikard’s employement is financed.

This will also be a year when we will will transform many of our almost finished projects into publications. Last year we grew substantially in personell, and this has allowed us a quite new work capacity, which we must learn to make use of properly, and make visible in terms of an increased rate of publications. Several papers have also been submitted or re-submitted in the last weeks, and with some luck, this will soon start showing off as new interesting publications, showing some of our ongoing projects more visibly to the rest of the world.

In this early phase of the year, we are also running the second edition of TSRT17, which is our own systems biology course. It is our intention that this year’s edition will be a clear improvement compared to last year, and that we just like last year will be able to recruit some of the most talented students as scholarship or project students.

One example of how this process is continuing is Mikael Forsgren, who took the course last year, has been employed in the group of Peter Lundberg ever since, and is now doing a little project also in our group, where he helps us finalize an interesting project on core-box modeling and back-translation. Two other new people in the group are Lovisa Österlund who is doing a boolean approach to the study of mTOR and autophagy and their relation to insulin signaling, and Gustaf Ullman, who will become our new expert on stochastic and single-molecule modelling and simulations.

We have also continued our team building activities, through regular whole-day meetings where we present our work for each other (see up-coming and previous events), through the continued application of wave and other online communication tools, and through various joint social activities such as weekly game-nights, and a joint vacation weekend in Romme. We also plan to expand our weekly meetings to include seminar-series with internal and external lecturers; this will also be a part of the continued launching and starting up of the Linköping centre for systems biology, which hopefully will also be stimulated by our upcoming recruitment of two world-leading systems biology guest professors.

All in all, we are moving into a very exciting year, where many of the plans and projects that were started last year hopefully will mature and bear lots of scientific fruits.

Summing up 2009, it must be said that it without a doubt has been the most important and expansive year so far, at least with respect to the systems biology part of the group.

Going into the year, there were only me (Gunnar), Cecilia “Ia” Brännmark, and two new students: Elin Nyman and Rikard Johansson. Then interesting and ambitious students appeared one-by-one, e.g., Robert Palmér, Fredrik Bäcklund during the spring/summer, Eva-Maria Hansson and Oscar Samuelsson during the early autumn, and Amanda Jonsson during the late autumn. This means that the group has more than doubled in size in a short period of time, and we have been in a very nice feeling of growth and “anything is possible” during the entire year. During this time we have spent quite some time to get a nice group feeling, creating our own home page, logga, name, and has also started to improve our internal communications through the adoption of the new and powerful google wave online communication tool. We had also to establish new routines for our internal meetings: we initiated weekly Monday meetings, and changed our joint supervision time where all students were present to entire supervision-days, all because of the rapid growth of the group.

2009 was also the year when TSRT17, our own course was launched. This is a project course that is held for 3rd years students at the Technical Biology program, and it will be held anually from now on. The project was done as a collaboration with the system identification/control engineering group at ISY (led by Torkel Glad and Lennart Ljung), and the MR-group led by Peter Lundberg. This course will be important for us to train and inspire students to be future project, MSc, and Ph.D. students in our group.

Another important event this year was to start the process of forming a systems biology center at Linköping University. We had a first meeting with all 15 groups, and have also combined these networking efforts with the participation in the formation of a national Wallenberg Institute for Systems Biology, and in various European network formations on systems biology of diabetes, several of which have been coordinated by us.

This important year will probably in many ways be remembered as the defining year of our group, and it is with great enthusiasm and anticipation that we move into the new year and into the new decade.

These last few weeks, I (Gunnar) have been almost completely buried under some high-maintainance application writing. Last week there was the deadline for submitting to CENIIT. This was stimulating as it marked the expansion of our group to the technical faculty, which is where I come from scientifically, and where I want to have and am establishing a strong second foot; in particular regarding methods for system identification.

Today, however, there was an even bigger deadline: to the FP7. It was a major network application, involving some 20 partners, 5 pharmaceutical companies, 12 MEuro, etc etc. It turned out very nice in the end, but keeping in contact with that many people is quite exhausting. Scientifically it was based on a continuation of Elin’s pilot study, extending the Dalla Man model to a multi-scale model also incorporating biochemical details.

Otherwise on the news front, Siri Fagerholm defended her mid-Ph.D. report last week (October 21).

When looking forward it is time to fix with the final arrangements so that we can launch the seminar-series associated with the Linköping Centre for Systems Biology, which should start in some 3 weeks or so. It is also time to start preparing in detail for next years edition of the Project course in Systems Biology….!

And it will be reaally nice to at last have time to do some science and supervision again! 🙂

Gunnar