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:
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]
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:
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]
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.
