Foresight Update 6
page 4
A publication of the Foresight Institute
 Recent
Progress: Steps Toward Nanotechnology
by Russell Mills
Big projects
The Research Development Corporation of Japan is soliciting
resumes from chemists and solid state physicists interested in
researching the "architecture and function of
self-assembling organic systems--their molecular design and
synthesis, the introduction of function, and the creation of
three-dimensional architecture." The 4-year effort is called
the Kunitake Molecular Architecture Project, and is part of ERATO
(Exploratory Research for Advanced Technology), sponsored by the
Japanese Government. [Ad in Chem. & Eng. News:
18Jan88, p65]
Plans for the genome mapping project are coming into focus. The
Program Advisory Committee on the Human Genome, formed by the
National Institutes of Health to lead the project, has adopted a
general strategy for the effort:
- The project will initially emphasize other complex
genomes, such as E. coli, yeast, nematode, fruit
fly, mouse, and a plant.
- Development of tools and technology for rapid sequencing
will be given preference over such particular
applications as studying genes responsible for genetic
diseases.
- The construction of new research facilities will be
considered part of the project.
- The safeguarding of genetic privacy will receive
significant attention.
[Science 243:167-168, 13Jan89]
|
Webmaster's Note: An
abstract of the Kunitake Molecular Architecture Project,
which ended in 1992, is available at:
A few of the many sources of information about The Human
Genome Project available on the WWW:
|
|
Microtechnology
Iwao Fujimasa at Tokyo University's Research Center for
Advanced Science and Technology says his group is developing a
robot small enough to travel inside the human body cutting and
treating diseased parts in veins and organs. The goal is a
machine less than .06 cm in size. [Wisconsin State Journal:
16Feb89]
Protein engineering
Proteins that have evolved by traditional means are not noted
for their stability. They tend to unfold and become inactive when
put into altered environments (like those likely to be
encountered in commercial applications). But redesigning
traditional proteins to make them more stable is feasible; a
research group led by B. W.
Matthews at the University of Oregon has provided a good
example. Reasoning that helical segments of a protein chain might
be stabilized by charged amino acids that interact with the
dipole field of the helix itself, the group constructed several
altered versions of the protein lysozyme from the phage
T4 (which attacks the E. coli bacterium). Lysozyme, an
enzyme that breaks up the cell wall of E. coli bacteria,
contains 11 helical segments. The researchers used maps of the
protein to select two of these helices for experimentation. They
made three different lysozymes by substituting aspartic acid for
an amino acid near an end of one or both of these helices.
Measurements made on the resulting proteins revealed an increase
in activity of 160% to 430%, and an increase in melting
temperature of up to 4 degrees C. Since helical components are
found in most active proteins, this method may be widely used to
make proteins more resistant to temperature and other
environmental conditions. [Nature 336:651-656,
15Dec88]
Other work done on T4 lysozyme by Matthews' group was aimed at
incorporating a molecular "on-off switch" into the
enzyme. In its native form, lysozyme has an open pit (or
"active site") into which its substrate fits while
being acted upon. The researchers designed a switch consisting of
two thiol (-SH) groups. Under suitable chemical conditions,
thiols can form covalent bridges with each other (-SS-); other
conditions break the bridges (-SH HS-). A pair of thiols was
built into lysozyme by replacing two amino acids on opposite
sides of the enzyme's active site by cysteine--an amino acid with
a thiol-containing side-chain. By changing the composition of the
solution containing the experimental lysozyme, the researchers
could cause the cysteines to form a bridge across the active
site, completely inactivating the enzyme. The process was
completely reversible. [Science 243:792-794,
10Feb89]
Biologists in Britain have successfully changed the preferred
substrate of a bacterial enzyme. Lactate dehydrogenase (LDH)
normally catalyzes the interconversion of pyruvate and lactate in
the metabolism of sugars. Another enzyme, malate dehydrogenase
(MDH) catalyzes an analogous interconversion of oxaloacetate and
malate. Though structurally related, the amino acid sequences of
the two enzymes are about 80% different. By making appropriate
substitutions for 3 amino acids, the researchers turned LDH into
a better catalyst for oxaloacetate/malate conversion than MDH
itself. [Science 242:1541-1544, 16Dec88]
Many bacteria (including E. coli) propel themselves
through water by rotating a helical filament called a flagellum.
Flagella are driven at a few cycles per second by motors about 20
nanometers in diameter anchored in the bacterial membrane; power
comes from a current of protons. Each motor is made of about 20
different polypeptides. Mutations in the genes for two of these
proteins (MotA and MotB) result in bacteria with paralyzed
flagella. When normal genes are then introduced into these
bacteria, the paralysis is reversed--a turnover of MotA and MotB
components in the flagellar motors seems to be a regular
bacterial routine. At Harvard University videotapes have shown
that the reversal of paralysis occurs as a series of 8 equal
increases in torque. They conclude from this that there are eight
torque generators in each flagellar motor.
Electron microscope images show rings of up to 16 particles in
bacterial membranes of bacteria that produce MotA and MotB
proteins. It therefore seems that a torque generator consists of
two particles in which MotA and MotB occur.
The amino acid sequences of MotA and MotB proteins have led
researchers to speculate that MotA contains a channel for
conducting protons through the bacterial membrane, while MotB
connects the torque-generating machinery to the membrane. [Science
242:1678-1681, 23Dec88]
|
Webmaster's Note: Pictures
of the bacterial flagellar motor are available at:
|
|
Microscopy
As is well known, the scanning tunneling microscope (STM) can
make images of conducting materials (metals, semiconductors) at
atomic resolution. It has proved capable of imaging molecules of
non-conducting materials, as well--a fact that has been difficult
to explain, since the STM operates by passing an electron current
between an electrode and the sample.
Researchers at IBM, Xerox, and Stanford University have now
proposed a mechanism for this phenomenon. In the absence of a
sample, a biasing voltage between an STM electrode and a graphite
substrate allows a current to pass between electrode and
substrate, overcoming an energy barrier in the process. But when
a sample is adsorbed to the substrate, the size of the barrier is
altered in the vicinity of the sample, thereby changing the rate
of electron flow when the electrode passes over this region. The
generality of this explanation suggests a much greater range of
application for the STM than was originally thought. Researchers
will be gleefully scanning all manner of materials for years to
come. [Nature 338:137-139, 9Mar89]
A group at Berkeley, California has used an STM to study
double-stranded DNA deposited onto graphite. The DNA was examined
dry--in air rather than in solution--and was not given the
conductive coating once thought to be necessary for electron
tunneling to occur. The resolution achieved appeared to be finer
than 1 nm; helical structure was clearly visible, as well as
bumps that might correspond to individual DNA bases. [Science
243:370-372, 20Jan89]
[Suprisingly little is said in print about possible future use of
STM images in the automated reading of genetic or amino-acid
sequences.--RM]
Reliability and Performance
The reduction of thermal noise will likely be a major
preoccupation of those who design nanomachines. The random
jiggling of atoms in the components of such machines will reduce
the accuracy of their intended motions, in some instances leading
to lower performance or outright errors. These thermal motions
can be reduced by cooling, but traditional methods of
refrigeration become awkward and expensive when very low
temperatures are needed.
Sophisticated cooling methods are now being suggested for
microelectronic circuits, based on a concept called
"stochastic cooling." In electronics applications, this
would involve the detection of random current fluctuations and
their cancellation by feedback. Electron temperatures under 10-6
K are in principle reachable by a stochastic refrigerator. [Nature
337:597-598, 16Feb89]
[The basic notion of stochastic cooling may be relevant to the
problem of how to suppress the non-electronic thermal noise in
nanomachinery, such as that which would interfere with the
positioning of atoms by an assembler arm.--RM]
Dr. Mills has a degree in Biophysics and assists in the
production of Update.
From Foresight Update 6, originally
published 1 August 1989.
Foresight thanks Dave Kilbridge for converting Update 6 to
html for this web page.
|