Category: Research

The cover story of the 10 January 2002 issue of Nature describes work in the advancing field of proteonmics, the cataloging and functional analysis of the suite of proteins that operate inside an organismís cells. The subject of the report is a pioneering study describing the first draft of a functional map of the yeast proteome. The map visualizes an entire network of protein complexes and their interactions in yeast Saccharomyces cerevisae, forming a basis for the operative organization underlying a cellís activity under different conditions.

The map, developed by a team of scientists from the biotechnology start-up company CellZome and the European Molecular Biology Laboratory (EMBL), is the first of its kind. The map characterizes the function and interactions of 1,440 yeast proteins comprising 232 multi-protein assemblies, or complexes, which directly affect biological activity.

Interestingly, the EMBL press release describes the work as a large-scale study of the ìmolecular machinesî formed by nearly two thousand proteins in a living cell, including the discovery of over a hundred new protein machines, ranging in size from two to eighty-three molecules (The EMBL press release is also available as a nicely-illustrated 5-page Acrobat PDF document). The Cellzome AG press release emphasizes the work as a major step towards transforming information from genome projects into applications such as the discovery of new drugs.

Yet another perspective is available in an article on the Nature Science Update website ("Proteome reveals promiscuity", by Helen Pearson, 10 January 2002).

An interesting item on the Lawrence Berkeley National Laboratory site ("A New Clue to How Viruses Infect Cells", by Lynn Yarris, 16 November 2001) covers research into powerful viral molecular motors done by Carlos Bustamante and his coworkers in the Berkeley Lab's Physical Biosciences Division.

The research was previously covered here on Nanodot on 22 October 2001. A technical paper by Bustamante and coworkers (" The Physics of Molecular Motors ") is available online as an Adobe Acrobat PDF file.

According to a press release (3 January 2002), researchers at the University of Illinois at Urbana-Champaign and the University of Pennsylvania have discovered that carbon nanotubes packed with fullerene spheres, like so many peas in a pod, have tunable electronic properties. They reported their work in the 3 January 2002 issue of Science.

"Our measurements show that encapsulation of molecules can dramatically modify the electronic properties of single-wall nanotubes," said Ali Yazdani, a professor of physics at UI. "We also show that an ordered array of encapsulated molecules can be used to engineer electron motion inside nanotubes in a predictable way."

To explore the properties of these novel nanostructures, Yazdani and coworkers used a low-temperature scanning tunneling microscope to image the physical structure of individual peapods and to map the motion of electrons inside them. The encapsulated fullerenes modify the electronic properties of the nanotube without affecting its atomic structure. "In contrast to unfilled nanotubes, peapods exhibit additional electronic features that are strongly dependent on the location along the tube," Yazdani said. Because the local electronic properties of single-wall nanotubes can be selectively modified by the encapsulation of a single molecule, the technique might one day be used to define on-tube electronic devices.

Update: An article on the Wired website ("Nanotech Fine-Tuning", by Mark K. Anderson, 4 January 2002) provides some additional coverage, with some perspective from Yazdani, as well as Cees Dekker and Calvin Quate.

from the A-new-twist dept.
According to a press release (2 January 2002), Nadrian Seeman and his co-workers at New York University have been able to create a more robust, controllable version of the rudimentary DNA-based device that Seemanís group first reported they had created in January 1999 (see report in Foresight Update 36).
According to the release, the new device "improves upon previously developed nano-scale DNA devices because it allows for better-controlled movement within larger DNA constructs. The researchers say that the new device may help build the foundation for the development of sophisticated machines at a molecular scale, ultimately evolving to the development of nano-robots that might some day build new molecules, computer circuits or fight infectious diseases." Their research is reported in the 3 January 2002 issue of Nature.

The January 1999 version of the device constructed from DNA molecules had two rigid arms that could be rotated from fixed positions by adding a chemical to the solution. However, the chemical affected all molecules within a structure uniformly. The most recent findings demonstrate how movement can be manipulated within molecule pairs without affecting others within a larger structure. This is done by inserting DNA ìsetî and ìfuelî strands into individual molecule pairs. Scientists used special DNA molecule pairs and produced a half-turn rotation by converting them from one configuration into a second configuration by removing the set strands with fuel strands and replacing them with new set strands that reconfigure the structure of the device.

Update: An illustration of the new DNA-based device, along with a not particularly lucid explanation of the change in configuration that produces the rotation, is available on this page of the Seeman groupís website.

Dr. Seeman was awarded the 1995 Feynman Prize in Nanotechnology (see Foresight Update 23) in recognition of his pioneering work to synthesize complex three-dimensional structures with DNA molecules.

from the The-worm-turns dept.
According to a press release (10 December 2001), two University of Colorado at Boulder researchers working with GenoPlex Inc. in Denver have identified a biological switch that controls lifespan in tiny worms, a finding that could have applications for mammals, including people.
The switch, known as DAF-16, is a protein that can either lengthen or shorten the lifespan in the eyelash-sized roundworm, C. elegans, said CU-Boulder psychology Professor Thomas Johnson. Johnson, who is a fellow in the universityís Institute for Behavioral Genetics, or IBG, said DAF-16 is a critical part of a complex signaling pathway that involves insulin and glucose. Henderson has identified a molecule that embodies a trade off, said Johnson. "If DAF-16 is ëon,í it triggers less reproduction, more efficient cell repair and longer lives. On the other hand, if DAF-16 is ëoff,í the result is more reproduction, worse cell repair and a shortened lifespan," he said.
There is a good possibility scientists could develop a pharmaceutical intervention that would trigger translocation of DAF-16 into the cell nucleus of a variety of animals, including humans, said Henderson. This would cause organisms to lower their reproduction level and fight off the negative impacts of free radicals.

According to a press release (18 December 2001), a team of researchers led biophysicist Bing Jap led a team from Lawrence Berkeley National Laboratory's Life Sciences Division have determined the structure and function of a cell membrane protein, called aquaporin 1 (AQP1), that is specific for water molecules. The structure reveals the how the AQP1 can transport water through the cell membrane at a high rate while effectively blocking everything else that is larger or smaller, even individual protons, the nuclei of hydrogen atoms.

Each AQP1 channel is made up of four identical subunits, each with an entrance chamber on the outside of the cell envelope, connected to a similar chambeer inside the cell by a long, narrow pore. "The secret of AQP1's specificity is two-fold: it selects for size and for chemical nature," Jap says. "There is a very narrow constriction in the pore, which admits no molecule bigger than water. To keep out molecules smaller than water there is also a chemical filter, formed by the specific orientation and distribution of the amino acid residues lining the pore."

Molecules attempting to enter the channel are bound to water molecules that are stripped away in the pore; charged species are therefore left with net electrical charge. "The filter strongly rejects charged molecules or ions, even as small as single protons," Jap explains. The unique distribution of amino acid residues along the pore wall also accounts for the channel's ability to move water quickly. The channelís internal environment has both hydrophilic and hydrophobic components. Water molecules readily get in because of the hydrophilic sites, but the hydrophobic regions prevent them from binding too frequently. Thus water and only water flows freely in and out of the cell through AQP1's pores, the direction of flow depending only on changing relative pressure inside and outside the cell.

Similar work on the structure and workings of an ion-channel protein sorter for potassium ions was reported here on 2 November 2001.