Biology Reference
In-Depth Information
4
CHAPTER
From Biological Parts
to Circuit Design
Joao C. Guimaraes
1,2
, Chang C. Liu
1,3
and Adam P. Arkin
1,4
1
University of California, Berkeley, CA, USA
2
University of Minho, Braga, Portugal
3
Miller Institute for Basic Research in Science, Berkeley, CA, USA
4
Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
INTRODUCTION
The last 20 years have witnessed incredible progress in both our understanding of
molecular biological systems and the technologies available for manipulating them. As a
result, biology is quickly expanding from its historical tradition as a discovery-based science
into an engineering science, where biological matter (e.g. RNA, proteins, regulatory circuits,
and cells) is treated as building material for the construction of custom biological function.
This transition has already brought biological solutions to advanced problems in chemical
and pharmaceutical production,
1,2
therapeutics and diagnostics,
3
as well as agricultural and
environmental engineering.
4
In fact, it has originated the new field of synthetic biology.
63
The distinguishing feature of synthetic biology involves the discovery and development
of biological parts, which are genetically encoded modular units with defined biological
function that can be used and reused in different contexts. Once collections of parts
are available, the next level involves their predictable hierarchical assembly into composite
function of greater and greater complexity.
5
In theory, predictable assembly is feasible
as long as parts are well-characterized and behave consistently in a multitude of contexts.
However, it has become clear that parts are not always modular
that is, the functions
of many parts are not neatly encapsulated in the part itself, but rather are significantly
influenced by interactions with different contexts.
6
As a result, many recent efforts in
synthetic biology have focused on the development of strategies to overcome the functional
variability of parts that prevents predictable hierarchical assembly. These strategies include
the establishment of detailed sequence/activity models that provide better predictions of
context effects,
7
10
methods for physically insulating parts from their genetic surroundings
to remove undesired interactions,
11
15
and directed evolution and combinatorial
library screening techniques that use power in numbers to overcome variability.
16
18
Ultimately, the combination of reliable parts sets with these effective strategies for their
predictable functional assembly and rationally tunable function will result in an efficient
design cycle for the construction of complex biological functions to order.
In this chapter, we review the status of the development of standard, reliable parts and their
assembly to create more complex predictable function and propose strategies for
