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Three Problems in the Design and Specification of Biomolecular Circuits


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.


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.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Synthetic biology; biocircuits; molecular biology; molecular nanotechnology.
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Bioengineering
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Murray, Richard M.
Thesis Committee:
  • Winfree, Erik (chair)
  • Rothemund, Paul W. K.
  • Goentoro, Lea A.
  • Murray, Richard M.
Defense Date:17 September 2021
Non-Caltech Author Email:sclamons (AT)
Record Number:CaltechTHESIS:09262021-022402778
Persistent URL:
Related URLs:
URLURL TypeDescription containing some content that appears in Chapter 3 containing some content that appears in Chapter 3 that appears in this thesis as Chapter 2
Clamons, Samuel Eric0000-0002-7993-2278
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14373
Deposited By: Samuel Clamons
Deposited On:14 Oct 2021 19:26
Last Modified:21 Oct 2021 19:06

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