synthetic biology blends math, computer science, and biology a. malcolm campbell reed college march...
TRANSCRIPT
![Page 1: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/1.jpg)
Synthetic Biology Blends Math, Computer Science, and Biology
A. Malcolm Campbell
Reed CollegeMarch 7, 2008
![Page 2: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/2.jpg)
What is Synthetic Biology?
![Page 3: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/3.jpg)
BioBrick Registry of Standard Parts
http://parts.mit.edu/registry/index.php/Main_Page
![Page 4: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/4.jpg)
Peking University Imperial College
What is iGEM?
![Page 5: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/5.jpg)
Davidson CollegeMalcolm Campbell (bio.)Laurie Heyer (math)Lance HardenSabriya Rosemond (HU)Samantha SimpsonErin Zwack
Missouri Western State U.Todd Eckdahl (bio.)Jeff Poet (math)Marian BroderickAdam BrownTrevor ButnerLane Heard (HS student)Eric JessenKelley MalloyBrad Ogden
SYNTHETIC BIOLOGYiGEM 2006
![Page 6: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/6.jpg)
Enter: Flapjack & The Hotcakes
Erin Zwack (Jr. Bio); Lance Harden (Soph. Math); Sabriya Rosemond (Jr. Bio)
![Page 7: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/7.jpg)
Erin Zwack (Jr. Bio); Lance Harden (Soph. Math); Sabriya Rosemond (Jr. Bio)
Enter: Flapjack & The Hotcakes
![Page 8: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/8.jpg)
Wooly Mammoths of Missouri Western
![Page 9: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/9.jpg)
1234
Burnt Pancake Problem
![Page 10: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/10.jpg)
Burnt Pancake Problem
![Page 11: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/11.jpg)
Burnt Pancake Problem
![Page 12: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/12.jpg)
Look familiar?
![Page 13: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/13.jpg)
![Page 14: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/14.jpg)
How to Make Flippable DNA Pancakes
hixCRBSRBS
hixC
TetTet
hixCpBad
pancake 1 pancake 2
![Page 15: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/15.jpg)
Flipping DNA with Hin/hixC
![Page 16: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/16.jpg)
Flipping DNA with Hin/hixC
![Page 17: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/17.jpg)
Flipping DNA with Hin/hixC
![Page 18: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/18.jpg)
How to Make Flippable DNA Pancakes
All on 1 Plasmid: Two pancakes (Amp vector) + Hin
hixCRBSRBS
hixC
TetTet
hixCpBad
pancake 1 pancake 2
TT TT
pLac
RBSRBS Hin LVAHin LVA
![Page 19: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/19.jpg)
Hin Flips DNA of Different Sizes
![Page 20: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/20.jpg)
Hin Flips Individual Segments
-2 1
![Page 21: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/21.jpg)
No Equilibrium 11 hrs Post-transformation
![Page 22: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/22.jpg)
Hin Flips Paired Segments
white light u.v.
mRFP off
mRFP on double-pancake flip
-2 1
2-1
![Page 23: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/23.jpg)
Modeling to Understand Flipping
( 1, 2)(-2, -1)
( 1, -2)(-1, 2)(-2, 1)( 2, -1)
(-1, -2)( 2, 1)
(1,2) (-1,2)
(1,-2) (-1,-2)
(-2,1)(-2,-1)
(2,-1) (2,1)
![Page 24: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/24.jpg)
( 1, 2)(-2, -1)
( 1, -2)(-1, 2)(-2, 1)( 2, -1)
(-1, -2)( 2, 1)
(1,2) (-1,2)
(1,-2) (-1,-2)
(-2,1)(-2,-1)
(2,-1) (2,1)
1 flip: 0% solved
Modeling to Understand Flipping
![Page 25: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/25.jpg)
( 1, 2)(-2, -1)
( 1, -2)(-1, 2)(-2, 1)( 2, -1)
(-1, -2)( 2, 1)
(1,2) (-1,2)
(1,-2) (-1,-2)
(-2,1)(-2,-1)
(2,-1) (2,1)
2 flips: 2/9 (22.2%)solved
Modeling to Understand Flipping
![Page 26: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/26.jpg)
PRACTICAL
Proof-of-concept for bacterial computers
Data storagen units gives 2n(n!) combinations
BASIC BIOLOGY RESEARCH
Improved transgenes in vivo
Evolutionary insights
Consequences of DNA Flipping Devices -1,2 -2,-1
in 2 flips!
genegeneregulatorregulator
![Page 27: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/27.jpg)
Success at iGEM 2006
![Page 28: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/28.jpg)
Living Hardware to Solve the Hamiltonian Path Problem,
2007
Faculty: Malcolm Campbell, Todd Eckdahl, Karmella Haynes, Laurie Heyer, Jeff Poet
Students: Oyinade Adefuye,
Will DeLoache, Jim Dickson,
Andrew Martens, Amber Shoecraft, and Mike Waters; Jordan Baumgardner, Tom
Crowley, Lane Heard, Nick Morton, Michelle Ritter, Jessica Treece,
Matt Unzicker, Amanda Valencia
![Page 29: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/29.jpg)
The Hamiltonian Path Problem
1
3
5
4
2
![Page 30: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/30.jpg)
1
3
5
4
2
The Hamiltonian Path Problem
![Page 31: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/31.jpg)
Advantages of Bacterial Computation
Software Hardware Computation
Computation
Computation
![Page 32: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/32.jpg)
Advantages of Bacterial Computation
Software Hardware Computation
Computation
Computation
$
¢
![Page 33: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/33.jpg)
Cell Division
• Non-Polynomial (NP)
• No Efficient Algorithms
# of
Pro
cess
ors
Advantages of Bacterial Computation
![Page 34: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/34.jpg)
3
Using Hin/hixC to Solve the HPPUsing Hin/hixC to Solve the
HPP
1 54 34 23 41 42 53 14
1
3
5
4
2
![Page 35: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/35.jpg)
3
Using Hin/hixC to Solve the HPP
1 54 34 23 41 42 53 14
hixC Sites
1
3
5
4
2
Using Hin/hixC to Solve the HPP
![Page 36: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/36.jpg)
Using Hin/hixC to Solve the HPP
1
3
5
4
2
Using Hin/hixC to Solve the HPP
![Page 37: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/37.jpg)
Using Hin/hixC to Solve the HPP
1
3
5
4
2
Using Hin/hixC to Solve the HPP
![Page 38: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/38.jpg)
Using Hin/hixC to Solve the HPP
1
3
5
4
2
Using Hin/hixC to Solve the HPP
![Page 39: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/39.jpg)
Solved Hamiltonian Path
1
3
5
4
2
Using Hin/hixC to Solve the HPP
![Page 40: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/40.jpg)
How to Split a Gene
RBSRBS
Promoter
ReporterReporter
hixCRBSRBS
Promoter
Repo- Repo- rter
Detectable Phenotype
Detectable Phenotype
?
![Page 41: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/41.jpg)
Gene Splitter Software
Input Output
1. Gene Sequence (cut and paste)
2. Where do you want your hixC site?
3. Pick an extra base to avoid a frameshift.
1. Generates 4 Primers (optimized for Tm).
2. Biobrick ends are added to primers.
3. Frameshift is eliminated.
http://gcat.davidson.edu/iGEM07/genesplitter.html
![Page 42: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/42.jpg)
Gene-Splitter Output
Note: Oligos are optimized for Tm.
![Page 43: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/43.jpg)
Predicting Outcomes of Bacterial Computation
![Page 44: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/44.jpg)
Pro
babi
lity
of H
PP
Sol
utio
n
Number of Flips
4 Nodes & 3 Edges
Starting Arrangements
![Page 45: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/45.jpg)
k = actual number of occurrences
λ = expected number of occurrences
λ = m plasmids * # solved permutations of edges ÷ # permutations of edges
Cumulative Poisson Distribution:
P(# of solutions ≥ k) =
€
1−e−λ • λ x
x!x=0
k−1
∑
k = 1 5 10 20
m = 10,000,000 .0697 0 0 0
50,000,000 .3032 .00004 0 0
100,000,000 .5145 .0009 0 0
200,000,000 .7643 .0161 .000003 0
500,000,000 .973 .2961 .0041 0
1,000,000,000 .9992 .8466 .1932 .00007
Probability of at least k solutions on m plasmids for a 14-edge graph
How Many Plasmids Do We Need?
![Page 46: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/46.jpg)
False Positives
Extra Edge
1
3
5
4
2
![Page 47: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/47.jpg)
PCR Fragment Length
PCR Fragment Length
1
3
5
4
2
False Positives
![Page 48: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/48.jpg)
Detection of True Positives
0
0.25
0.5
0.75
1
4/6 6/9 7/12 7/14
# of
Tru
e P
ositi
ves
÷
Tot
al #
of P
ositi
ves
# of Nodes / # of Edges
1.00
10.00
100.00
1000.00
10000.00
100000.00
1000000.00
10000000.00
100000000.00
4/6 6/9 7/12 7/14
# of Nodes / # of Edges
Total # of Positives
# of Nodes / # of Edges
Tot
al #
of P
ositi
ves
![Page 50: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/50.jpg)
Choosing Graphs
Graph 2
A
B
D
Graph 1
A
B
C
![Page 51: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/51.jpg)
Splitting Reporter Genes
Green Fluorescent Protein Red Fluorescent Protein
![Page 52: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/52.jpg)
GFP Split by hixC
Splitting Reporter Genes
RFP Split by hixC
![Page 53: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/53.jpg)
HPP Constructs
Graph 1 Constructs:
Graph 2 Construct:
AB
ABC
ACB
BAC
DBA
Graph 0 Construct:
Graph 2
Graph 1
B
AC
A D
B
Graph 0
B
A
![Page 54: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/54.jpg)
T7 RNAP
Hin + Unflipped
HPP
TransformationPCR to
Remove Hin
& Transform
Coupled Hin & HPP Graph
![Page 55: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/55.jpg)
Flipping Detected by Phenotype
ACB
(Red)
BAC(None)
ABC(Yellow)
![Page 56: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/56.jpg)
Hin-Mediated FlippingACB
(Red)
BAC(None)
ABC(Yellow)
Flipping Detected by Phenotype
![Page 57: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/57.jpg)
ABC Flipping
Yellow
HinYellow, Green, Red, None
![Page 58: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/58.jpg)
Red
ACB Flipping
HinYellow, Green, Red, None
![Page 59: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/59.jpg)
BAC Flipping
Hin None
Yellow, Green, Red, None
![Page 60: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/60.jpg)
Flipping Detected by PCR
ABC
ACB
BAC
Unflipped Flipped
ABCACB
BAC
![Page 61: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/61.jpg)
Flipping Detected by PCR
ABC
ACB
BAC
Unflipped Flipped
ABCACB
BAC
![Page 62: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/62.jpg)
RFP1 hixC GFP2
BAC
Flipping Detected by Sequencing
![Page 63: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/63.jpg)
RFP1 hixC GFP2
RFP1 hixC RFP2
BAC
Flipped-BAC
Flipping Detected by Sequencing
Hin
![Page 64: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/64.jpg)
Conclusions
• Modeling revealed feasibility of our approach
• GFP and RFP successfully split using hixC
• Added 69 parts to the Registry
• HPP problems given to bacteria
• Flipping shown by fluorescence, PCR, and sequence
• Bacterial computers are working on the HPP and may have solved it
![Page 65: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/65.jpg)
Living Hardware to Solve the
Hamiltonian Path Problem
Acknowledgements: Thanks to The Duke Endowment, HHMI, NSF DMS 0733955, Genome Consortium for Active Teaching, Davidson College James G. Martin
Genomics Program, Missouri Western SGA, Foundation, and Summer Research Institute, and Karen Acker (DC ’07). Oyinade Adefuye is from North Carolina Central
University and Amber Shoecraft is from Johnson C. Smith University.
![Page 66: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/66.jpg)
What is the Focus?
![Page 67: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/67.jpg)
Thanks to my life-long collaborators
![Page 68: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/68.jpg)
![Page 69: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/69.jpg)
DNA Microarrays:windows into a functional
genome
Opportunities for Undergraduate Research
![Page 70: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/70.jpg)
How do microarrays work?
![Page 71: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/71.jpg)
How do microarrays work?
![Page 72: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/72.jpg)
How do microarrays work?
![Page 75: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/75.jpg)
How Can Microarrays be Introduced?
Ben Kittinger ‘05
Wet-lab microarray simulation kit - fast, cheap, works every time.
![Page 76: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/76.jpg)
How Can Students Practice?
www.bio.davidson.edu/projects/GCAT/Spot_synthesizer/Spot_synthesizer.html
![Page 77: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/77.jpg)
What Else Can Chips Do?
Jackie Ryan ‘05
![Page 78: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/78.jpg)
Comparative Genome Hybridizations
![Page 79: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/79.jpg)
Extra Slides
![Page 80: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/80.jpg)
![Page 81: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/81.jpg)
Can we build a biological computer?
The burnt pancake problem can be modeled as DNA
(-2, 4, -1, 3) (1, 2, 3, 4)
DNA Computer Movie >>
![Page 82: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/82.jpg)
Design of controlled flipping
RBS-mRFP(reverse)
hix RBS-tetA(C)hixpLac hix
![Page 83: Synthetic Biology Blends Math, Computer Science, and Biology A. Malcolm Campbell Reed College March 7, 2008](https://reader034.vdocuments.mx/reader034/viewer/2022051620/56649ef05503460f94c004d0/html5/thumbnails/83.jpg)