Intro to Engineering Biology

1
Goals of this lecture
You will be able to answer:
● What is synthetic/engineering biology?
● How can I Design, Build, Test, and Learn from biological systems?
● What are the Core Tools of engineering biology?
● How and where can engineering biology be applied to positively impact
society?

You will have:

● Planned a design cycle to approach a current problem
● Learned about engineering biology tools that can help you develop your idea
● Discovered the many sectors that engineering biology can positively impact

Recommended knowledge: “biology 101” level, generally how DNA & cells work 2
Table of Contents
Concept 1-1: What is Synthetic (or Engineering) Biology?
Slides 4-23 - link

Concept 1-2: Engineering Biology Roadmap & the DBTL Cycle

Slides 24-28 - link

Concept 1-3: Core Tools for Engineering Biology

Part 1: Engineering DNA & Biomolecules
Slides 29-48 - link

Concept 1-4: Core Tools for Engineering Biology

Part 2: Engineering Hosts and Data Science
Slides 49-73 - link

Concept 1-5: Impacts & Applications

Slides 74-85 - link 3
 What is Synthetic, or
Concept 1-1 Engineering, Biology?

4
What is Engineering Biology?
Engineering Biology (a broader term for Synthetic Biology) is the design and construction of new biological
entities such as enzymes, genetic circuits, and cells or the redesign of existing biological systems.
Engineering biology builds on the advances in molecular, cell, and systems biology and seeks to transform
biology in the same way that synthesis transformed chemistry and integrated circuit design transformed
computing.
The element that distinguishes engineering biology from traditional molecular and cellular biology is the focus on
the design and construction of core components (e.g., parts of enzymes, genetic circuits, metabolic pathways)
that can be modeled, understood, and tuned to meet specific performance criteria, and the assembly of these
smaller parts and devices into larger integrated systems to solve specific problems.
Unlike many other areas of engineering, biology is incredibly non-linear and less predictable, and there is less
knowledge of the parts and how they interact.
Hence, the overwhelming physical details of natural biology (gene sequences, protein properties, biological
systems) must be organized and recast via a set of design rules that hide information and manage complexity,
thereby enabling the engineering of many-component integrated biological systems.
It is only when this is accomplished that designs of significant scale will be possible.
5
What is Engineering Biology?

The goal: “engineer living cells to do

something useful; for example, treat
a disease, sense a toxic compound
in the environment, or produce a
valuable drug.” (BioBuilder)

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
Bioeconomy. Retrieved from http://roadmap.ebrc.org. doi: 10.25498/E4159B. 6
What is Engineering Biology?
Example: using industrial
biotechnology to treat a disease

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
Bioeconomy. Retrieved from http://roadmap.ebrc.org. doi: 10.25498/E4159B. 7
Industrial: Bacterial production of insulin

Mona Dabbas & Javin Oza, California Polytechnic State University. Created with Biorender.com. 8
Industrial: Bacterial production of insulin
What tools do we need?

● Insulin precursor genes

● Genetic parts for gene expression in E. coli
● Way to assemble these genetic parts
● The E. coli cells themselves
● Way to get the DNA into the cells
● Way to harvest insulin from bacteria
● Way to measure insulin production

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Industrial: Bacterial production of insulin
What steps do we need to take?

● Design a genetic circuit that will produce insulin in E. coli

● Build the genetic circuit, and put it into bacteria
● Test how much insulin is made
● Learn what did/didn’t work, change design accordingly

10
Industrial: Bacterial production of insulin

11
NIH. From DNA to Beer: Harnessing Nature in Medicine & Industry. 2013.
Industrial: Bacterial production of insulin

12
NIH. From DNA to Beer: Harnessing Nature in Medicine & Industry. 2013.
Industrial: Bacterial production of insulin

13
NIH. From DNA to Beer: Harnessing Nature in Medicine & Industry. 2013.
Industrial: Bacterial production of insulin

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NIH. From DNA to Beer: Harnessing Nature in Medicine & Industry. 2013.
What is Engineering Biology?
● Example: use genetic circuits to
mitigate an environmental pest

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
Bioeconomy. Retrieved from http://roadmap.ebrc.org. doi: 10.25498/E4159B. 15
 Environment: Gene drives limit mosquito populations

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Marius Walter, “Gene Drive.” Mona Dabbas & Javin Oza, California Polytechnic State University. Created with Biorender.com.
Environment: Gene drives limit mosquito populations

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Marius Walter, “Gene Drive.”
Environment: Gene drives limit mosquito populations
What tools do we need?

● Gene target to “knock out” or edit

● Genetic tool that will ensure these edits in all offspring
● Way to edit genes in mosquitoes
● Way to measure phenotypic changes from gene edits
● LOTS of safety testing strategies

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Environment: Gene drives limit mosquito populations
What steps do we take?

● Design a system that will knock out the selected gene in all offspring
● Build mosquitoes that carry this system
● Test the safety, efficacy, and spread of this gene system
● Learn by assessing how this impacts the mosquito population, overall
environment, and disease spread

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Environment: Gene drives limit mosquito populations

20
Marius Walter, “Gene Drive.”
Environment: Bioethics of gene drives
Gene Drives: Core Principles:
● What are potential safety concerns of 1. Use engineering biology to benefit
gene drives? the world
2. Weigh benefits of research against
● Who should decide when and where
potential harms
gene drives are used?
3. Incorporate justice into all aspects of
● How can gene drives be contained, or engineering biology
“undone” after use? 4. Share research
5. Protect the freedoms of individuals
and researchers
6. Support open communication
between researchers and other
stakeholders
21
Mackelprang, R., et al. (2021). “Guiding ethical principles in engineering biology research.”
Engineering biology as the next Kondratiev Wave

22
Michael Jewett, Northwestern University.
What is Engineering Biology?
Engineering Biology (aka Synthetic Biology) is the design and construction of new biological entities such as
enzymes, genetic circuits, and cells or the redesign of existing biological systems.
Engineering biology builds on the advances in molecular, cell, and systems biology and seeks to transform
biology in the same way that synthesis transformed chemistry and integrated circuit design transformed
computing.
The element that distinguishes engineering biology from traditional molecular and cellular biology is the focus on
the design and construction of core components (e.g., parts of enzymes, genetic circuits, metabolic pathways)
that can be modeled, understood, and tuned to meet specific performance criteria, and the assembly of these
smaller parts and devices into larger integrated systems to solve specific problems.
Unlike many other areas of engineering, biology is incredibly non-linear and less predictable, and there is less
knowledge of the parts and how they interact.
Hence, the overwhelming physical details of natural biology (gene sequences, protein properties, biological
systems) must be organized and recast via a set of design rules that hide information and manage complexity,
thereby enabling the engineering of many-component integrated biological systems.
It is only when this is accomplished that designs of significant scale will be possible.
23
 Engineering Biology Roadmap
Concept 1-2 & the DBTL Cycle

24
Engineering Biology Roadmap
From a Design, Build, Test, Learn
centered approach

Uses biological, engineering, and

computational tools

To positively impact multiple sectors

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
Bioeconomy. Retrieved from http://roadmap.ebrc.org. doi: 10.25498/E4159B. 25
The DBTL Cycle
Design a biological circuit or system
for a specific function using literature
& computational tools.

Build your system by assembling,

editing, and installing genetic parts.

Test system functionality using

robust metrics & controls.

Learn from how the system (doesn’t)

work to create new design rules, and
share your knowledge.

Gray, P. et al. Synthetic Biology in Australia: An Outlook to

2030 (Australian Council of Learned Academies, 2018). 26
DBTL: In Practice
Design by finding genes for human
insulin precursors, and
optimize/model E. coli expression.

Build gene sequence including

insulin precursor genes though
synthesis & assembly.

Test your circuit in cells by

measuring for insulin precursor
proteins chemically via an assay.

Learn how well your system works,

and what optimization is necessary.
Gray, P. et al. Synthetic Biology in Australia: An Outlook to
2030 (Australian Council of Learned Academies, 2018). 27
DBTL: Exercise
1. Choose a technology or problem that is impactful to you.
2. Think about what an engineering biology solution would look like:
a. What would an initial design of the system look like?
b. What tools and knowledge would you need to build this?
c. How would you test whether your system worked?
d. What might you learn about the problem through testing your solution? What
might be issues when developing your system?
e. And don’t get too bogged down in the details! We’ll go over more tools for each
phase later.

Example ideas: trees with fireproof wood, drought-resistant cabbage, sustainable bioplastics,
engineered probiotics for gut health, cell-free water quality sensors

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 Core Tools Part 1:
Concept 1-3 Engineering DNA,
Biomolecular Engineering

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Core Tools for Engineering DNA
● What are the current tools for engineering DNA?
● Tools enabling a engineering DNA DBTL
○ Synthesis
○ Sequencing
○ Standardization
○ Assembly
○ Editing

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
Bioeconomy. Retrieved from http://roadmap.ebrc.org. doi: 10.25498/E4159B. 30
Engineering DNA:
Synthesis and Sequencing
● Gene synthesis and
sequencing are becoming
exponentially cheaper
● Entire genes can be
synthesized in a matter of
hours-days at relatively low
cost
● This rapid reduction in cost
and time for sequencing and
synthesis allows large-scale
testing of new genetic
constructs Carlson, R. Synthesis. “On DNA and transistors.”
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Engineering DNA:
How single-stranded DNA is synthesized
● Phosphoramidite chemical synthesis
○ Pioneered by Marvin Caruthers in 1983 at CU-Boulder
● Single-stranded DNA oligos are synthesized using solid-phase chemistry
performed on solid supports
○ Controlled pore glass beads (IDT, GenScript)
○ Silicon chip (Twist, Agilent)

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Twist Bioscience. Twist Bioscience.
Engineering DNA:
How double-stranded genes are synthesized
● Larger genes can be constructed
using polymerase chain
assembly of shorter synthetic
fragments
● Short single-stranded oligos are
stitched together and filled in
using DNA polymerase and PCR
to produce double-stranded
genes

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Dhorspool, “PCA polymerase cycling assembly.”
Engineering DNA:
Standardized depiction of gene circuits
● Engineering Biology often requires
descriptions of the DNA sequences
used and how they function
● With the wealth of easy to
synthesize DNA parts how do we
communicate what pieces of
synthetic DNA do?
● The Synthetic Biology Open
Language (SBOL) is a framework
for describing synthetic DNA
sequences and their functional
relationships Joshua Atkinson, University of Southern California 34
Engineering DNA:
Examples of SBOL based diagrams
● On the left is a plasmid for
chemically-inducible expression red
fluorescent protein
● On the right is a plasmid for the
light-inducible expression of the
adhesins CdrAB
● Both of these plasmids express
components that control the
expression of other components
● The logical interpretations of the
diagrams are listed below the
image. Joshua Atkinson, University of Southern California 35
Engineering DNA:
DNA assembly methods

● There are a range of techniques for assembling genetic parts into genetic
constructs and plasmids in vitro
○ Classical assembly (restriction enzyme + ligation)
○ Golden gate assembly
○ Gibson assembly 36
Joshua Atkinson, University of Southern California
Engineering DNA:
DNA assembly using Classical Assembly
● This approach has been used for
BioBrick Cloning using Classical Assembly
vector cloning in molecular biology
since the 1970s (Cohen SN, et al.
PNAS (1973)70(11):3240-4)
● Type II restriction enzymes (RE)
cut dsDNA typically within 6 bp
palindromic sequences leaving 4 bp
ssDNA overhangs
● Complementary overhangs can be
ligated together using a DNA ligase
● This is also used in BioBrick cloning
(EcoRI/XbaI, SpeI/PstI)
● Leaves behind RE site scars
37
between DNA parts Joshua Atkinson, University of Southern California
Engineering DNA:
Multipart assembly using Golden Gate
● To overcome the limitation of scar sites
and to improve ligation efficiency
Golden Gate cloning was developed in
2008 (Engler C, et al., PLoS One (2008)
3(11):e3647)
● Type IIs restriction enzymes bind
recognition sites, but cut outside of
them
● This allows for the generation of
programmable overhangs that eliminate
scare sites between DNA parts and do
not reform the original cut site
improving efficiency
38
Joshua Atkinson, University of Southern California
Engineering DNA:
Multipart assembly using Golden Gate
● Golden Gate assembly can be easily
achieved using PCR with primers that
introduce Type IIs restriction sites (e.g.,
BsaI, BbsI, Esp3I) that flank parts
● Parts have unique complementary
overhangs (OH1-4) that guide their
assembly in the correct order
● This can be scaled to >50 fragments
allowing for high-throughput multipart
assembly

39
Joshua Atkinson, University of Southern California
Engineering DNA:
Multipart assembly using Gibson Assembly
● To facilitate large-scale DNA assembly
in 2009 Gibson DNA assembly was
developed (Gibson D.G., et al., Nat. Methods
(2009) 6(5)343-345)
● This method utilizes in vitro
homologous recombination facilitated
by T5 exonuclease, Phusion
polymerase, and Taq ligase
● This requires the introduction of ~40-60
bp of overlapping sequences (OS) on
the ends of the sequences to guide DNA
parts to assemble
● Has been scaled to assembly of entire
40
genomes Joshua Atkinson, University of Southern California
Engineering DNA:
High-throughput combinatorial DNA assembly
● The use of multi-part DNA assembly
techniques enables the construction
of large scale combinatorial libraries
of DNA sequences
● This is useful when optimizing
expression of multiple genes at once
allowing for rapid exploration of
parameter spaces
● This approach is often used for
enhancing yield of metabolic
pathways and engineering proteins

41
Joshua Atkinson, University of Southern California
Engineering DNA:
Editing Genomes by Knocking-IN or Knocking-OUT
● Genomes can also be engineered
● One strategy for genome editing is to
leverage homologous recombination to
delete genes (Knock-OUT) or to
introduce entirely new sequences
(Knock-IN)
● This can be achieved by introducing
selective markers to select for cells
within populations that have either
gained (positive selection) or lost the
engineered DNA (negative selection)

42
Joshua Atkinson, University of Southern California
Engineering DNA:
Using Recombineering to edit genomes
● Viral mechanisms for DNA integration
have been co-opted to increase
genomic engineering efficiency
● One approach, called ‘recombineering’,
leverages the E. coli lambda prophage
(Yu D, et al., PNAS (2000), 97(11):5978-5983)
● Prophage proteins Exo, Beta, and Gam
improve integration of DNA harboring
genomic overlapping sequences by
chewing back dsDNA to generate
ssDNA, protecting ssDNA from
degradation, and blocking host
exonucleases, respectively
43
Joshua Atkinson, University of Southern California
Engineering DNA:
Using CRISPR-Cas9 to make precise genome edits
● Adaptive-immunity mechanisms from bacteria have
been co-opted to enable precise genomic edits
● Clustered Regularly Interspaced Short Palindromic
(CRISPR) systems from diverse bacteria have
enabled a revolution in genomic editing
● Cas9 is one of the most widely used CRISPR systems
used for genome engineering (Jinek M., et al., Science
(2012) 337(6096):816-821)
● Cas9 is an RNA-guided endonuclease that makes
double-stranded breaks at specific sites.
● Guide RNAs (gRNA) can be engineered target Cas9 to
specific DNA sequences that precede PAM sites
(NGG).
● One way to make genomic edits leverages homology
directed repair to integrate an engineered repair
template that eliminates the PAM site and
subsequent retargeting.
44
Joshua Atkinson, University of Southern California
Core Tools for Biomolecular Engineering
● What are our current tools for
Biomolecular Engineering?
● Tools enable a Biomolecular
Engineering DBTL
○ Comprehensive Mutagenesis libraries
○ Functional Screens
○ Functional Selections
○ Directed Evolution

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
Bioeconomy. Retrieved from http://roadmap.ebrc.org. doi: 10.25498/E4159B. 45
Biomolecular Engineering:
Natural Macromolecules
● Natural macromolecules including
proteins and RNAs can be engineered to
have new properties (e.g.,
thermostability) or perform new
functions (e.g., binding, catalysis)
● Directed evolution can be used to tailor
the function of proteins through rounds
of sequence diversification, selection
for function, and amplification of

46
The Nobel Prize.
Biomolecular Engineering:
Unnatural Macromolecules
● Entirely new protein sequences not
seen in nature can be generated
through de novo protein design
● De novo design enables exploration
of protein sequence space beyond
what nature has itself explored

47
Pan X. and Kortemme T. JBC Reviews (2021) 296 100558
Biomolecular Engineering:
Circuits and Pathways
● In addition to individual
biomolecules large scale
networks of biomolecules
● Novel metabolic pathways can
be constructed using
retrosynthesis approaches
● Combinatorial libraries can be
used to optimize expression of
pathways proteins
● Adaptive laboratory evolution
can be used to optimize the
host genome for improved
yield of a target molecule
48
Gurdo N., Volke D.C., Nikel P.I. (2022) Trends in Biotechnology
 Core Tools Part 2:
Concept 1-4 Host Engineering,
Data Science

49
Core Tools for Host Engineering
● What types of hosts are there?
● Model & non-model systems
● Thinking across scales

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
Bioeconomy. Retrieved from http://roadmap.ebrc.org. doi: 10.25498/E4159B. 50
Host Engineering
Host choice - what can systems do?
Cell-free Bacteria Yeast

● Can quickly test ● Grows well in bulk ● Grows well in bulk

gene expression ● Model for many ● Can produce a
● Grow compounds diseases variety of proteins
too taxing for cells ● Prokaryotic ● Often used in
● Needs to be ● Can’t fold many foods (i.e. bread)
extracted, purified human proteins
51
Created with Biorender.com.
Host Engineering
Host choice - what can systems do?
Mammal Plant Whole organism

● Human protein ● Photosynthetic ● Increased complexity

folding ● Produce a variety ● Can study
● Test drug of compounds phenotypes in vivo
therapies ● Fewer tools ● More difficult to
● Difficult to grow in available engineer at the cell
bulk level
52
Created with Biorender.com.
Host Engineering
“Model organism”: well-studied, often engineering tools available, widely used

When to use a model organism When to use a non-model organism

● Maximizing production a compound ● Studying a specific process in its

that can be made in a model system native context
● Looking to use a specific, established ● Making complex or unusual proteins
tool or platform ● Looking for specific, niche host
● A known model organism is a good characteristics
fit for the project you want to do

53
Host Engineering
Example: producing human ion channels in bulk (for crystallography or drug
discovery)
If you use a model human cell strain… If you use non-model Tetrahymena…

● Easy to get in correct genes inserted ● More difficult to insert genes

● Difficult to produce in non-neural ● Can produce in large quantities
cells, or large quantities ● Can grow in bulk (if you have the
● Cannot grow easily in bulk specific expertise to work with it)

54
Created with Biorender.com.
Host Engineering:
Engineering across scale
● Very few cells are naturally isolated
● Cell tissues and microbial consortia are
complex
○ Often more difficult to engineer
○ Can carry out complex tasks
● Can give better understanding of natural
systems

55
Created with Biorender.com.
Host Engineering:
Tissue scale
● Example: humanized organs in pigs
for xenotransplantation
Created with
● Can edit genes in pigs to prevent Biorender.com.

human immune rejection

● Requires initial transplant of human
cells to start
● Often use existing systems with
some de novo engineered parts

56
Nagashima & Matsunari. (2016). Theriogenology.
Host Engineering:
Consortia scale
Created with
● Example: engineered live Biorender.com.
biotherapeutic products to protect
the microbiome from antibiotics
● Allows antibiotic to clear pathogen
from bloodstream, without harm to
native gut microbiota
● Specific changes that lead to
known broader outcomes

57
Wyss Institute at Harvard University.
Host Engineering:
Engineering across scale
● Beyond tissues are organisms
○ High-level, complex interactions
and functions
○ Often limited to making singular,
distinct edits
● Beyond consortia are ecosystems
○ Many consortia and organisms
interacting
○ Potential for “terraforming”
○ Difficult to recapitulate in lab

58
Created with Biorender.com.
Host Engineering:
Organism scale
● Example: use of CRISPR to treat
sickle cell anemia
● Modification of one codon can
revert to non-sickle phenotype
● Specific, targeted changes

59
Sürün, et al. (2018). Drug Discovery Today: Technologies.
Host Engineering:
Ecosystem scale
● Example: Using of gene drives to Created with
Biorender.com.
suppress pest populations
● Recall introduction!
● Also for specific, targeted changes

60
Mariuswalter, “Gene Drive.”
Core Tools for Data Science
● What data is out there?
● Modeling & Machine Learning
● Automation

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
Bioeconomy. Retrieved from http://roadmap.ebrc.org. doi: 10.25498/E4159B. 61
Data Science:
“Omics data”
Genome Transcriptome Proteome Metabolome
Who is there? What are they What are they What are they
What can they make? saying to making? making? doing?

● Species ● Gene regulation ● RNA regulation ● Metabolic

identification ● Population ● Protein stability & pathway efficiency
● Mutation rate in a heterogeneity degradation ● Cellular inputs &
population outputs

Then integrate!
62
Created with Biorender.com.
Data Science:
Genomics

● Why: ● How:
○ Discover members of a large ○ Large-scale sequencing
population ○ Reassembly (what pieces
○ Understand the variation are from whom)
between/within populations ○ Comparing regions of
○ Epigenomics: how DNA interest (species identifiers,
modifications impact important coding regions)
expression

63
Created with Biorender.com.
Data Science:
Transcriptomics

● Why: ● How:
○ mRNA - what genes are cells ○ RNA sequencing (similar to
expressing under specific DNA-seq)
conditions ○ Microarrays (quantify a set
○ ncRNA - regulation and more of specific sequences)

64
Created with Biorender.com.
Data Science:
Proteomics

● Why: ● How:
○ Know what proteins make up a ○ Immunoassays (antibodies)
cell/tissue ○ Protein purification (pull out
○ Know if cells are making a and quantify a protein of
product of interest interest, often through a tag)
○ Mass spectrometry (look for
proteins with known
chemical profiles)

65
Created with Biorender.com.
Data Science:
Metabolomics

● Why: ● How:
○ Know what chemical products ○ Spectrometry methods
a cell is making (gas/liquid chromatography)
○ Quantify signalling molecules ○ Assays for specific
or chemical product molecules of interest
production

66
Created with Biorender.com.
Data Science:
Databases

● National Center for Biotechnology

Information (NCBI)
○ GenBank - NIH genetic seq. collection
○ Nucleotide BLAST - search gene seqs.
● UniProt
○ Protein seq. and functional information
● RCSB Protein Database (PDB)
○ Characterized protein structure and
models
● Other, more specific DBs:
○ FPBase - fluorescent protein
characterization and lineages
67
Data Science:
Modeling genetic parts

● Can use first principles

thermodynamics to predict function
of parts in some cases
● Can integrate larger datasets with
machine learning models to make Predict RBS output based on both
RBS and protein sequence
more sophisticated predictions

68
Data Science:
Modeling proteins (AlphaFold)

69
Kep17, “Amino acid chains.” DeepMind.
Data Science:
Modeling whole systems
● Quantify what is there (-omics)
● Determine inputs and outputs
● Apply equations to determine
system functions - metabolic
efficiency, protein activity, etc.
● NIH: ‘Systems biology is an
approach to understand the larger
picture—be it at the level of the
organism, tissue, or cell—by putting
its pieces together. ‘

70
Karr, et al. (2012). Nucleic acids research.
Data Science:
Automation of design

● CAD (Computer-Aided Design) of

gene constructs
● Automation of gene synthesis

71
De Novo DNA, “RBS Library Calculator.”
Data Science:
Automation of laboratory processes

● Liquid handlers to automate

Building & Testing genetic
constructs
● Increase throughput to test multiple
constructs simultaneously
● Integrated analysis for -omics

72
Created with Biorender.com.
Data Science:
Automation of laboratory processes

73
OpenTrons.
Concept 1-5 Impacts & Applications

74
Engineering Biology
Impacts & Applications
We group the impacts of
Engineering Biology into five major
sectors:

● Industrial Biotechnology
● Environmental Biotechnology
● Food & Agriculture
● Health & Medicine
● Energy

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
Bioeconomy. Retrieved from http://roadmap.ebrc.org. doi: 10.25498/E4159B. 75
Food & Agriculture
Microbial symbiont fertilizers

● Plants need nitrogen in the soil to grow - often from fertilizer

● Current methods to make nitrogen-rich fertilizers use large amounts of energy
and have many negative environmental impacts
● Some microbes are great at fixing nitrogen - can we engineer microbes to
grow on plant roots and fix nitrogen for us?

76
Food & Agriculture

77
Pivot Bio.
Health & Medicine
At-home water quality testing

● Clean water is vital for health - need fast, accurate, affordable assessment
● Many possible contaminants (pathogens, heavy metals, pharmaceuticals)
● ROSALIND - cell-free diagnostic that combines natural sensor machinery with
human-readable fluorescent or colorimetric output of water quality

78
Jung, J.K., Archuleta, C.M., Alam, K.K. et al. Nat Chem Biol 18, 385–393 (2022).
Health & Medicine

79
Northwestern U.
Energy
Carbon-neutral fuels for circular economies
● Microbial metabolism can be
engineered to turn cells into
chemical factories to meet the
needs of human resources
● Using the core-tools of
engineering biology, cells can be
engineered to use simple
feedstocks like CO2, CO, H2 and
turn these into useful products
with lower carbon impacts than
conventional fossil fuel derived
alternatives. 80
Liew F., et al. (2016) Front. Microbiol. 7:694.
Energy
Carbon-neutral fuels for circular economies

81
LanzaTech.
Career Sectors in Engineering Biology
● Each sector has its own culture, pacing, and roles
● Academia: tenure-track PI, lecturer, core facility manager
● Government: national lab scientist, funding agency program manager, admin
● Industry: research scientist, customer support, consultant
● Between & beyond:
○ Science communication, journalism
○ Patent lawyer, tech transfer specialist
○ Policy, regulations, governance
● Explore digital resources:
○ EBRC In Translation podcast
○ BioBuilder Life-Changing Science podcast
○ AAAS myIDP website
82
Diverse Careers in Engineering Biology

83
Hinman, A.W., Friedman, D.C. EBRC. (2022).
Engineering Biology is driven by
a collaborative network of dedicated professionals

Many possible roles:

Bioinformatician in an academic lab who applies data analysis, modeling, and

statistics to large datasets to delineate complex biological processes.

Program manager in a government agency who develops and writes research &
training initiatives, and discusses research priorities with academic labs.

Biosecurity specialist in a biotech company who coordinates the development

and operation of security screening processes.

84
Summary
Engineering biology:

● Uses a DBTL framework

● To apply key biology &
engineering technologies
● For impact in sectors across
aspects of life and the planet

Engineering Biology Research Consortium (2019). Engineering Biology: A Research Roadmap for the Next-Generation
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Credits
Slides developed by Joshua Atkinson & Michael Sheets.

We thank the EBRC Education Working Group for helpful feedback on the slides,
and in particular thanks to Emily Aurand, Kaitlyn Duvall, India Hook-Barnard, Javin
Oza, Beth Vitalis, and Michael Jewett.

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Figure Credits
6. EBRC. (2019). “Engineering Biology: A Research Roadmap for the Next-Generation Bioeconomy.” (Recurring.)
8. Dabbas, M., & Oza, J. Original graphic created with BioRender.com.
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design–build–test–learn cycle of nontraditional microbes.” Trends in Biotechnology. doi:10.1016/j.tibtech.2022.03.004
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57. Boettner, B. (2022). “Protecting the human intestinal microbiome with synthetic biology.” Wyss Institute at Harvard
University.
59. Sürün, D., von Melchner, H., & Schnütgen, F. (2018). CRISPR/Cas9 genome engineering in hematopoietic cells. Drug
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69 right. DeepMind. (2020). “AlphaFold: a solution to a 50-year-old grand challenge in biology.”
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for comprehensive whole-cell models. Nucleic acids research, 41(D1), D787-D792.
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Extended Resources
EBRC video playlist: https://youtube.com/playlist?list=PLf4eUKhxEIurvaNwNSpyXlKf_LoFRlZZm

iBiology Synthetic Biology course: https://www.ibiology.org/playlists/synthetic-biology/

Raj Lab Synbio Transcript course: https://youtu.be/3xJI8j7YlrI

EBRC Synthetic Biology & Machine Learning series: https://ebrc.org/synbio-ml-education/

CalTech Biomolecular Feedback Systems resource: http://www.cds.caltech.edu/~murray/BFSwiki/index.php

Ben Thuronyi Designing and Building Synthetic Biology Constructs resource: http://bit.ly/synbioguide or
https://docs.google.com/document/d/1k3H1xBC_gu_F0B6lPPZeSilcfYtxn4o7bkbBUT_McTc/edit

BioBuilder courses and content: https://biobuilder.org/

Paper: Dymond JS, et al. (2009). Teaching synthetic biology, bioinformatics and engineering to undergraduates: the
interdisciplinary Build-a-Genome course. Genetics, 181(1), 13-21. https://doi.org/10.1534/genetics.108.096784

Paper: Williams LC et al. (2020). The genetic code kit: an open-source cell-free platform for biochemical and biotechnology
education. Frontiers in bioengineering and biotechnology, 8, 941. https://doi.org/10.3389/fbioe.2020.00941
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