Ribosomes: nanotech ver. 1.0

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william...@gmail.com

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Jul 9, 2004, 2:01:03 AM7/9/04
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Ribosomes are fascinating and fundamental to life as we know it. They
are possibly the most ancient remaining relics from the previous era
of life, the RNA world. And as the only functioning examples of
nano-scale programmable molecular assemblers, ribosomes are on the
cutting edge of a nanotech future. This group has been created for
discussion of all things related to ribosomes.

In the olden times of the Internet (more than a decade ago), Usenet was
a valuable medium for discussion of a variety of scientific subjects,
among other things. In the recent past, use of Usenet has declined
into obscurity and spam. This is unfortunate. Perhaps these new
Google groups can revive this valuable medium for communication between
people on specific topics such as ribosomes.

William

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slipp

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Dec 2, 2004, 12:03:41 AM12/2/04
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can you recommend some material to read on this -- i have picked up
molecular biology of the cell -- is that a good place to start?

in particular, i would like to better understand the `previous era of
life' -- is this generally accepted. in my reading, it is characterized
as a strong hypothesis without much further discussion.

this is just such a astonishing realm of knowledge i had no idea of and
am trying to pick it up as i can while working professional.

perhaps since there is very little activity in this group at the
moment, you could just post an item or two -- for example,

a. in mboc, the dual nature of RNA -- that it can both encode and act
in lieu of a protein -- is cited as making it a likely candidate for
your preverious era of life -- could you expand on that?

b. i am not sure i understand the current explanation of how
replication is thought to have emerged from non-reproducing molecules?

c. just take a particular aspect of ribosome and expand on it ...
since i am a lay person, and depend on all my learning from buying
texts and just studying myself and thinking about it, i never get a
sense of the people in this field, or how they think, or the greater
expertise ... so, if you were to write something i would greatly
appreciate and ask many questions ... until the threads pick up.
thanks.

stan

Karan Kampani

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Dec 2, 2004, 4:03:40 AM12/2/04
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Hi,
I am a new member of the group.Am equally interested in the past and
future of ribosome.Am a Biomedical Engineer and am enrolled in Masters
program.Plz let me know in what terms could nanotechnology be
important to ribosomes?And what is the state of research in this field

Karan

William Knight

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Dec 3, 2004, 5:37:45 PM12/3/04
to ribo...@googlegroups.com
> can you recommend some material to read on this -- i have picked up
> molecular biology of the cell -- is that a good place to start?
>
I haven't seen a recent edition of MBOC, but I would say that it is a
good introduction to the field. Personally, that book was one of the
things which led me to leave computer programming and pursue a degree
in biochemistry (although I have tried to combine these two fields).

> in particular, i would like to better understand the `previous era of
> life' -- is this generally accepted. in my reading, it is characterized
> as a strong hypothesis without much further discussion.
>
I believe that we do have some evidence, beyond pure hypothesis, about
the prior existence of the RNA world, though I would grant that such
evidence may be disputable. One example of such evidence is the
Ribosome itself, in which the most important functional components are
RNA, not protein. In addition, there are modern experimental
demonstrations of RNA-based replication. A nice review of recent work
is Joyce, 2004, Annu. Rev. Biochem, "Directed Evolution of Nucleic
Acid Enzymes". Again, however, the existing experimental data is
incomplete. We do not currently have a complete detailed theory for
the origin of self-replicating RNA systems.

> this is just such a astonishing realm of knowledge i had no idea of and
> am trying to pick it up as i can while working professional.
>
> perhaps since there is very little activity in this group at the
> moment, you could just post an item or two -- for example,
>
> a. in mboc, the dual nature of RNA -- that it can both encode and act
> in lieu of a protein -- is cited as making it a likely candidate for
> your preverious era of life -- could you expand on that?
>
RNA is both a genetic molecule and a functional molecule. The genetic
part refers to encoding of information. Its structure allows it to be
unfolded so that its linear sequence can be copied. It shares this
genetic property with DNA.

The 'acting in lieu of a protein' is the functional aspect. This
refers to the three-dimensional structure of the molecule, which can
enable certain RNA molecules to catalyze chemical reactions, such as
ligation and cleavage. This catalytic capability is what it shares
with proteins, although the catalytic capabilities of RNA are
generally much more limited than those of proteins.

The reason that RNA is a better candidate for an earlier era of life
than the current system is that a self-replicating RNA system could
more easily come into existence than our existing DNA-protein-based
system of self-replication. A modern DNA-protein-based system
consists of more complex and specialized components. I believe that
it is much more difficult to imagine an evolutionary sequence
involving these specialized DNA-Protein components than one involving
only RNA components.

By an evolutionary sequence, I mean a sequence that begins from
non-replicating conditions and simpler molecules, and arrives at the
current complex specialized system. For example, what would be a
simpler, strictly-protein-and-DNA-based version of sequence-specific
amino-acid ligation than the current ribosome? It is possible to
imagine such simpler mechanisms, but I believe that it is much easier
to imagine simpler RNA-based mechanisms.

> b. i am not sure i understand the current explanation of how
> replication is thought to have emerged from non-reproducing molecules?
>
A simple outline of some of the arguments might be as follows:

Things begin with a collection of pre-existing building blocks that
are individual residues. These residues spontaneously link together to
form small oligomers of random sequence. A subset of these random
oligomers possess incrementally-increased catalytic capability
relative to others in the set. A subset of this catalytic subset will
catalyze particular ligation reactions so that the population of the
subset itself is increased, relative to the general population. This
is referred to as an auto-catalytic metabolic network. Once you have
limited replication of the network, then cycles of variation and
selection can increase the rate and specificity of the replication,
resulting in systems of longer, sequence-specific molecules that are
capable of reproducing themselves.

Stuart Kauffman has written some good books about the origins of
autocatalytic metabolic networks. One such book is "The Origins of
Order".

> c. just take a particular aspect of ribosome and expand on it ...
> since i am a lay person, and depend on all my learning from buying
> texts and just studying myself and thinking about it, i never get a
> sense of the people in this field, or how they think, or the greater
> expertise ... so, if you were to write something i would greatly
> appreciate and ask many questions ... until the threads pick up.
> thanks.
>
> stan
>
>
One particular and exciting aspect about ribosomes is the recent
emergence of atomic resolution 3D crystal structures, available at
http://www.rcsb.org/pdb. Example PDB model codes of ribosomal
subunits include 1FKA and 1FFK. You can download these models and
view them with freely available open-source software such as Rasmol,
PyMOL or Ribosome Builder (a program that I am developing). Ribosome
Builder is available at http://rbuilder.sourceforge.net.

William Knight

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Dec 3, 2004, 6:21:22 PM12/3/04
to ribo...@googlegroups.com
> Hi,
> I am a new member of the group.Am equally interested in the past and
> future of ribosome.Am a Biomedical Engineer and am enrolled in Masters
> program.Plz let me know in what terms could nanotechnology be
> important to ribosomes?And what is the state of research in this field
>
> Karan
>
>
Ribosomes are a kind of nanotechnology because they allow the
programmable assembly of molecular components. They are less
general-purpose than Drexlerian diamondoid nano-assemblers, because
ribosomes only assemble amino-acids into a linear chain. However,
ribosomes have the considerable advantage of actually existing in the
real world, as opposed to being purely theoretical, which is the
current state of Drexlerian nano-assemblers.

Currently, people are able to produce systems of ribosomes in-vitro
that are capable of limited production of proteins and short peptides,
although such systems are mostly used to learn how the process of
protein translation itself works. In addition, it is possible to add
specific genes to bacterial species and then grow them in culture, so
that the bacterial ribosomes will produce large, industrial quantities
of the proteins that are coded by these inserted genes.

I envision at some point the creation of ribosome-based systems to
produce proteins where the specific sequence fed to the ribosomes is
done in a way that is more direct than gene-insertion and
transcription. I haven't worked out the details, but the idea would
be to input some kind of electronic signal that would be transduced
somehow and specify the next codon in a sequence that is read by the
ribosome. A kind of 'electronic mRNA'. Such a system would make the
ribosomal machinery a much more powerful version of nanotechnology.

In addition, the tRNA molecules could be modified to include a larger
variety of residues to be assembed than the current small set of 20
amino acids. This has already been done, to a limited extent, but I
expect it would become much more useful in self-replicating in-vitro
systems of ribosomes that are under electronic control.

Scoove

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Dec 3, 2004, 9:14:59 PM12/3/04
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Hi,
I am a new member of the Ribosomes group. I am equelly fasanated by
the study of Ribosomes. I am studing to become a geneticist and
thought I would have an esier time passing tests if I fully understood
the Ribosomes topic. That is why I joined. My question is, how far
has science progressed in this area?

William Knight

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Dec 4, 2004, 12:19:52 AM12/4/04
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Research in the structure and function of ribosomes has been ongoing
for more than 40 years, since their existence was first postulated in
the late 1950's. For a readable review of the early history you might
want to check out the book "The Eighth Day of Creation: Makers of the
Revolution in Biology" by Horace Judson.

However, only in the last few years, starting in August of 2000, have
we received full atomic resolution crystal structures of the ribosome.
These structures are an extraordinary achievement and a major
milestone towards understanding how the ribosome works.

These structures represent 'snapshots' of the ribosome in various
states. The next stage in ribosome research is to understand the
dynamics of ribosome movement, and all of the individual sub-steps of
the translational cycle. The next decade promises to be an exciting
one, where a flood of experimental data is combined with increasingly
powerful and sophisticated computer hardware and software to process
this data.

The creation of detailed atomic models and simulations of the ribosome
and other complex macromolecular systems within the cell will lay the
foundations for a comprehensive understanding of single cell and
intercellular activity. I believe this is the next logical step to
follow upon the success of decoding the Human genome and other
genomes.

kmac

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Dec 15, 2004, 8:59:35 AM12/15/04
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Hello:
I'm also a lay person who finds this fascinating. I just wanted to
thank the members that have been posting explanations for taking the
time to do so. I want to let you know that it is appreciated.
Kevin

Lil B

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Feb 9, 2005, 11:13:52 PM2/9/05
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William is right Scoove. It is remarkable the way science has
progressed in the area of ribosomes, specfically Biological
Conciderations In The Approach to Medicine. For example, genetic
disorders or the genetic aspect of human disease.

A little over-third of the protiens (genes) in each human exsit in a
form that differs from the one present in the majority of the
population. This degree of genetic variability (polymorphism) among
normal people accounts for many natural occuring variations in body
traits e.g. intelligence, height, and blood pressure. Moreover, these
same variations handle every environmental challenge, including those
that produce disease. Thus, it is concidered that every human disease
occurs as a result of someones genetic makeup and his environment.
However though, in certain disease the genetic component is so
overwhelming that it communicates in a predictable manner without a
requirement for extraordinary environmental challenges.

Imagine having a special ring. A wedding ring that your grandfather
gave to your grandmother years ago when they were married. Because of
the value of that ring, your dad gave the same ring to your mother. And
now that you are a big boy enough to tie the knot, that will even be
the ring that you will give you wife. Important to you or not, this
genetic ring is being handed down troughout the family. In this case,
the ribosome would be whatever reason your grandfather chose to buy
that ring instead of another. For this purpose, let's say that he
bought it because it was cheap.

Ribosomes are associated with the mRNA after it leaves the cell nucleus
located in the cytoplasm. From there it serves as a template for the
synthesis of ribosomal proteins. So, your dad would be the mRNA after
he leaves the house (cell nucles) and enter into the real world
(cytoplasm) where he becomes associated with his own set of
circumstances (ribosomes). These circumstances (ribosomes) contribute
to the financial hardship (synthesis)your father was experiencing
thereby serving as a template (budget) for how much he can spend
(synthisis). And because he spent less money, your family would have to
posses a cheap ring. Some common genetic disorders are and their
specfic ethnic groups of increased frequency: Cystic fibrosis -North
Europeans, Adult lactase deficiency -Chinese, and some kinda, Glucose
6-phosphate deficiency -African Blacks.

Hope this helps. Holla back!

william...@gmail.com

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Feb 10, 2005, 3:37:44 PM2/10/05
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That is an interesting analogy, Lil B. Not quite sure if I completely
follow it, but it is more colorful than the usual analogy of the
ribosome. In that analogy, the ribosome can be compared to a machine
shop that reads a blueprint (RNA) which is a copy of the original draft
document (DNA). The ribosome then 'reads' this blueprint to produce
the useful parts and tools (proteins) of the factory (cell).

Your observation about genetic variability is certainly cause for great
excitement and continued research in biology. Because each of us
possesses a unique collection of genetic traits, a number of people
have predicted the coming era of 'personal genomics'. This era, which
hopefully will happen soon, relies upon advances in sequencing
technology so that each of us can possess the precise sequence of part
or all of our own genome, which can than serve as a valuable resource
for preventitive and thereapeutic medicine.

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