January 2011

Every Monday 16-17 we have an open group meeting, where all interested students and scientists are welcome to participate. We are located in the coffee room at floor 12, Cellbiologen, Hälsouniversitet, Linköping, and the discussions for the most near-lying Mondays are as follows:

• Jan 17, 2011, First meeting of the year, start-up discussions
• Jan 24, 2011, Overall review of interesting papers in the last 2 months, selection of interesting papers to discuss in the upcoming weeks
• Jan 31, 2011, Discussion of the paper "Kinetic evidence that Glut4 follows different endocytic pathways than the receptors for transferrin and alpha-2-macroglobulin", Habtemichael et al, JBC, 2011

May-June 2010

* May 7, 9.30-16, Presentation day with ISB-group (open for all) schedule

* May 11, 16.30-17.15, Gunnar Cedersund gives a lecture at the Ph.D. course SIMON, "What can you do with your relaxation data. A systems biology approach."

* May 17, 15.30-17, Roland Nilsson, Harvard/Karolinska Institutet, "Discovering regulators of metabolic pathways through large-scale integration of gene expression data" Abstract

* May 19, 14-14.45 Mikael Benson (Gothenburg University, leader of 2 systems biology FP7-networks, and interested in joining us here at LiU) will present his research

* June 7, 15.30-17 Maria Bartholome Rodriguez, Freiburg University, Germany, will present her research related to systems biology and insulin signalling

* June 8, 10.15-12 Cecilia Brannmark, isbgroup/IKE, will defend her mid-term Ph.D. thesis

* June 9, 13.15-14 Amanda Jonsson, isbgroup/IKE, will defend her M.Sc. thesis "Modelling frameworks for cellular signalling"

* May 12, 13.15-14.00, KTH, Stockholm, Sweden, Gunnar Cedersund gives a lecture for S3, "Strong conclusions regarding intra-cellular networks without knowing or uniquely estimating the parameters"

* June 3-5, 2010, Systems Biology of Mammalian Cells, Freiburg, Germany (link)
From our side, Gunnar Cedersund, Rikard Johansson, Elin Nyman, and Eva-Maria Hansson attended

Master Thesis Presentation

On Friday, March 26th, at 13:15 in Conradsalen, HU, Eva-Maria Hansson presents her master thesis work titled "Towards a mechanistic explanation of the causes of insulin resistance in type 2 diabetes - incorporating autophagy, mitochondrial dysfunction and the protein kinase mTOR". Abstract as follows:

Type 2 diabetes is a global disease which affects an increasing number of people every year. At the heart of the disease lies insulin resistance in the target tissues, primarily fat and muscle. The insulin resistance is caused by the failure of a complex signalling network, and several mechanistic hypotheses for this failure have been proposed. Herein, we evaluate a hypothesis that revolves around the protein mTOR (mammalian target of rapamycin) and its feedback signals to the insulin receptor substrate-1 (IRS1). In particular, we have re-examined this hypothesis and relevant biological data using a mathematical modelling approach. More...

ISB Group, Whole Day Meeting 2

On wednesday February 17th, 2010, the ISB group met for yet another day of talks and discussions.
Location: Halsans hus, lokal 1 (morning). Flemming-salen (afternoon)
Schedule

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ISB Group, Whole Day Meeting 1

On January 18th, 2010, the ISB group met for whole day talks and discussions.
Location: HUB8, Health University library group room 8
Time: 10.15-16.30
Schedule

FP7 Lunch Seminars

On Monday, 23rd of November, Professor Peter Strålfors participated in a lunch seminar with EU FP7's program officer for diabetes research. They discussed challenges facing diabetes research. Professor Strålfors argued for 1) the useage of modeling as a tool for handling the biological complexity of insulin action in healthy and diabetic induviduals, as well as for handling large scale data; 2) experimental data obtained from human patients is necessary for a full understanding of this human disease; and 3) modeling aimed at identifying new drug targets for development of of new treatments of diabetes.

Master Thesis Presentation

On Monday, November 16th, Fredrik Bäcklund defended his master thesis work "Model-based evaluation of an insulin signaling feedback hypothesis" at campus Valla and passed with flying colors.

Abstract:
The insulin initiated intracellular signaling network is a highly complex system, with many challenges to its analysis. Here, we focus on i) a set of previously collected experimental time-series yielding curves with complex behaviors, and ii) a previously proposed mechanistic explanation, which includes multiple feedbacks. We have translated this previously only verbal hypothesis to a mathematical model, and made a model-based analysis of the data. This analysis revealed the need for a non-linearity in one of the feedbacks of the model. We also achieved a reasonable fit to the complete data set using the full model although it does not capture some of the more detailed biphasic behaviors. However, to optimize such a complex model is difficult, and this points to the need for new and/or improved modeling approaches. To this end, we have developed a new approach based on the intermediate formulation of a linear model. Apart from achieving the sought after overshoots and biphasic appearances of the data, this effort resulted in a rather general strategy for generating models with specifically tailored time-series appearances. This approach opens the door to a new type of model-based data analysis, but to be truly useful in a systems biology context, important challenges regarding the biological interpretation of the linear model remain.

BioSys 2009

On Friday, October 16th, Gunnar gave a talk at the BioSys 2009 conferance in Hamburg. Yet again, it concerned a topic very close to our hearts: "Identification of core predictions: uniquely identified model properties in unidentifiable models of insulin signalling". Follow the link for more information.

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ISY diagnosis seminar series

On Tuesday, October 13th, Gunnar presented the work in our group with focus on obtaining unique properties of unidentifiable models. It took place at ISY's seminar-series on diagnosis.

When: October 13, 10.15-12
Where: Systemet, ISY, Linköping University, Sweden
What: Unique identification in unidentifiable models, its development for systems biology, and its possible applications to diagnosis
For whom: All that are interested, it is centered around discussions, and very informal

Master Thesis Presentation

Wednesday, October 7th, Peter Nyberg presented his master thesis work "Evaluation of two Methods for Identifiability Testing". A joint supervised project of our group, Division of Automatic Control at the Department of Electrical Engineering, and Mathcore. The presentation took place at campus Valla, Glashuset (Building B, entrance 25) at 10:15. Abstract as follows::

This thesis concerns the identifiability issue; which, if any, parameters can be deduced from the input and output behavior of the model? The two types of identifiability concepts, a priori and practical, will be addressed and explained. Two methods for identifiability testing are evaluated and the result shows that the two methods work well if they are combined. The first method is for a priori identifiability analysis and it can determine the a priori identifiability of a system in polynomial time. The result from the method is probabilistic with a high probability of correct answer. The other method takes the simulation approach to determine whether the model is practically identifiable. Non-identifiable parameters manifest itself as a functional relationship between the parameters and the method uses transformations of the parameter estimates to conclude if the parameters are linked. The two methods are verified on models with known identifiability and then tested on some examples from system biology. Although the output from one of the methods is cumbersome to interpret, the results show that the number of parameters that can be determined in practice (practical identifiability) are far fewer then the ones that can be determined in theory (a priori identifiability). The reason for this is the lack of quality, noise and lack of excitation, of the measurements.

SystemsBiology@LiU-day

On September 30 we arranged the SystemsBiology@LiU-day at Linköping University, Sweden. See this link for more information.

UPDATE: We are in the process of creating a mailing list for Systems Biology at LiU. Please let us know if you want to be in the list.

ICSB

In September we attended the 10th International Conferance on Systems Biology (ICSB) at Stanford University. Amongst others, we presented the following posters:

• Elucidating Mechanisms of Early Insulin Signalling in Primary Adipocytes and Hepatocytes: A Joint Systems Biology Effort
  Rikard Johansson, C. Kreutz, C. Johansson, M. M. Bartolomé Rodríguez, P. Strålfors, J. Timmer and G. Cedersund
• Multi-Level Hierarchical Modelling of Glucose Homeostasis
  Elin Nyman1, Cecilia Johansson, Anita Öst, Jan Brugård, Fredrik Nyström, Peter Strålfors and Gunnar Cedersund
• Analysis of the Early Phase of Insulin Signalling in Adipocytes: An Integrated Experimental-Mathematical Modelling Approach
  Cecilia Brännmark, Gunnar Cedersund, Peter Strålfors
• Identification of Core Predictions – Uniquely Identified Properties of Over-Parametrised Models
  Gunnar Cedersund
• Structured Reduction of Dynamic Biochemical Models: A case Study Using Models of Yeast Glycolytic Oscillations
  Gunnar Cedersund, George C. Verghese