Designing and building a minimal genome
A goal in biology is to understand the molecular and biological function of every gene in a cell. One way to approach this is to build a minimal genome that includes only the genes essential for life.
In 2010, a 1079-kb genome based on the genome of Mycoplasma mycoides (JCV-syn1.0) was chemically synthesized and supported cell growth when transplanted into cytoplasm.
Hutchison III et al. used a design, build, and test cycle to reduce this genome to 531 kb (473 genes). The resulting JCV-syn3.0 retains genes involved in key processes such as transcription and translation, but also contains 149 genes of unknown function.
Highlights
• An entire organism is modeled in terms of its molecular components
• Complex phenotypes can be modeled by integrating cell processes into a single model
• Unobserved cellular behaviors are predicted by model of M. genitalium
• New biological processes and parameters are predicted by model of M. genitalium
Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology that computational approaches are poised to tackle. We report a whole-cell computational model of the life cycle of the human pathogen Mycoplasma genitalium that includes all of its molecular components and their interactions. An integrative approach to modeling that combines diverse mathematics enabled the simultaneous inclusion of fundamentally different cellular processes and experimental measurements. Our whole-cell model accounts for all annotated gene functions and was validated against a broad range of data. The model provides insights into many previously unobserved cellular behaviors, including in vivo rates of protein-DNA association and an inverse relationship between the durations of DNA replication initiation and replication. In addition, experimental analysis directed by model predictions identified previously undetected kinetic parameters and biological functions. We conclude that comprehensive whole-cell models can be used to facilitate biological discovery.
Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871–base pair designer eukaryotic chromosome, synIII, which is based on the 316,617–base pair native Saccharomyces cerevisiae chromosome III.
Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling.
SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII.
The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.
Probabilities exceedingly low. But if not tried, probabilities = 0
SETI
Novel by Karl Sagan
Jodie Foster uses headsets to hear for signals (fantasy)
habitability vs. habited: concepts frequently confused by the media
Origin of Matter: we know about it
Origin of life: ?
before: “Life is so complex, that it would never happen again”
19:13 Vital Dust (book):
“Life is a cosmic imperative”
19:45 a switch in sentiment NOT based on any science
We don’t know how life came to exist, therefore we can’t estimate the odds.
20:25 Hypothesis of the cosmic imperative. How can we test it?
22:30 If we find life on Mars, probably it came from Earth.
26:15 shadow biosphere
28:30 Traditional SETI: very anthropocentric
?galactic beacon
32:00 Terrestrial engineering. Astroengineering.
35:30 Fermi paradox
37:35 Earth could have been visited along 4.5 billion years
38:24 Alien footprints … 100 million years old
1. Buried nuclear waste
2. Buried quarries or mines on Earth, or surface mining traces on moon, asteroids, etc.
3. Biotechnology
A bacterium that can grow by using arsenic instead of phosphorus.
F. Wolfe-Simon, J. Switzer Blum, T.R. Kulp, G.W. Gordon, S.E. Hoeft, J. Pett-Ridge, J.F. Stolz, S.M. Webb, P.K. Weber, P.C.W. Davies, A.D. Anbar and R.S. Oremland
Science. (2011). 332: 1163-1166. http://www.sciencemag.org/content/332/6034/1163.abstract http://felisawolfesimon.com
To hype, or not to(o) hype: Communication of science is often tarnished by sensationalization, for which both scientists and the media are responsible
EMBO Rep. 1 April 2012: 303-307. http://embor.embopress.org/cgi/reprint/13/4/303
Imagine a world where a computer tells you what to do and when—without having to log into your PC.
The Wall Street Journal talks with Google Executive Chairman Eric Schmidt on the technology of tomorrow.
synthetic biology — genetic engineering taken to a whole new level.
His most successful project to date: Jay Keasling and his team inserted or tweaked a dozen genes in yeast cells and turned them into tiny factories that churn out a partially synthetic version of artemisinin, a key drug in the leading treatment of malaria. (The usual source of artemisinin is a tree known as sweet wormwood, and there are not enough to meet the global demand.)
And now Amyris, one of the companies Keasling founded, “has a factory in Brazil that’s using the engineered yeast, taking in sugar and spitting out a product that’s a diesel fuel,” Keasling says. Already, that diesel is in buses in Rio and Sao Paulo.
There is, of course, a catch: “This diesel is still more expensive than petroleum-based diesel by quite a long shot.”
Craig Venter and team make a historic announcement: they’ve created the first fully functioning, reproducing cell controlled by synthetic DNA. He explains how they did it and why the achievement marks the beginning of a new era for science.
In 2001, Craig Venter made headlines for sequencing the human genome. In 2003, he started mapping the ocean’s biodiversity. And now he’s created the first synthetic lifeforms — microorganisms that can produce alternative fuels.
landmark paper: Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome
Science 2 July 2010: Vol. 329 no. 5987 pp. 52-56 http://www.sciencemag.org/content/329/5987/52
Design and synthesis of a minimal bacterial genome
A Whole-Cell Computational Model Predicts Phenotype from Genotype
Total Synthesis of a Functional Designer Eukaryotic Chromosome
Tired of Thinking? Google Says We Won’t Have To
Put Down Oil Drill, Pick Up The Test Tube: Making Fuel From Yeast 
franzcalvo 