tisdag 22 mars 2011

Life is science’s new focus?

On discovering Life.

Dimitar Sasselov is the Bulgarian director of the Origins of Life Initiative at Harvard University. It studies everything from planet formation and detection to the origin and early evolution of life, and the research forms a natural bridge between the physical and the life sciences. Focuses on radiation and matter interference.

Yet as these cosmic-scale projects, LHC and NASAs Kepler mission, open the second decade of the new millennium they are returning science to a frontier that seems oddly 19th century. Science is going back to the scale of life—that middle ground of minute energies and high complexities between the immense galaxies and infinitesimal particles. Two separate quests, one to discover habitable worlds, the other to synthesize artificial organisms, now unite to redefine “life” and its place in the universe.

There is an aspect of life sciences that has been largely absent: the confrontation of fundamental questions of biology much as particle accelerators grapple with fundamental questions of physics. The roll call of early pioneers and prospectors is notable, but short. Fortunately, increasing numbers of researchers are now re-entering this fertile frontier.

The open secret of this emerging frontier is that we do not have a fundamental definition or understanding of life. Similarly, we do not understand life’s origins, how life emerges from chemistry. We do know that the chemistry of life on Earth, or “Terran” biochemistry for short, is rather restrictive in its molecular permutations. Unnecessarily so, it seems, given the enormous choice of good options provided by chemistry for building biological bodies and functions. However, we do not know whether nature or nurture is the reason. The bio-chemistry we see (and are!) could be universal, like gravity, where the same basic rules apply anywhere. Or our biochemistry could instead be one of many options, one that just happened to fit Earth’s environmental conditions. /quote.

Alternative biochemistries is needed, says the article. Words, words...

Two simultaneous but distinct approaches have defined the work on the origins and biochemical diversity of life. One approach is from within, "RNA-first", following paths that begin with existing Terran biochemistry and move away from its set of molecules and networks in search for alternatives. The other approach is from outside, "Metabolism-first", following paths from plausible prebiotic initial conditions. Both have scored recent breakthroughs.

John D. Sutherland’s lab here (University of Manchester), in a brilliant example of systems chemistry, has performed a synthesis of nucleotides—building blocks like DNA and RNA — in which two of a nucleotide’s crucial parts, the base and the sugar, emerge as a single unit under natural conditions. RNA-world hypothesis.
RNA is for life: The origin of life on Earth required — at some point — the synthesis of a genetic polymer from simple chemicals. The leading candidate for this role is RNA, but although 'activated' ribonucleotide molecules (the building blocks of RNA) can polymerize without enzymes, no plausible route had been found by which the ribonucleotides could have formed. Now a team from the University of Manchester has found such a route. They also show that a widely held assumption about ribonucleotide synthesis — that the molecules formed from pre-existing sugar molecules and RNA bases — isn't necessary for RNA to have formed on prebiotic Earth.
Did life begin with RNA? An RNA polymer is a string of ribonucleotides, each made up of three distinct parts: a ribose sugar, a phosphate group and a base — either cytosine or uracil, known as pyrimidines, or the purines guanine or adenine. Origins of Life: "A new way of looking at the synthesis of RNA sidesteps a thorny problem in the field." The traditional view is that the ribose sugar and nucleobase components of ribonucleotides formed separately, and then combined. But no plausible reactions have been found in which the two components could have joined together. Powner et al. show that a single 2-aminooxazole intermediate could have contributed atoms to both the sugar and nucleobase portions of pyrimidine ribonucleotides, so that components did not have to form separately.

Powner, M. W., Gerland, B. & Sutherland, J. D. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239-242 2009.

" Although inorganic phosphate is only incorporated into the nucleotides at a late stage of the sequence, its presence from the start is essential as it controls three reactions in the earlier stages by acting as a general acid/base catalyst, a nucleophilic catalyst, a pH buffer and a chemical buffer. For prebiotic reaction sequences, our results highlight the importance of working with mixed chemical systems in which reactants for a particular reaction step can also control other steps."

Moving in the opposite direction, George Church’s lab at Harvard has achieved the successful synthesis of functioning ribosomes — the molecular machines that read genetic code and make the proteins for cells. Synthetic biology - and the Personal Genome Project, a new era of individualized medicine, in which drug treatments and other therapies can be optimized by custom - matching them with a person's unique genetic makeup. He helped initiate the Human Genome Project in 1984. Engineering Life: Building a FAB for Biology

Today scientists have learned how to write genetic code, and as described by J. Craig Venter, such state-of-the-art biotechnology work is “creating software that makes its own hardware.” Venter said this in 2008 when reporting his team’s successful artificial transformation of one bacterium species into another. The synthesis of ribosomes of your choice is a big deal, because, to borrow computer jargon, it allows you to change the “operating system” when writing new genetic code. The next major step beyond modifying Terran organisms is to create alternative biochemistries and entirely new trees of life. And these new trees are supposed to help us with the energy question. Both Church and Venter are linked to bio-fuelcompanies.

One example of an alternative biochemistry that is both intuitive and relatively close to fruition is the case of “mirror” life — that is, life with biochemistry essentially identical to our own, but composed of molecules of the opposite chirality, or “handedness.” Terran biochemistry is based exclusively on proteins built from “left-handed” amino acids; for balance, all Terran sugars are right-handed. Scientists understand why organisms can’t be chirally ambidextrous, with equal parts left- and right-handed proteins, but nobody knows whether the left-versus-right choice is a matter of chance or necessity.

This is the most essential difference to ordinary matter, though. Why is chirality so important for Life?

And boundaries...
Cells were not primary, but a result of the function. Maybe the immunological question also is essential.

Mirror life will not lead to an artificial life form without the necessary next step of “compartmentalization” - any self-sustaining biochemistry needs a container to hold it. On Earth, cells are the containers — their semi-permeable membranes encapsulate all the biochemical machinery life needs. Jack Szostak’s lab at Harvard has shown how these membranes can naturally form to create “protocells” and how these protocells can even spontaneously reproduce by splitting into two and more protocells. Szostak’s constructs seem tantalizingly close to real cells.

Speed and change...
The other essential compound is emergence of proteins. They are often catalysts, speeding up the reaction. Thomas Cech 1986, findings that explain RNA's function as an enzyme in addition to being an informational molecule. Biological catalysis by RNA, 1986. He suggests 2004 that the RNA serves a very different function, providing a flexible tether for the protein subunits. Telomerase can switch between inhibition, shelterin and extension, he writes in coll. 2007 and 2006,The RNA world: the nature of modern RNA suggests a prebiotic RNA world a link between RNA and proteines. Remember, prebiotic reducing atmosphere whose principal components where CH4 and/or CO2 (carbons), NH3, and H2O. Could the so-called hot carbon-nitrogen-oxygen cycle function also on Earth, but slowly? Is the burning process what we call Life? Fractal inflation, says Chris King.
Traditional chemistry, despite its quantum foundations, treats molecules as arbitrary building blocks. This view is incorrect when non-linearity and dynamical feedback are taken into account. The origin of life is dependent on dynamical processes of free interaction, not forced reactions and involves fundamental interactive quantum bifurcations and feedback effects characteristic of non-linear dynamical systems. Major features of metabolism, including the role of nucleotides and polypeptides, light-absorbing chromophores, phosphate dehydration energy, RNA, the major features of the genetic code, Fe-S groups, ion and electron transport, phosphorylation and the citric acid cycle are all described as being generic features of a cosmically general bifurcation tree. * The rich diversity of structure in molecular systems is made possible by the profound asymmetries developing at the cosmic origin, between the nuclear forces, gravity and electromagnetism. Chemical bonding is a consequence of the non-linear inverse square law of electromagnetic charge interaction in space-time.
' + topologically quantized classical fields in TGD. DNA nucleotides are stable only inside regions containing ordered or liquid crystal water forming a macroscopic quantum phase. The ‘protein folding problem’, being genetically coded, in potential energy environment (entropy) with potentially quantum computation by the molecular orbitals form fractal structures both in the geometry of their primary, secondary, tertiary and quaternary structures and their active dynamics, as illustrated by the fractal dynamics of myoglobin and ion channels.

Radoslav Bozov has detected a "Carbon Signaling System". "Theory of Carbon Signaling. Negentropy vs Entropy - Emergence of Self Propagated Biological Systems" in the Book "Recent Researches in Modern Medicine", ISI,SCI Web if Science and Web of Knowledge, Cambridge, UK, 2011, pp. 98-114; ISBN: 978-960-474-278-3 here.
He wrotes me, when I ask for a comment:
The emergence of carbon signaling systems requires self propagated mechanism linking mutational forces as a function of asymmetric dicarboxilic acid oxidation and glycine/pyruvate amino transferring systems. Proteins only lower activation energy of transitional intermediates of interacting substrates without changing the form of initial interfering matter. Thus speeding up reactions. Simply Cyanide is a substrate not used by biological systems. It is a toxic compound used for gold refining. What happened back then was a very slow reaction that took much time until protein emerged. It is likely that transcription factor proteins emerged first as carbon transferring systems prior to membrane formation and compartmentalization of space.
Proteins are powerful catalysts partly because, as well having active foci, which can invoke effects such as quantum tunnelling, enzymes bring to bear a global coherence of action, arising from cooperative weak bonding, which makes for both very powerful and responsive active sites. The resonances.

Polymerization/dehydration is linked to lipids (carbon-chains) but polymers are not stable in an aqueous environment. Polymerization in modern cells is basically a process involving metabolic control, and it seems that the metabolic control must have been present from the beginning in some primitive form (homeostasis?).

Mutations and constraints.
Gerald Joyce at the Scripps Research Institute together with Tracey Lincoln made paired RNA catalysts, each of which could assemble the other when supplied with the right building blocks. Then the scientists mixed the paired molecules with RNA building blocks in test tubes. Because the RNA 'enzymes' were not perfect, and made different forms of each other, the original pairs mutated into new, 'recombinant' forms that out-competed the originals. The 'winning' enzymes changed depending on the conditions in the reaction mixture, such as the concentration of various RNA building blocks. Joyce's group had already made enzymes capable of catalyzing their own replication, but they could only reproduce themselves a limited number of times. The new enzymes can reproduce themselves indefinitely. "This is the first time outside of biology where you have immortalized molecular information," says Joyce. 'Hypercycles' — networks of enzymes that replicate each other — could give rise to self-sustaining populations of early life forms.
Lincoln, T. A. & Joyce, G. F. Science 10.1126/science.1167856 2009 (2008).

What is Life?
We can forget the famous criteries of Life, as replication. Virus is commonly seen as living today.
The Steven Benner group: 2011: Setting the Stage: The History, Chemistry, and Geobiology behind RNA RNA Worlds: From Life's Origins to Diversity in Gene Regulation. "A definition- theory for Life is needed to develope hypotheses relating to the "RNA-first" model. Paleogenetics, prebiotic chemistry, exploration independent of TerrianLife, and synthetic biology. We are missing something in our models of Reality?

I would say the quantum biology is missing. The essence of mind-matter? Or evolution itself? The non-linearity of charge interaction which causes chemical bonding also gives rise to further residual interactions at lower energies which are resolved by cooperative weak bonding.

While Venter is using a top–down approach — trying to 'boot up' a cell with an entirely synthesized genome — Joyce and Szostak take a bottom–up strategy by attempting to recreate the events that could have led to the existence of genes, cells and life as it is now. The next major step would be to create a system that doesn't just do the same thing over and over, but can evolve the ability to perform new tasks. The evolution.

Szostak won Nobel in medicine 2009 on telomerases, co-winners and collaborators, Elizabeth H. Blackburn and Carol W. Greider. Life on Earth, SciAm 9, 2009.

Other models...
There are also other RNA-models, many-sheeted spacetime in TGD, the evolution of life in intra-terrestrial environement, and models where life came from space, Robert Shapiro; Small molecule interaction..., "metabolism first". A Simpler Origin for Life, SciAm, 2007. Shapiro's suggested readings and here.

The Origin of Life, according to A. G. Cairns-Smith started with chrystals and clay minerals. Chemistry and the Missing Era of Evolution, 2008, Chemistry. 2008;14(13):3830-9.
Stuart Kauffman belongs to the same team with random networks exhibiting a kind of self-organization that he terms "order for free". Self-organization and selection must be combined (The Third Culture, 1995). Ceaseless creativity, God is the creativity yielding a global ethics of respect for all life. Beyond Reductionism - Reinventing The Sacred. Some works here.

"Metabolism first" approach, where self-reproducing and evolving proto-metabolic networks are assumed to have predated self-replicating genes, has met chritism here.

Peptide Nucleic acid first is the third variant invented 1991 by Nielsen (the various purine and pyrimidine bases are linked to the backbone by methylene carbonyl bonds), Stanley L. Miller, 1997: Peptide nucleic acids and prebiotic chemistry. Peter Nielsen, 2008.: A New Molecule of Life? Sci Am,Vol. 299, No.6, pages 64-71. Miller is famous for the nucleotide creation exp 1953, the Miller-Urey experiment. A New Game of Life, PNAs and protocells.

Panspermia is the fourth way (Crick).

Intelligent Design is a belief to fight Darwinian evolution only. I am not convinced Darwinian evolution is everything, there are more to social life and evolution, but I don't think Intelligent Design is the answer. We need to find the constraining rules.
Stephen Meyer, “Signature in the Cell,” overview - Meyer brings his discussion about the feasibility of RNA’s role as the early storehouse for cellular information to a conclusion, he recalls a twenty year old conversation with a philosophy professor about origin-of-life-research: “The field is becoming increasingly populated by cranks. Everyone knows everybody else’s theory doesn’t work, but no one is willing to admit it about his own.” Following this statement, Meyer fast-forwards into the present, and writes of his own assessment of the field twenty years later: “I found no reason to amend these assessments.” The work Meyer had been discussing that led up to that final dismissive statement was that of Gerald Joyce and Jack Szostak. - Intelligent Design is just noisy?

T. Cavalier-Smith is also a big name in evolution of Life. 1991:
The three major classes of intron are clearly of unequal antiquity. Structured (often self-splicing and sometimes mobile) introns are the most ancient, probably dating (at least for group I) from the ancestral (eubacterial) cell 3500 million years ago, and were originally restricted to tRNA. Protein-spliced introns (usually in tRNA) probably evolved from them by a radical change in splicing mechanism in the common ancestor of eukaryotes and archaebacteria, perhaps only about 1700 million years ago. Spliceosomal introns probably evolved from group-II-like self-splicing introns after the origin of the nucleus between 1700 and 1000 million years ago, and were probably mostly inserted into previously unsplit protein-coding genes after the origin of mitochondria 1000 million years ago.
Exploring Life's Origins. Multimedia project at the Museum of Science.

More than ever, over the uncarved terrain of the new biology, Venter and Church are blurring the distinction between the academic and the commercial. Selling Life? George Church, with more than a dozen graduate students and 18 postdoctoral researchers, runs one of the biggest labs in the richest university in the world. Next to Venter's institute, though, his still feels like a scrappy outfit in the corner. Joyce is dean of the faculty at one of our nation’s most prestigious research organizations.

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