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UBC Theses and Dissertations

Epigenetic information in the cell : a potential avenue for biocompatible computing Hentrich, Thomas


Living organisms sense, process and produce molecular signals to regulate their activity and, thus, process information and perform computations on biological substrates. Understanding the fundamental principles of information representation and manipulation along these algorithmic bioprocesses will advance our understanding of biology and inspire novel forms of computation. From one side of this connection, the research field of Bioinformatics uses computational tools to gain insight into the processes of life. On the other side, Biomolecular Computing attempts to utilize molecules and cellular machineries to operate engineered nano-scale biocomputers in live cells for diagnostics, therapeutics and many other applications in biotechnology, bioengineering and biomedicine. Addressing this bifold character of information of life, this thesis contributes to the part of Computing Life by elucidating aspects of chromatin, the nucleo-protein structure of DNA in the cell. As a computation and storage layer chromatin offers a high degree of plasticity to integrate (environmental) signals into DNA-based regulation and allows information propagation according to epigenetic principles. In this work, I present results on the complexity of chromatin modifications and reveal their impact on gene activity and related cellular functions. I further discuss a bioinformatics pipeline I developed and that was applied for genome-wide chromatin profiling and transcriptome analysis. From the perspective of Living Computers, I address the question of information encoding by biomolecules and draw on principles of epigenetics to devise a model for an RNA interference-based equivalent of the electric flip-flop, which is one of the fundamental elements in digital circuits. In particular, I focus on the digital switch abstraction of the flip-flop as it is the pivotal idea in both the electric and biomolecular world that connects and at the same time decouples an underlying physical process and the abstract representation of information. This work contributes elucidating the computational principles of the RNA interference machinery and suggests novel ideas for universal memory units in biomolecular computing. By juxtaposing both the natural and artificial perspective, this thesis attempts to enhance our understanding of epigenetic information processing in the cell and its capacity for biocomputing applications.

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