Grant: Discovery Grants Program - Individual

Three centuries ago, the development of calculus laid the foundation for the formalization of physics. Information and computational science is now well-positioned to assist in the creation of an analogous formal framework for reasoning about biological processes in a rigorous way. The long-term goals of the research proposed here fall into the emerging discipline of Natural Computing and will help to lay these formal foundations for biological processes. Moreover, by studying theoretical models based on natural rules, rather than artificial human-generated rules, we open new insights into the very nature of computation itself. In the short-term, we propose two projects: The genome of the microscopic worm C. elegans has roughly the same number of genes as the human genome; yet, we observe apparently different levels of complexity in these two organisms. One explanation for this dichotomy is that genes can undergo alternative processing events that modify them, allowing a single gene to encode multiple proteins. One such processing event is that of frameshifting during translation. We have modelled frameshift events as a computation and propose to study this model both to uncover the formal properties of frameshifting as well as develop efficient algorithms for detecting, simulating and experimenting with frameshifting in real genomes. The minimization of free energy in a biochemical system is the primary force driving chemical reactions including complex macromolecular behaviours. Most existing models in Natural Computing have thus far abstracted away from such thermodynamic considerations. We propose to develop a general framework for introducing thermodynamic considerations to formal models, allowing them to reflect more closely the underlying physical system under study and providing a novel model of computation.