Principles of molecular information processors

Description: Information processing is at the heart of modern technology, and fundamental to life. Investigating molecular information processing serves three purposes: we gain an understanding of living systems; we enhance our ability to engineer and mimic living systems; and through the study of biochemical systems we gain an appreciation of the underlying physics of information. I aim to use biophysical models to explore the principles of information processing in biology.
During the biologically crucial processes of DNA replication, transcription of DNA into RNA and translation of RNA into proteins, a new polymer is produced with a sequence of specific monomers (nucleotides or amino acids) determined by a template. Crucially, this copied polymer must detach from the template and retain the copied sequence. This requirement of "persistence" in copying has major thermodynamic consequences and makes the design of copying systems far subtler than if the copy merely had to self-assemble on the template [1] - so much so that synthetic polymer-copying systems driven purely by chemical free energy are yet to be developed.
Previous work on the creation of persistent polymer copies [1] has been restricted to the simplest case in which each monomer type in the template has a unique analogue in the copy (the polymers have equivalent "alphabets"). However, as in the production of proteins from mRNA, it is possible that multiple distinct monomer types in the template could code for the same monomer type in the copy. Similarly, previous work [1] has ignored the fact that monomer-specific interactions between monomers within the copy, as well as between copy and template, can play a role in determining the sequence produced. The fundamental consequences and opportunities that then arise are unknown. I propose to investigate monomer-specific intra-polymer interactions and "compression" of the monomer alphabet during the production of polymers from a template. The project will first focus on the efficacy of copying and will then consider the possibility of new computational functionality over and above faithful production of persistent copy sequences.
The project will involve constructing and analysing discrete-state biochemical models. Thermodynamic models will be developed first, and then subsequently augmented with consistent kinetics. These models will be studied using tools of statistical physics, information theory and stochastic processes to find the overall thermodynamics, accuracy and efficiency of information processing as a function of system design. Analytic results and limits will be obtained where possible, and simulations and numerical calculations used elsewhere.
[1] Ouldridge and ten Wolde, Phys. Rev. Lett. 118:158103, 2017.