- September 13, 15.30-17, Martin Adiels, Gothenburg University, "Whole-body models for fatty acid homeostasis", Hälsans hus, lärosal 1, (map)
September 17, 10.15-12, Jan Hasenauer, University of Stuttgart, Tutorial in the set-identification matlab toolbox, HUB8, (in the HU library).
September 20, 15.30-17, Jan Hasenauer, University of Stuttgart, "Guaranteed predictions in spite of limited knowledge and uncertainties? - A case study for the NF-kB signaling pathway", Glashuset, B-house, Campus VallaAbstract:The main goal of system biology is a quantitative description of cellular processes and the understanding of those. Unfortunately, achieving this aim is rather difficult, as models of biological systems are subject to a significant degree of uncertainty. This uncertainty arise from limited knowledge about the system, mostly due to limitations in the experimental technology, and/or large variations in environmental and internal boundary conditions. The uncertainties become manifest in a only partially known interactome as well as unknown parameter values.
- October 10-15, 2010, International Conference of Systems Biology, Edinborough, UK, (link)
June 3-5, 2010, Systems Biology of Mammalian Cells, Freiburg, Germany (link). Elin Nyman and Gunnar Cedersund will give the oral presentation: "Combined top-down and bottom-up modelling provides internally consistent explanations of whole-body glucose homeostasis through the identification and elimination of data inconsistencies and missing regulations" Rikard Johansson will present the poster "A two-dimensional boostrap method for model discrimination", Gunnar Cedersund will present the poster "Mass and information feedbacks through receptor endocytosis govern insulin signaling as revealed using a parameter-free modeling framework", and Eva-Maria Hansson will present the poster "Towards a mechanistic explanation of the causes of insulin resistance in type 2 diabetes, which incorporates mTOR, autophagy, and mitochondrial dysfunction".
June 26-July 1, 2010, 35th FEBS Conference, Gothenburg, Sweden (link) (special focus on systems biology this year). Gunnar Cedersund and Marcus Krantz will present the short talk: "Mapping cellular signal transduction", in Section B3 - Global networks, June 29 at 13:00.
June 7, 15.30-17 Maria Bartholome Rodriguez, Freiburg University, Germany, "Towards mathematical modelliing of insulin induced signalling in hepatocytes: The point of view of an experimentalist." Conradsalen (HU, main house, A-elevators, floor 11, right in the corridor) (map)
The enormous regenerative capacity of the liver is unique among mammals. Strikingly, during this intensive phase of proliferation, hepatocytes continue to ensure their essential metabolic functions such as glucose regulation, degradation of toxic compounds, and synthesis of proteins. The hormone insulin is an essential factor in all these processes. The complexity and the unique effects of insulin in the liver are the particular concerns in which our group has been involved over the last years. Thus, the peculiarities of the insulin signaling in the liver will be focal point of my talk. I will give you first a short overview of our efforts concerning the detailed recovery of dynamic, spatially resolved and reproducible high quality experimental data on insulin-induced signal transduction in primary murine hepatocytes, involving several experimental techniques. Second, I will concentrate my talk to the experimental steps involved in constructing a mathematical model for the complex dynamics regulating the activation of the insulin receptor - a key molecule for insulin signalling in the liver.
June 8, 10.15-12 Cecilia Brännmark, isbgroup/IKE, will defend her mid-term Ph.D. thesis "An integrative systems biology approach to insulin signaling" Hälsans hus, Lärosal 1, (map) Paper 1, Paper 2. Opponents: Roland Nilsson (KI, Stockholm, Sweden; Harvard, Boston, US), Maria Bartholome Rodriguez (Freiburg Klinikum - Freiburg, Germany)
June 9, 13.15-14 Amanda Jonsson, isbgroup/IKE, will defend her M.Sc. thesis "Modelling frameworks for cellular signalling". Conradsalen (HU, main house, A-elevators, floor 11, right in the corridor) (map)Abstract:
Type II diabetes is one of many diseases that are coupled to dysfunctional information processing on the cellular level. Such cellular information processing is carried out by highly complex protein networks, and this complexity is the main reason why mathematical models are becoming increasingly useful in the area of cell biology and drug discovery. The most widely used modeling framework is ordinary differential equations (ODEs). However, to be able to formulate ODE models, a detailed knowledge of the system is needed. As data are often sparse, and as high confidence prior knowledge is in general missing, alternative modeling frameworks are in many cases advantageous, and can serve as a useful complements to ODEs.
We here present an evaluation of different modeling frameworks, with focus on Boolean Networks and Bayesian Networks. A survey of the properties of the frameworks as well as a re-analysis of models previously built using ODEs is performed. Boolean Networks, which constitute a rough and less detailed modeling framework than ODEs, have been used to create middle-sized networks of the early insulin signaling events involving a few down-stream mediators in the insulin signaling pathway. Bayesian Networks, which are fundamentally different from both ODEs and Boolean Networks, have been thoroughly investigated. An attempt has been made to re-create predictions from a formerly created ODE-model in a Bayesian Network framework. Our experience is that Bayesian Networks may not be able to give as specified predictions as ODEs, but that they are useful in situations where Boolean Networks and ODEs both fail.
In summary, all modeling frameworks have their strengths and weaknesses, and depending on the question, available data, and prior knowledge, different frameworks should be chosen. As a final step, the insights gained through the evaluation of modeling frameworks have been used to create a recommendation on how different types of information can be put together into a meaningful modeloriented database, and how to link this database to the creation of a multi-physics adipose tissue module, in which different modeling frameworks can be combined.
- May 7, 9.30-16, Presentation day with ISB-group (open for all), see www.isbgroup.eu, Hälsans hus, Lärosal 1, map
- 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." Conradsalen (map)
- May 17, 15.30-17, Roland Nilsson, Harvard/Karolinska Institutet, "Discovering regulators of metabolic pathways through large-scale integration of gene expression data" Almen, HU, (map, map2 entrance 65, directly up to the right))
As whole-genome expression profiling has become increasingly affordable, publicly available repositories of microarray data are expanding rapidly. Still, a large fraction of the enormous information content in these databases remains unexplored. In this talk, I will discuss data integration techniques allowing us to take advantage of this data to discover new components of metabolic pathways. Specifically, we have developed a technique that systematically searches data repositories for genes that are consistently and specifically co-expressed with a pathway of interest. Using this method, we have successfully identified five proteins as required for functional heme biosynthesis, and a novel regulator of oxidative phosphorylation acting on mitochondrial mRNA.
- May 19, 14-14.45 Mikael Benson (Gothenburg University, leader of 2 systems biology FP7-networks) will present his research, "Kan nätverksbaserad analys av genomik data användas för att skräddarsy mediciner?" (might be in Swedish), Library of Children's clinic, level 15, Campus-US, Hospital main building
- May 20, 15.15-17, Student presentations from the project course TSRT17, 3x10 min presentations from projects related to systems biology of type 2 diabetes and insulin signalling, and 2x10 minute presentations from projects related to image analysis using MRI to diagnos liver and brain. The last hour contains a poster session. C3, C-house, Campus Valla (map)
Earlier than may 2010
Mika Gustafsson will defend his dissertation
“Gene networks from high-throughput data – Reverse engineering and analysis” two weeks from now. The thesis can be found at DIVA.
Time: Friday 26 March 2010 at 13.15
Place: Kåkenhus, Campus Norrköping, lecture hall K3 (Önnesjösalen)
Opponent: Prof. Reinhard Guthke, Jena
You are all most welcome.
Michael Hörnquist, itn
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.
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)
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
FP7 Lunch SeminarsOn 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 PresentationOn 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.
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 2009On 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.
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 PresentationWednesday, 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-dayOn 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.
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
- Structured Reduction of Dynamic Biochemical Models: A case Study Using Models of Yeast Glycolytic Oscillations
Gunnar Cedersund, George C. Verghese
Senast uppdaterad: 2010-11-27