Three Problems in the Design and Specification of Biomolecular Circuits

Citation

Clamons, Samuel Eric (2022) Three Problems in the Design and Specification of Biomolecular Circuits. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/9b4h-8f95. https://resolver.caltech.edu/CaltechTHESIS:09262021-022402778

Abstract

Programming biological materials is a daunting challenge. Although part of this challenge is practical -- cloning is difficult, synthesizing DNA is expensive at scale, etc. -- a number of the challenges of bioengineering (and synthetic biology in particular) are problems of design and specification. If we could place arbitrary molecules on a surface with perfect precision, what should we place and where? If we could arbitrarily change the genetic content of a cell, even with perfect knowledge of the function and action of every component, what changes would actually enact the functions we want that cell to have? In this thesis, we explore three specific design and specification challenges at three different levels of abstraction, and demonstrate methods for overcoming them. On the level of design language, we use a specialized class of cellular automaton to probe what chemistry can do when restricted to a surface. On the level of \textbf{part specification}, we use several models of CRISPR/Cas9-based transcriptional regulators to understand what dynamic functions those regulators can perform and why, and provide some some suggestions for how to engineer such regulators to more robustly perform those functions. On the level of module design, we consider an easy-to-encounter trap in when modeling a replicating DNA species in a CRN-based biocircuit simulation, for which we suggest a simple, flexible, biologically-plausible workaround.

Thesis Files