It's A Minimal Life

    Frankenstein Lite:

 It's Alive, more or less.

Tom Knight has always liked to build things from scratch.  I first knew him as one of MIT's Artificial Intelligence Laboratory's foremost firmware hackers,but he has  evolved into a founder of synthetic biology , the emerging discipline that addresses the debugging-- and embodiment--of genetic codes . “I gave it a name at least,” he told Nature at a  Swiss conference last week.

Unlike Systems Biology  or Artificial Life, Synthetic Biology is an engineer's game. Biologists have been building computer models for years , but Syn Bio's goal is to create  new and functional gene sequences, or edit old ones to reduce their encumbrance by  junk or random  DNA sequences that help parse  gene expression, but destabilize the storage and replication of 'useful'  information.  Just as byzantine Windows software doomed early PC's to terminal systems crashes , off-the-shelf DNA also leads to eventual  cellular complications, like death.

The  conference climaxed in a announcement awaited--and feared-- ever since Vitalism went infarct with the synthesis of  urea seven generations ago .  A dead ringer for life has at last been created in the lab.

Having sequenced the tiny genome of Mycoplasma genitalium, Venter Institute  molecular biologists assembled a copy of a vital part of that sequence from Certifiably Not Alive off-the-shelf synthetic amino acids. Stuck inside partially  eviscerated, and hence very dead,  Mycoplasma capsids, the  molecular assembly kick-started the nanocorpses' metabolism. The former cells are once again alive, and by the mycoplasmae's minimalist standards , frisky as the ceiling of the Sistine Chapel.

Unlike Systems Biology  or Artificial Life, Synthetic Biology is an engineer's game. Biologists have been building computer models for years , but Syn Bio's goal is to create  new and functional gene sequences, or edit old ones to reduce their encumbrance by  junk or random  DNA sequences that help parse  gene expression, but destabilize the storage and replication of 'useful'  information.  Just as byzantine Windows software doomed early PC's to terminal systems crashes , off-the-shelf DNA also leads to eventual  cellular complications, like death.

The  conference climaxed in a announcement awaited--and feared-- ever since Vitalism went infarct with the synthesis of  urea seven generations ago .  A dead ringer for life has at last been created in the lab.

Having sequenced the tiny genome of Mycoplasma genitalium, Venter Institute  molecular biologists assembled a copy of a vital part of that sequence from Certifiably Not Alive off-the-shelf synthetic amino acids. Stuck inside partially  eviscerated, and hence very dead,  Mycoplasma capsids, the  molecular assembly kick-started the nanocorpses' metabolism. The former cells are once again alive, and by the mycoplasmae's minimalist standards , frisky as the ceiling of the Sistine Chapel.

According to Nature's  Brendan Maher,

Classic biology is a matter of discovery and collecting of facts to put them in an understandable framework. Systems biology looks to model that framework in a way that allows predictions to be made. Synthetic biology looks to create the system anew.

For example, George Church of MIT,an editor of Molecular Systems Biology  , works on

"engineering all of the amber (UAG) stop codons out of E. coli to “free up the genetic code,” and make those codons available for other amino acids generally unused by E. coli. His team has made, he says, 25 mutations changing G to A in a single strain.... Church is also working on developing a mirror image of a polymerase to synthesize left handed DNA (no, not Z-DNA), and has been studying the co-evolution of bacterial strains engineered to rely on each other for specific metabolic processes...Church is also working on developing a mirror image of a polymerase to synthesize left handed DNA (no, not Z-DNA), and has been studying the co-evolution of bacterial strains engineered to rely on each other for specific metabolic processes.

For about the same reasons that  Ubergeeks pride themselves on spare elegance in  machine language programming, SynBio hackers would like to see if  minimal cells unencumbered by junk genes can outperform the wild and wooly ones produced by the random mutations of evolution.

This is naturally ,or un-naturally " a topic likely to raise temperatures among the metaphysically challenged members of the intelligent Design movement as well as  mundane biologists.

Maher notes that a group headed by Giovanni Murtas of the University of Rome already aspires

"to engineer liposomes with just the right mix of cellular components that they might become self sufficient and replicate. Having watched this field for some time, it’s clear that progress is slow. This bottom up approach is different from that at the J. Craig Venter Institute which has been trying to reduce the genome of a known organism Mycoplasma genitalium to its minimal needed parts."

What I personally  find fascinating is the prospect of  "expanded DNA"  in which extra benzene ring homologs of the familiar  A, C, T, G base pairs yield a double helix  2.4 Angstroms larger than with natural  amino acids , and  which has room for  fluorine substituted amino acids of extreme biological activity. It could also  allow incorporation of "oligodeoxyfluorosides" (ODFs),  deoxyribose-phosphate oligomers in which nucleobases are replaced by hydrocarbon and heterocyclic fluorophores.

This sort of thing is unlikely to evolve in nature if only because many of the alternative  molecules fluoresce. This is dandy for diagnostics, but  would mean wholesale , and probably catastrophic mutation by ordinary sunlight.  Artificial life based on such a brew would only be safe in a Transylvanian dungeon with the curtains drawn ,and  if anything like it has evolved elsewhere in the universe  it must involve  energy sources other than photosynthesis.

Comments

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"..would like to see if cells unencumbered by junk genes can outperform .. the random mutations of evolution.

Of course this is all assuming there is such a thing as a "junk gene". There is now cause for debate about that very topic. It will be curious to see how their work helps determine whether "junk genes" really exist.

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