CDOs(Creative Designer Organisms)

in Biology

Natural selection

"Nothing in Biology Makes Sense Except in the Light of Evolution"

- a 1973 essay by the evolutionary biologist Theodosius Dobzhansky

Artificial selection – Directed evolution

10,000 ya present day

In plasmid pK214, Lactococcus K214 has, with the help of insertion-sequence elements, collected genetic information from four other species to construct an antibiotic survival kit that also works in E. faecalis. pK214 is a live record of previous genetic exchange between pathogenic and nonpathogenic bacteria in food-associated environments. It is further demonstration of the presence of transmissible antibiotic-resistance genes in the human food chain. The resistant bacteria probably originated from antibiotic treatment of the cows. As lactococci may be found together with enterococci and staphylococci as part of the cows microflora, resistance transfer and pick-up may have occurred in the animals or during cheesemaking, where enterococci, listeria and staphylococci survive and eventually multiply.

A plasmid with segments from many former bacterial hosts

Significant Scientific Milestones in Biotechnology

1663: 

Cells first described by Hooke.

1830:   Proteins are discovered.

1855:   Escherichia coli (E. coli) bacterium discovered (later becomes a major tool for biotechnology).

1940:   Avery demonstrates that DNA is the "transforming factor" and material of genes.

1953:   Double helix structure of DNA is first described by Watson and Crick.

1973:   Cohen and Boyer develop genetic engineering techniques to "cut and paste" DNA and reproduce the new DNA in bacteria.

1976:   The first working synthetic gene is developed.

1977:   Genentech scientists and their collaborators produce the first human protein (somatostatin) in a bacterium (E. coli).

1978:   Genentech scientists and their collaborators produce recombinant human insulin.

1979:   Genentech scientists produce recombinant human growth hormone.

1982:   Eli Lilly and Company markets Genentech-licensed recombinant human insulin - the first such product on the market.

1983:   Polymerase chain reaction (PCR) technique conceived (will become a major means of copying genes and gene fragments).

1985:   Genentech receives FDA approval for Protropin for growth hormone deficiency in children - the first biotech drug manufactured and marketed by a biotech company.

1990:   Human Genome Project (HGP), an international effort to map all the genes in the human body, is launched.

1994:   BRCA1, the first breast cancer susceptibility gene, is discovered.

1995:   The first full gene sequence of a living organism other than a virus, is completed for the bacterium Haemophilus influenzae.

2000:   First draft of human genome sequence completed by the HGP and Celera Genomics.

The GloFish is a trademarked brand of genetically modified (GM) fluorescent zebrafish with bright red, green, and orange fluorescent color. Although not originally developed for the ornamental fish trade, it is the first genetically modified animal to become publicly available as a pet

Golden Rice

Phenotypes of transgenic rice seeds. Bar, 1 cm. (A) Panel 1, untransformed control; panels 2 through 4, pB19hpc single transformants lines h11a (panel 2), h15b (panel 3), h6 (panel 4). (B) pZPsC/pZLcyH co-transformants lines z5 (panel 1), z11b (panel 2), z4a (panel 3), z18 (panel 4).

Turning carotene into gold. The carotenoid biosynthetic pathway of plants. Carotenoids are synthesized in the central isoprenoid pathway within plastids. All isoprenoids (more than 20,000 different compounds exist in plants) are built from the common precursor isopentenyl diphosphate (IPP). IPP is thought to be synthesized in plastids from pyruvate and glyceraldehyde-3-phosphate. The first committed step in the carotenoid pathway is the head-to-head condensation of two molecules of geranyl geranyl diphosphate (GGPP) to produce phytoene. Phytoene synthase is encoded by psy, phytoene desaturase by crtI, and lycopene -cyclase by lcy. Golden rice engineered to produce -carotene accumulates lutein and zeaxanthin as well.

phytoene synthase (psy) originating from daffodil (Narcissus pseudonarcissus)

bacterial phytoene desaturase (crtI) originating from Erwinia uredovora

Lycopene -cyclase from Narcissus pseudonarcissus

X. Ye et al., Science 287, 303 -305 (2000)

Structures of the T-DNA region of pB19hpc used in single transformations, and of pZPsC and pZLcyH used in co-transformations. Representative Southern blots of independent transgenic T0-plants are given below the respective Agrobacterium vectors. LB, left border; RB, right border; "!", polyadenylation signals; p, promoters; psy, phytoene

synthase; crtI, bacterial phytoene desaturase; lcy, lycopene -cyclase; tp, transit peptide.

Two major developments

Large scale DNA synthesis

Large scale DNA sequencing

Much of the work being done at Synthetic Genomics stems from a voyage made by the scientist J. Craig Venter (in green tank top) aboard his 95-foot sailing sloop, the Sorcerer II, outfitted as a seagoing lab. To his left is Tony Knap, senior research scientist at the Bermuda Biological Station for Research. The expedition set sail around the world in spring 2003.

The expedition's test voyage to the Sargasso Sea off Bermuda, an area thought to have low species diversity, turned up more than a million unexpected genes. Samples included at least 1,800 species of bacteria, including 100 new ones.

The Sorcerer II began its round-the-world trip in Nova Scotia (far right on the map), then headed west through the Panama Canal to Australia, then further west around South Africa.

Bring us your problem, and we will solve it

Synthetic Biology refers to a variety of experimental approaches that either seek to modify or mimic biological systems

One goal of Synthetic Biology is the engineering of biological systems to fulfill a particular purpose

Drubin et al. (2007) Designing Biological Systems. Genes and Development 21:242-254

http://www.syntheticbiology3.ethz.ch/

Paleome - a set of persistent genes that define the replicator and constructor programs

Biology

Top down to bottom up

From reductionism to synthesis

Drubin et al. (2007) Designing Biological Systems. Genes and Development 21:242-254