delightfully self-referential

James Watson's genome sequenced
Discoverer of the double helix blazes trail for personal genomics.

Erika Check
Nobel laureate James D. Watson peered deep into his genome yesterday. And soon, anyone else interested in his genetic makeup will be able to do the same.

Scientists in Houston presented Watson with a DVD of his genome sequence, which they said was the "first individual genome to be sequenced for less than $1 million". The carefully worded claim may be an acknowledgement that another personal genome project has already been completed: J. Craig Venter has deposited his genome sequence into the public GenBank database, he told Nature two weeks ago.

Such personal genomes are for now largely symbolic, because it's difficult to draw concrete information about a person's health from his or her genome sequence.

And genetic self-knowledge does not necessarily help a person: the only deliberate omission from Watson's sequence is that of a gene linked to Alzheimer's disease, which Watson, who is now 79, asked not to know about because it is incurable and claimed one of his grandmothers.

Scientists said yesterday that Watson's genes showed some predisposition to cancer. Watson — who, working with Francis Crick, deduced DNA's structure in 1953 — has had skin cancer, and a sister had breast cancer, he said yesterday. But it's unlikely that reading Watson's genome would have allowed doctors to predict what type of cancer he might have suffered before it was diagnosed.

Price cut

That could change in the near future, when hundreds or thousands of individual genomes are sequenced and scientists learn to correlate the sequence with health outcomes.

The US National Human Genome Research Institute is planning to sequence hundreds of individual genomes, and the private Archon X Prize in Genomics has announced a $10 million cash reward for the first team to sequence 100 genomes in 10 days.

Sequencing technology is still too expensive for most people — and some geneticists are concerned that sequencing prominent scientists makes genomics look like a gimmick for the rich and powerful (see 'Celebrity genomes alarm researchers').

But the price is dropping quickly. The Human Genome Project, which was declared complete four years ago, cost $3 billion over 13 years. Sequencing Watson's genome took two months.

The Human Genome Project, which Watson helped initiate in 1988, assembled a composite 'reference' genome of DNA from many individuals, in contrast to the sequence given to Watson yesterday.

Watson's genome is expected to be described in a scientific publication soon, and was submitted to the GenBank yesterday. The project was initiated by scientists at the sequencing technology company 454 Life Sciences in Branford, Connecticut, and at Baylor College of Medicine in Houston, Texas.

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Math and Motion

Circles, slaloms, figure eights, and loop-the-loops – biologists studying the motion of Listeria monocytogenes sensed that these paths were related, but they didn’t have a good way to define what fit in and what didn’t. A remarkably simple new mathematical description, published online in the Proceedings of the National Academy of Sciences, reproduces all these shapes with just one pair of equations and only two key variables. Besides helping to identify bacterial mutants, the equations suggest which mechanisms could be driving the motion.

Last winter, Vivek Shenoy, an associate professor of engineering at Brown University, was matched with Julie Theriot, an associate professor at the Stanford School of Medicine, at a biophysics "boot camp" run by Rob Phillips at the California Institute of Technology. Theriot studies Listeria, a disease-causing bacterium that hijacks the actin network of an infected cell to propel itself. Embedded in a network of actin fibers, the bacterium keeps adding actin molecules at its back end, pushing itself forward and leaving behind an actin tail tracing its path.

Those paths intrigued Shenoy as soon as he saw Theriot’s movies of Listeria traveling in the two-dimensional world of a microscope slide. Some bacteria spun in circles, others followed a sine curve, some followed a path like the cloverleaf exchange on a highway. The circles, he thought, were easy to explain. If an actin filament pushed just a bit off center, the bacterium would go in circles, like a swimmer who paddles harder on one side.

With a bit more thought, he cracked the sine curve. What if that off-center point rotated around the axis of motion" When it pushed harder on the right, the bacterium would move to the left; when it pushed to the left of center, the cell would move to the right. If the bacterium moved forward faster than it curved around, a swerving pattern would result.
The clincher came as Shenoy worked out the mathematics to describe this kind of motion. The exact same equation, it turned out, also described the figure-eights, cloverleaves and other looping patterns they had observed. In fact, nearly every time they recorded a new pattern, they found it fit the equation. An equation that can predict observations clearly has a lot going for it, but a mathematical description is not the same thing as a biological mechanism.

"If we can understand things is a simpler setting, such as this one," said Shenoy, "then we can use those insights to study more complex phenomena."
As the team works to fully explain the motion they observe, Shenoy’s equations can narrow the possibilities, ruling out mechanisms that cannot generate both the circular and the spinning component of the motion.
With just two variables – an offset distance and an angle relative to the forward motion – they could reproduce every track they saw, except those produced by mutant microbes that Theriot introduced. The mutants stood out as different. They produced a skidding kind of pattern instead of the graceful curves that most of the bacteria traced.

"The human visual cortex is really good at seeing patterns," said Theriot, "but this gives us a quantitative framework for asking questions that before we could only ask qualitatively."
Being able to pinpoint just how different the mutants are is valuable, said Theriot, because they often are less infectious than normal Listeria. Once Listeria invades a host cell, it uses the actin mechanism to move from cell to cell, never again exposing itself to the organism’s extracellular immune system. A microbe with a deficient movement mechanism is a microbe with less ability to invade neighboring cells.

Link: Abstract

Source: Brown University

Quantum secrets of photosynthesis

Through photosynthesis, green plants and cyanobacteria are able to transfer sunlight energy to molecular reaction centers for conversion into chemical energy with nearly 100-percent efficiency. Speed is the key - the transfer of the solar energy takes place almost instantaneously so little energy is wasted as heat. How photosynthesis achieves this near instantaneous energy transfer is a long-standing mystery that may have finally been solved.
A study led by researchers with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) at Berkeley reports that the answer lies in quantum mechanical effects. Results of the study are presented in the April 12, 2007 issue of the journal Nature.

"We have obtained the first direct evidence that remarkably long-lived wavelike electronic quantum coherence plays an important part in energy transfer processes during photosynthesis," said Graham Fleming, the principal investigator for the study. “This wavelike characteristic can explain the extreme efficiency of the energy transfer because it enables the system to simultaneously sample all the potential energy pathways and choose the most efficient one.

Fleming is the Deputy Director of Berkeley Lab, a professor of chemistry at UC Berkeley, and an internationally acclaimed leader in spectroscopic studies of the photosynthetic process. In a paper entitled, Evidence for wavelike energy transfer through quantum coherence in photosynthetic systems, he and his collaborators report the detection of “quantum beating” signals, coherent electronic oscillations in both donor and acceptor molecules, generated by light-induced energy excitations, like the ripples formed when stones are tossed into a pond.

Electronic spectroscopy measurements made on a femtosecond (millionths of a billionth of a second) time-scale showed these oscillations meeting and interfering constructively, forming wavelike motions of energy (superposition states) that can explore all potential energy pathways simultaneously and reversibly, meaning they can retreat from wrong pathways with no penalty. This finding contradicts the classical description of the photosynthetic energy transfer process as one in which excitation energy hops from light-capturing pigment molecules to reaction center molecules step-by-step down the molecular energy ladder.

"The classical hopping description of the energy transfer process is both inadequate and inaccurate," said Fleming. "It gives the wrong picture of how the process actually works, and misses a crucial aspect of the reason for the wonderful efficiency."

Co-authoring the Nature paper with Fleming were Gregory Engel, who was first author, Tessa Calhoun, Elizabeth Read, Tae-Kyu Ahn, Tomas Mancal and Yuan-Chung Cheng, all of whom held joint appointments with Berkeley Lab’s Physical Biosciences Division and the UC Berkeley Chemistry Department at the time of the study, plus Robert Blankenship, from the Washington University in St. Louis.

The photosynthetic technique for transferring energy from one molecular system to another should make any short-list of Mother Nature’s spectacular accomplishments. If we can learn enough to emulate this process, we might be able to create artificial versions of photosynthesis that would help us effectively tap into the sun as a clean, efficient, sustainable and carbon-neutral source of energy.

Towards this end, Fleming and his research group have developed a technique called two-dimensional electronic spectroscopy that enables them to follow the flow of light-induced excitation energy through molecular complexes with femtosecond temporal resolution. The technique involves sequentially flashing a sample with femtosecond pulses of light from three laser beams. A fourth beam is used as a local oscillator to amplify and detect the resulting spectroscopic signals as the excitation energy from the laser lights is transferred from one molecule to the next. (The excitation energy changes the way each molecule absorbs and emits light.)

Fleming has compared 2-D electronic spectroscopy to the technique used in the early super-heterodyne radios, where an incoming high frequency radio signal was converted by an oscillator to a lower frequency for more controllable amplification and better reception. In the case of 2-D electronic spectroscopy, scientists can track the transfer of energy between molecules that are coupled (connected) through their electronic and vibrational states in any photoactive system, macromolecular assembly or nanostructure.Read on...

Fleming and his group first described 2-D electronic spectroscopy in a 2005 Nature paper, when they used the technique to observe electronic couplings in the Fenna-Matthews-Olson (FMO) photosynthetic light-harvesting protein, a molecular complex in green sulphur bacteria.

Said Engel, "The 2005 paper was the first biological application of this technique, now we have used 2-D electronic spectroscopy to discover a new phenomenon in photosynthetic systems. While the possibility that photosynthetic energy transfer might involve quantum oscillations was first suggested more than 70 years ago, the wavelike motion of excitation energy had never been observed until now."

As in the 2005 paper, the FMO protein was again the target. FMO is considered a model system for studying photosynthetic energy transfer because it consists of only seven pigment molecules and its chemistry has been well characterized.

"To observe the quantum beats, 2-D spectra were taken at 33 population times, ranging from 0 to 660 femtoseconds," said Engel. "In these spectra, the lowest-energy exciton (a bound electron-hole pair formed when an incoming photon boosts an electron out of the valence energy band into the conduction band) gives rise to a diagonal peak near 825 nanometers that clearly oscillates. The associated cross-peak amplitude also appears to oscillate. Surprisingly, this quantum beating lasted the entire 660 femtoseconds."

Engel said the duration of the quantum beating signals was unexpected because the general scientific assumption had been that the electronic coherences responsible for such oscillations are rapidly destroyed.

"For this reason, the transfer of electronic coherence between excitons during relaxation has usually been ignored," Engel said. "By demonstrating that the energy transfer process does involve electronic coherence and that this coherence is much stronger than we would ever have expected, we have shown that the process can be much more efficient than the classical view could explain. However, we still don’t know to what degree photosynthesis benefits from these quantum effects."

Engel said one of the next steps for the Fleming group in this line of research will be to look at the effects of temperature changes on the photosynthetic energy transfer process. The results for this latest paper in Nature were obtained from FMO complexes kept at 77 Kelvin. The group will also be looking at broader bandwidths of energy using different colors of light pulses to map out everything that is going on, not just energy transfer. Ultimately, the idea is to gain a much better understanding how Nature not only transfers energy from one molecular system to another, but is also able to convert it into useful forms.

"Nature has had about 2.7 billion years to perfect photosynthesis, so there are huge lessons that remain for us to learn,” Engel said. “The results we’re reporting in this latest paper, however, at least give us a new way to think about the design of future artificial photosynthesis systems."

Source: Lawrence Berkeley National Laboratory