Tallinn University of Technology
Description of the Organization
Tallinn University of Technology is the only technological university in Estonia and the flagship of Estonian engineering and technical education. The Institute of Cybernetics is a research and development institution at the Tallinn University of Technology, hosting two national centers of excellence in research (Centre for Nonlinear Studies and Estonian Centre of Excellence in Computer Science). As a part of its research, Institute of Cybernetics studies complex interactions and the ways to control artificial, environmental, and biological systems. Relevant to ITFoM, research in Laboratory of System Biology is focused on regulation of intracellular processes and understanding functional influences of intracellular interactions. The laboratory was founded in 2007 with the support from Wellcome Trust (UK). In the research, a mixture of experimental and theoretical approaches are used. As a part of the research, we develop new mathematical models, experimental techniques, and required software platforms to facilitate our work.
As a part of Wellcome Trust funded research, we study structural and functional aspects of compartmentation of adenine nucleotides in heart muscle cells. For that, we use adult cardiomyocytes from rat and trout to take an advantage of structural differences and relate them to intracellular compartmentation. From experimental techniques, we use a range of methods that allow us to study the heart on cell population, single cell, and single molecule levels. We have derived mathematical models to analyze intracellular compartmentation in an intact cell, energy transfer within the heart, and performed molecular dynamics simulations to study interaction between proteins in mitochondrial inner membrane and inter-membrane space. In addition, we have been active in developing mathematical models that link mechanical work performed by the heart to energy consumption of the tissue. It is our vision that such combination of studies on different levels, comparative physiology, and theoretical methods would help in the development of patient-specific approaches in human health care.
As a part of our studies, we have developed several open-source programs that are distributed within iocbio project . Those include programs to deconvolve microscopy images and estimate sarcomere length in real time. Additionally, we developed software to perform symbolic flux analysis that is applicable to genome-scale metabolic networks.
Profile of staff members
Dr. Marko Vendelin is a Wellcome Trust International Senior Research Fellow and a head of Laboratory of Systems Biology in the Institute of Cybernetics. He has been involved in theoretical and experimental studies of the heart with the focus on intracellular compartmentation, energy transfer, and mechanics. Dr. Rikke Birkedal provides an expertise in experimental approaches including application of comparative physiology techniques. Expertise in the area of software development is based Dr. Pearu Peterson, who is one of the principal authors of SciPy, an open-source software for mathematics, science, and engineering [ E. Jones, T. Oliphant, P. Peterson and others, http://scipy.org ].
Five recent publications relevant to the project
1. Illaste A, Laasmaa M, Peterson P, Vendelin M. Analysis of Molecular Movement Reveals Latticelike Obstructions to Diffusion in Heart Muscle Cells. Biophysical Journal. 2012; 102:739–748.
2. Karo J, Peterson P, Vendelin M. Molecular Dynamics Simulations of Creatine Kinase and Adenine Nucleotide Translocase in Mitochondrial Membrane Patch. Journal of Biological Chemistry. 2012; 287:7467–7476.
3. Schryer DW, Vendelin M, Peterson P. Symbolic flux analysis for genome-scale metabolic networks. BMC Systems Biology. 2011; 5:81.
4. Vendelin M, Hoerter JA, Mateo P, Soboll S, Gillet B, Mazet J-L. Modulation of Energy Transfer Pathways between Mitochondria and Myofibrils by Changes in Performance of Perfused Heart. Journal of Biological Chemistry. 2010; 285:37240 –37250.
5. Sepp M, Vendelin M, Vija H, Birkedal R. ADP Compartmentation Analysis Reveals Coupling between Pyruvate Kinase and ATPases in Heart Muscle. Biophysical Journal. 2010; 98:2785–2793.