From SOSwiki

Introduction to Synthetic Biology : Fall 2012

• BioE 423/523, CSE 486/586, EE 423/523
• Instructor: Prof. Eric Klavins
  • Office Hours: Tu, Th 8:30AM - 10:20AM, CSE 236
    • Office hours on 11/13 are 10am - noon.
• Teaching Assistant: Kevin Oishi
  • Office Hours: Mo, Fr, 10:00AM - 11:20AM, Sieg 128
• MWF 11:30-12:20

• Grading (Undergrads): Homework : 30%, Midterm : 30%, Final : 30%, Project : 10%
• Grading (Grads): Homework : 30%, Midterm : 25%, Final : 25%, Project : 10%, Review : 10%
• Homework policies: The lowest homework grade will be dropped. Extra credit will be recorded and used subjectively when determining letter grades. Homework must be turned in on time. Late homeworks are not accepted except for prearranged travel or unexpected illness.

Schedule

	Date	Topic	Readings and Other Materials	Assignment	Solution
1	9/24	History	A variety of optional readings are listed below.	A1, due 10/1	A1 Solution
	9/26	Synthetic Biology	Special Issue of Science on Synthetic Biology and optional overviews of synthetic biology.
	9/28	Gene Expression	Find a tutorial that speaks to you
2	10/1	Chemical Kinetics ODEs in Matlab	For more on chemical reactions, check out Lecture 2 of Feinberg's notes. The notation is a bit different, but the ideas are the same.	A2, due 10/8	A2 Solution
	10/3	Introduction to gro	Read the paper on gro. A few other papers are listed below.
	10/5	iGEM!	Check out UW's iGEM wiki page and also read about other teams.
3	10/8	Gene Regulation	Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems. Optional readings are listed below.	A3, due 10/15	A3 Solution
	10/10	Modeling Gene Regulation	Boolean networks
	10/12	Synthetic Gene Networks	A Robust and tunable gene oscillator
4	10/15	Signaling	Check out Bonnie Bassler's TED Talk on quorum sensing . 0.gro,1.gro,2.gro,3.gro. Optional readings are listed below.	A4, due 10/22	A4 Solution
	10/17	Pattern Formation	This paper demonstrates some of the impossibility ideas we discussed. More papers are listed below.
	10/19	Extra Pattern Formation Slides	le_example.gro,midpoint.gro
5	10/22	Noise	Stochastic Gene Expression. Other noise papers listed below.	A5, due 10/29	A5 Solution
	10/24	Modeling Noise	Nothing required, but you might want to check out the list below of books on probability.
	10/26	Noise in Gene Expression	You can read my 2009 course notes on stochasticity. Links to other resources are below.
6	10/29	Review
	10/31	MIDTERM
	11/1	Bioweapons, biosecurity, and ethics	Look at the PBS Documentary on the Living Weapon.
7	11/5	Midterm Results and Solutions
	11/7	Example of the moment equation method (no notes).	Other examples here.	A6, due 11/14	A6 Solution
	11/9	Computation	See my notes and also the paper by Soloveichik et al.
8	11/12	Vetrans Day
	11/14	Molecular Programming	Adleman's Paper. Qian and Winfree's Paper	A7, due 11/21
	11/16	Chemotaxis and Reaction/Diffusion
9	11/19
	11/21	Guest Lecture: Rob Carlson
	11/23	Thanksgiving
10	11/26	Guest Lecture: Georg Seelig
	11/28	Guest Lecture: James Carothers
	11/30	Olson Rao Amimeur Vines	Engineering microbial biofuel tolerance and export using efflux pumps Fundamental limits on the suppression of molecular fluctuations Ultrasensitivity and noise propagation in a synthetic transcriptional cascade EnvironmentallyControlled Invasion of Cancer Cells by Engineered Bacteria	A8, due 12/12
11	12/3	Rose Kooiman Bolten Younger	Designing synthetic regulatory networks capable of self-organizing cell polarization The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisiae Ribozyme-based insulator parts buffer synthetic circuits from genetic context A B Cell-Based Sensor for Rapid Identification of Pathogens
	12/5	Brettner Stevens Pfeuffer Parks	[asd asd] Modular Design of Artificial Tissue Homeostasis: Robust Control through Synthetic Cellular Heterogeneity Sequestration-based bistability enables tuning of the switching boundaries and design of a latch A design principle underlying the synchronization of oscillations in cellular systems
	12/7	FINAL
	12/12	FINAL MEETING : Simulation presentations!

Reading

1 History

• DNA Science, A First Course has a great history in it.
• Biology is Technology covers the economics of the coming biotechnological age.
• Carslon, The changing economics of DNA synthesis, Nature, 2009.

2 Synthetic Biology Overviews

• Special Issue of Science on Synthetic Biology: Read the introduction, news, reviews and perspectives sections.
• Five hard truths: http://www.nature.com/news/2010/100120/pdf/463288a.pdf
• Adventures in Synthetic Biology
• Andrianantoandro, Basu, Karig and Ron Weiss, Synthetic biology: new engineering rules for an emerging discipline. Molecular Systems Biology 2, 2006.
• Arkin and Fletcher, Fast, Cheap and Somewhat in Control. Genome Biology 7(8), 114, 2006.
• Basu, Karig and Weiss, Synthetic biology: new engineering rules for an emerging discipline. Molecular Systems Biology 2, 2006.
• Caleb J. Bashor, Andrew A. Horwitz, Sergio G. Peisajovich, and Wendell A. Lim, Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems. Annual Review of Biophysics 39, 515-537 (2010).
• Guillaume, Mutalik, and Arkin, Toward rational design of bacterial genomes. Current Opinion in Microbiology, 2011.

3 Biology Reviews

• A good text on biochemistry is essential. We like Lehninger Principles of Biochemistry, Fourth Edition, 2004.
• A Youtube video on transcription and translation.
• The Inner Life of the Cell
• Transcribe and translate a gene -- interactive! (somewhat misleading in the translation step, as the code seems not complimented like it should be).
• Lots of other online tutorials are available. Try googling "Gene Expression Tutorial". For example, this one.
• Raser and O'Shea, Noise in Gene Expression: Origins, Consequences, and Control, Science 2005.
• McAdams and Arkin. Stochastic mechanisms in gene expression, PNAS, 1997.

4 Chemical Kinetics

• Feinberg's Notes. Read the first two chapters.

5 gro

• S.S. Jang, K.T. Oishi, R.G. Egbert, and E. Klavins, Specification and simulation of multicelled behaviors, ACS Synthetic Biology, Vol. 1, No. 8, pp. 365--374. 2012.
• E.W. Dijkstra, Guarded Commands, Nondeterminacy and Formal Derivation of Programs, CACM, 1975.
• PRISM is a stochastic guarded command language like gro, except super formal and accompanied by a model-checker.

6 iGEM

• Last year's UW Team
• This year's UW Team

7 Gene Regulation

• Cox, Surrette, and Ellowitz describe engineered promoters.
• Isaacs, Swyer, and Collins discuss engineered riboregulators in RNA synthetic biology.
• Bayer and Smolke build riboregulators with RNA aptamers and ribozymes in Eukaryotes.

8 Gene Regulation

• A more recent paper on identifying gene networks based on expression patterns using boolean networks.

9 Synthetic Gene Networks

• A genetic toggle switch in E. coli
• rewritable digital storage in living cells
• transciptional oscillator in E. coli
• Another toggle switch/oscillator in E. coli
• A tunable oscillator in mammalian cells;
• Induced cellular differentiation.
• Yokobayashi, Weiss, and Arnold perform directed evolution on a genetic circuit
• Egbert and Klavins fine-tune genetic circuits using simple sequence repeats.
• Lou, Stanton, Chen, Munsky, and Voigt suggest a method for buffering synthetic circuits from genetic context.

10 Signaling

• Bonnie Bassler's TED Talk on quorum sensing .
• You, Cox, Weiss and Arnold, Programmed population control by cell–cell communication and regulated killing, Nature, 2004.
• Basu, Gerchman, Collins, Arnold and Weiss, A synthetic multicellular system for programmed pattern formation. Nature 434, 1130-1134, 2005.

11 Pattern Formation

• Howard Gutowitz, Cellular Automata, 1991.
• Stephen Wolfram, A New Kind of Science, 2002.
• Daniel Yamins, Radhika Nagpal, Automated Global-to-Local Programming in 1-D Spatial Multi-Agent Systems, AAMAS, 2008.

13 Noise

• Elowitz, Levine, Siggia, and Swain. Stochastic Gene Expression in a Single Cell, Science, 2006.
• Swain, Elowitz, Siggia. Intrinsic and Extrinsic Contributions to Stochasticity in Gene Expression, PNAS, 2002.
• Raj and van Oudenaarden, Single-molecule approaches to stochastic gene expression, Annual Review of Biophysics, 2009.
• Thattai and van Oudenaarden, Intrinsic noise in gene regulatory networks. PNAS, 2001.
• Lestas, Vinnecombe, and Paullson, Fundamental limits on the suppression of molecular fluctuations, Nature, 2010.

14 Modeling Noise

• Go look up all the definitions in today's lecture on Wikipedia or Planet Math.
• Feller, An Introduction to Probability Theory and its Applications. This is simply the best book out there on probability.
• Wilkinsen, Stochastic Modelling for Systems Biology. This is a good book for how probability is used in biology. Also covers the basic definitions.

15 Noise in Gene Expression

• Klavins, 2009 Course Notes on Stochasticity, 2009.
• Ozbudak, Thattai, Kurtser, Grossman and van Oudenaarden, Regulation of noise in the expression of a single gene, Nature Genetics 2002.

16 Ethics, Biosafety, Biowarfare

• American experience material on biowarfare: http://www.pbs.org/wgbh/americanexperience/features/timeline/weapon-timeline/
• Video on polio reconstruction: http://www.youtube.com/watch_popup?v=hfElVabRh2Y&vq=medium#t=31.
• The CDC's biosafety guidlines: http://www.cdc.gov/biosafety/publications/bmbl5/index.htm
• Presidential commission on synthetic biology: http://www.bioethics.gov/documents/synthetic-biology/PCSBI-Synthetic-Biology-Report-12.16.10.pdf

Links

• Library proxy information: http://www.lib.washington.edu/help/connect.html
• Last Year's Wiki
• Assignment Dropbox: https://catalyst.uw.edu/collectit/dropbox/koishi/23996
• Class GoPost: https://catalyst.uw.edu/gopost/board/koishi/30230/