The ISBGroup Blog

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!

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

The ISB group would like to extend a warm thank you to everyone who attended the SystemsBiology@LiU-day. We think that this day was a huge succes as an initial ice-breaker between the various groups at Liu which work with Systems Biology.

We are now working on setting up the mail-list we discussed. If you wish to be a part of the list, please send us a mail

Yet again, thank you, and if you missed the day, make sure to sign up to the mailing list in order to not miss out on any future events.

——————
The ISB group

This is the first entry in our new home page experiment: a group blog!

Right now, there are many things going on, and here is a short summary of some of the most exciting things.

– At Linköping university we are arranging an all day symposium on systems biology on Wednesday Sept 30. It is for and with all scientists working with systems biology at the university, and at the least 15 groups at ~10 different institutions are represented. I think that it is really cool that so many groups are already working with systems biology, and we hope that the day will be a success, leading to for instance the formation of University-wide network, a regular and joint seminar-series/Ph.D. course with internal and external lecturers, and the arrangement of a first edition of Linköping Conference of Systems Biology. More info here.

– Last week I was in Warwick, UK, and gave a lecture

Sound identification and model merging when studying type 2 diabetes on our projects at the MOAN break-out session at the International Conference for Complex Systems. Here is more information.

– A few weeks ago four of us (I, Cecilia Brännmark, Rikard Johansson, and Elin Nyman) went to the International Conference of Systems Biology at Stanford, USA. It was a very inspiring time, and we were happy to note that our group had the biggest Scandinavian representation at the conference, which is cool since this is the biggest conference in the field. We four presented one posters each, and I also had one with prof George Verghese from MIT. Here are links to the posters: 1,2, 3, 4, 5.

– On the way back I stayed a few days in Boston, and worked together with George Verghese on join matters. I also visited some other groups, and gave a guest lecture at Merrimack, which is a very cool company since they have almost completely integrated System Biology in their drug and anti-body development pipeline.

That’s all for now – please check in again later and see how our work and home page is progressing!

Gunnar