Combining analysis and synthesis in a model of a biological cell

We have previously described a top-down analytical approach, Cell Assembly Kit (CellAK), based on the object-oriented (OO) paradigm and the Unified Modeling Language (UML) and Real-Time Object-Oriented Methodology (ROOM) formalisms, for developing models and simulations of cells and other biological entities. In this approach, models consist of a hierarchy of containers (ex: cytosol), active objects with behavior (ex: enzymes, lipid bilayers, transport proteins), and passive small molecules (ex: glucose, pyruvate). In this paper we describe the Substrate Catalyst Link (SCL) bottom-up synthesis approach [17], the concept of autopoiesis on which it is based, and what we have learned in trying to integrate this approach into CellAK. The enhanced CellAK architecture consists of a network of active objects (polymers), each of which has behavior that causally depends partly on its own fine-grained structure (monomers), where this structure is constantly changing through interaction with other active objects.

[1]  Barry McMullin,et al.  Towards the Implementation of Evolving Autopoietic Artificial Agents , 2001, ECAL.

[2]  Barry McMullin.  Computational Autopoiesis: The Original Algorithm , 1997 .

[3]  Pedro Mendes,et al.  GEPASI: a software package for modelling the dynamics, steady states and control of biochemical and other systems , 1993, Comput. Appl. Biosci..

[4]  Ivar Jacobson,et al.  The unified modeling language reference manual , 2010 .

[5]  Brad J. Cox,et al.  Object-oriented programming ; an evolutionary approach , 1986 .

[6]  H. Kitano.  Systems Biology: A Brief Overview , 2002, Science.

[7]  Dave Cliff,et al.  The Creatures Global Digital Ecosystem , 1998, Artificial Life.

[8]  David Harel,et al.  Statecharts: A Visual Formalism for Complex Systems , 1987, Sci. Comput. Program..

[9]  Salim Khan,et al.  A multi-agent system for the quantitative simulation of biological networks , 2003, AAMAS '03.

[10]  Tony White,et al.  UML as a cell and biochemistry modeling language. , 2005, Bio Systems.

[11]  Bran Selic,et al.  Real-time object-oriented modeling , 1994, Wiley professional computing.

[12]  Jeff Hardin,et al.  The World of the Cell , 1986 .

[13]  Bernhard Rumpe,et al.  Domain specific modeling , 2005, Software & Systems Modeling.

[14]  Barry McMullin,et al.  SCL: An Artificial Chemistry in Swarm , 1997 .

[15]  M. Tomita.  Whole-cell simulation: a grand challenge of the 21st century. , 2001, Trends in biotechnology.

[16]  Barry McMullin,et al.  Rediscovering Computational Autopoiesis , 1997 .

[17]  David Harel,et al.  On visual formalisms , 1988, CACM.

[18]  David Harel.  A Grand Challenge: Full Reactive Modeling of a Multi-cellular Animal , 2003, HSCC.

[19]  Petr Jan Horn,et al.  Autonomic Computing: IBM's Perspective on the State of Information Technology , 2001 .

[20]  David Harel,et al.  A Grand Challenge: Full Reactive Modeling of a Multi-cellular Animal , 2003, HSCC.

[21]  Amir Pnueli,et al.  Formal Modeling of C. elegans Development: A Scenario-Based Approach , 2003, CMSB.

[22]  H. Maturana,et al.  Autopoiesis: the organization of living systems, its characterization and a model. , 1974, Currents in modern biology.