Simulating cardiac electrophysiological function is one of the most striking examples of a successful integrative multi-scale modeling approach applied to a living system directly relevant to human disease.

Modelling Science Technology and Innovation: Challenges and Opportunities

Katy Börner

CNS, ILS, SOIC and IUNI

Indiana University, Bloomington, IN, USA

The complex network structure of elastin and collagen extracellular matrix (ECM) forms the primary load-bearing component in the arterial wall. Pathogenesis of many cardiovascular diseases has been associated with loss of organization and function of the ECM. However the interactions of collagen and elastin and the effect of ECM structural changes on vascular function are not well understood. This talk will focus on our recent study on the interactions among ECM constituents and how they contribute to the mechanical function of the arterial wall.

Our long-term goal is to develop coherent experimental protocols and mathematical models for understanding the biomechanical interaction between myeloma-initiating cells (MICs, also known as myeloma stem cells) and bone marrow stromal cells (BMSCs, also known as bone marrow derived mesenchymal stem cells) regulating the MIC evolution We have recently shown that 1) BMSCs from myeloma patients (myeloma BMSCs) have higher stiffness and contractibility than normal BMSCs, 2) MICs form more colonies, adhere more tightly and become more resistant to drugs when they are co-cultured with myeloma BMS

Abstract: Dissemination of complex biological models is difficult. Just as experimentalists face challenges with the reproducibility of experimental results due to varying reagents, equipment, and technique, modelers often deal with issues such as ill specified parameters, cryptic code, bugs, and disorganized model versions. XML frameworks such as SBML and CellML have attempted to overcome these challenges by standardizing model specifications. However, this approach still suffersr from reproducibility issues.

There is a critical need to understand how tissue culture stimulation affects tissue construct development and function, with the ultimate goal of eliminating resource-intensive trial-and-error screening. Our goal is to develop predictive assessments of the in vivo performance of biomaterials so that a more rational approach based on a bottom-up modeling toolkit is used to guide the preparation of the required biomaterials. This new predictive approach would save time, animals, costs and accelerate the translation of such repair and regenerative systems.

Model exchange and re-use has been greatly enhanced over the last decade by the emergence of standard model exchange languages such as SBML and CellML. Model design and re-use becomes even more tractable with modularity: larger, more complex models can be built using well-understood smaller models. CellML has long been modular, and SBML now has a modularity 'package' which allows modular model construction. We will present an overview of the capabilities of the modeling standards and tools that facilitate modular modeling.