20.20:Advanced topics

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Advanced Topics in Synthetic Biology: reading schedule

Discussions will be 1 hour long during Wednesday 2-5 studio block

TOPIC DATE Discussion leader(s) Discussion paper(s) Related paper(s) to enjoy
A Voyage To Lilliput:
How a small number of AA substitution change activity of a protein
Wed Feb 6 Natalie Kuldell and Drew Endy

Turning lambda Cro into a transcriptional activator.Bushman FD, Ptashne M.Cell. 1988 Jul 15;54(2):191-7.
PMID 2968842

DENK ppt here

Genetic Switch: Phage Lambda and Higher Organisms Mark Ptashnepreviewed here

or Sci Am summary (request from NK or DE)

Slide rule optional:
Computational design of novel protein activities
Wed Feb 13 Stephanie Nix and Matt Gethers

Computational design of receptor and sensor proteins with novel functions.Looger LL, Dwyer MA, Smith JJ, Hellinga HW.Nature. 2003 May 8;423(6936):185-90.
PMID 12736688

David Baker's protein folding game
NCBI protein viewer CN3D
Nature heart Legos™:
Proteins are modular too
Wed Feb 20 Kay Aull + Jessica Keenan

A eukaryotic transcriptional activator bearing the DNA specificity of a prokaryotic repressor. Brent R, Ptashne M.Cell. 1985 Dec;43(3 Pt 2):729-36.
PMID 3907859

Ptashne “Two ‘What if” experiments” PMID 15055587

Brent “Build Artificial” PMID 15055588

Better odds in Vegas:
DNA elements are modular too, allowing for circuits, but circuits don't always work
Wed Feb 27 Angi Wu and Robbie Barbero Combinatorial synthesis of genetic networks.Guet CC, Elowitz MB, Hsing W, Leibler S.Science. 2002 May 24;296(5572):1466-70.

PMID 12029133

Ultrasensitivity and noise propagation in a synthetic transcriptional cascade.Hooshangi S, Thiberge S, Weiss R.Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3581-6.

PMID 15738412

Darwin is alive and well:
Directed evolution at the device level
Wed Mar 5 Mike Lee and Stephen Payne Directed evolution of a genetic circuit.Yokobayashi Y, Weiss R, Arnold FH.Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16587-91.

PMID 12451174

NK and DE OoT
I demand the cone of silence:
nature's constraints on genetic circuit design
Wed Mar 12 Roshini Zachariah and another presenter Design of molecular control mechanisms and the demand for gene expression. Savageau MA.Proc Natl Acad Sci U S A. 1977 Dec;74(12):5647-51.

PMID 271992

Rules for biological regulation based on error minimization.Shinar G, Dekel E, Tlusty T, Alon U.Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):3999-4004.

PMID 16537475

Intelligent Design:
Functional composition at the device level
Wed Mar 19 Kate Broadbent and Mike Oh A modular and extensible RNA-based gene-regulatory platform for engineering cellular function.Win MN, Smolke CD.

Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14283-8.
PMID 17709748

Golden year: the gift of memoriesIgor Teper Nature 2006 July 27; 442: 484
doi 10.1038/442484a
Spring Break Mar 24-28 No class all week
Writing in genetic code:
DNA construction and editing technologies
Wed Apr 2 article 1:
Robbie Barbero
article 2:
Mike Lee
Article 1:
Single-step assembly of a gene and entire plasmid from large numbers of oligodeoxyribonucleotides.Stemmer WP, Crameri A, Ha KD, Brennan TM, Heyneker HL.

Gene. 1995 Oct 16;164(1):49-53.
PMID 7590320
Article 2:
Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. Gibson et al. Science. 2008 Jan 24; [Epub ahead of print]
PMID 18218864

Church automated genome editing paper, if available.
We're only human:
What is the state of the art?
Wed Apr 9 article 1:
Mike Oh
article 2:
Angi Wu
Article 1:
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
Takahashi K, Yamanaka S.Cell. 2006 Aug 25;126(4):663-76.
PMID 18035408
Article 2:
Environmentally controlled invasion of cancer cells by engineered bacteria.

Anderson JC, Clarke EJ, Arkin AP, Voigt CA.J Mol Biol. 2006 Jan 27;355(4):619-27.
PMID 16330045

remember to point out that the tumor destroying bacteria do not have epigenetic memory, and perhaps raise the question as to why / how the ES cells do...
Little Red Corvette:
Once you've got the DNA, where do you put it? Introducing... THE CHASSIS
Wed Apr 16 article 1:
Matt Gethers
article 2:
Sophia Roosth
Article 1:
A vesicle bioreactor as a step toward an artificial cell assembly.Noireaux V, Libchaber A.Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17669-74.
PMID 15591347
Article 2:

Emergent properties of reduced-genome Escherichia coli.Pósfai G, Plunkett G 3rd, Fehér T, Frisch D, Keil GM, Umenhoffer K, Kolisnychenko V, Stahl B, Sharma SS, de Arruda M, Burland V, Harcum SW, Blattner FR. Science. 2006 May 19;312(5776):1044-6.
PMID 16645050

Can we understand it? Can we program it?
Apr 23 article 1:
Stephanie Nix
article 2:
Kate Broadbent
Article 1:
Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements.Dewannieux M, Harper F, Richaud A, Letzelter C, Ribet D, Pierron G, Heidmann T. Genome Res. 2006 Dec;16(12):1548-56.

PMID 17077319
Article 2:
Hsp90 as a capacitor for morphological evolution. Rutherford SL, Lindquist S.Nature. 1998 Nov 26;396(6709):336-42.
PMID 9845070

Darwin’s Surprise: Why are evolutionary biologists bringing back extinct deadly viruses? Michael Specter New Yorker article
2020: Empire of Reason Wed Apr 30 article 1:
Stephen Payne
article 2:
Roshini Zachariah
Article 1:
1970 Matt Meselson paper on three pronged approach against bioweapons
maybe PMID 5440151 or PMID 5263755
Article 2:One commentary or piece of fiction... something forward looking, optimistic, The Golden Years
Freshmen Team Presentations (Wed Apr 30,)
Wed May 7,
May 14

Grades for 20.902/20.947

All assignments should be dropped into the homework drop-box, found here

Part 1: Readings

  • Paper 1 (15%): presented with a partner
  • Paper 2 (20%): presented solo
  • Response journal (15%): your thoughts about the papers you don't present. Instructions for this assignment are here

Presentation requirements are here

Part 2: Team Mentoring

  • Progress reports (25%): 2x one page summary of your freshman team's work, due Wednesday March 12th, and Wednesday April 9th
  • Mentoring journal (10%): 2x one page summary of your freshman team's dynamics, due Wednesday March 12th, and Wednesday April 9th
  • Team's project average (10%): based on the grade for the 3 major assignments submitted by your freshman team
  • Instructor Leverage (5%): discretionary adjustment by NK and DE