In the search for new and better materials, many a scientist has turned to the study of living organisms. Generally these studies have focused on such tissues as bone or shell – complex mixtures of minerals, proteins and sugars that result in hard, strong, fracture-resistant materials. Recent research in the Institute's Structural Biology Department has shown that bones and shells share similar formation processes.

Bone and shell are composite materials in which the mineral component forms within a framework of soft macromolecules such as proteins. The framework is essentially a "mold" that directs the mineral formation. Bone grows continuously, layer by layer; but, unlike shell, it also undergoes constant remodeling. This makes it hard for scientists studying bone to distinguish new material from old, much less to trace the process by which bone is formed. Because of this difficulty, conflicting theories have arisen as to the mechanisms of bone formation. Many scientists thought that the minerals precipitate directly from a solution in the way that stalactites and stalagmites grow from elements dissolved in water. But findings published in the 1960s already hinted at the possibility that a different process was at work.

Ten years ago, research in a group headed by Profs. Lia Addadi and Stephen Weiner of the Institute's Structural Biology Department confirmed these earlier observations for shells. They showed that organisms first produce packets of amorphous material (unorganized material, as opposed to the ordered organization of crystal). These packets are transferred from the inside of cells to the building site – the spot where the mineralized tissue eventually forms. There, the packets undergo structural changes that turn them into a hard crystal. This observation triggered widespread interest in amorphous precursor mineral phases, and many different invertebrate mineralization processes were investigated.

Addadi and Weiner revealed this process in sea urchin spines, and their findings have been joined by a body of global research confirming that this method of construction is common to many different invertebrates that have shells, spines or other hard body structures. Addadi: "The original idea of precipitation from solution would require huge quantities of liquid to flow from inside the mollusk to the outside of its body. Transferring the materials in solid form – 'bricks and cement' – is a much more energy-efficient way of doing things."

While the issue has been more or less settled for the shells of invertebrates, the question of how vertebrate bones are formed remained unresolved. This is partly because of the difficulty inherent in attempting to observe a substance with no fixed location that exists for only a fleeting stage of growth. Recently, however, research student Julia Mahamid, together with Addadi and Weiner, found a biological system that enabled them to follow bone formation step by step and identify the processes taking place at each stage. This system is the fin of a small aquarium denizen called a zebrafish. The zebrafish fin bones, which continue to grow throughout the fish's lifetime, form a sort of fan. Each bony rib of the fan is composed of segments, and the segments nearest the fin's edge are always the newest. Thus the segments can be studied as a sort of timeline of bone formation. In addition, zebrafish, which live in relatively cold water, grow slowly, and the leisurely pace of their bone development enabled the scientists to get a good look at each stage.

Using both light microscopy and scanning electron microscopy, the scientists succeeded in observing abundant spherical parcels of amorphous mineral material in the newly formed fin bone. Their findings, which appeared in the Proceedings of the National Academy of Sciences (PNAS), USA, showed that about half the mineral makeup of the newer bone segments is amorphous – a fraction that dwindles in the segments farther away from the fin edge. Their observations suggest that the amorphous material does, indeed, turn to crystal over time.

These findings are shedding light on a number of scientific mysteries, giving scientists a unique perspective on how the hard substances in our body – bones and teeth – are formed. The scientists hope that a deeper understanding of these biological processes may, in the future, help researchers find cures for diseases involving faulty bone development or repair.

Prof. Lia Addadi's research is supported by the Clore Center for Biological Physics; the Ilse Katz Institute for Material Sciences and Magnetic Resonance Research; the Helen and Martin Kimmel Center for Nanoscale Science; the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly; and the Carolito Stiftung. Prof. Lia Addadi is the incumbent of the Dorothy and Patrick Gorman Professorial Chair.

Prof. Stephen Weiner's research is supported by the Kekst Family Center for Medical Genetics; the Helen and Martin Kimmel Center for Archaeological Science; the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly; and George Schwartzman, Sarasota, FL. Prof. Weiner is the incumbent of the Dr. Walter and Dr. Trude Borchardt Professorial Chair in Structural Biology.

Tomorrow's computer might be a quantum one based on the physics of particles smaller than atoms. No one is quite sure what a quantum computer should look like, or even whether it's possible to build a functional one; but scientists at the Weizmann Institute have been working on some of the basic questions that will need to be answered before we can begin to create this new kind of computer.

Is it a qubit?

At the level of atomic and subatomic particles, things work very differently from the macro world of everyday objects. For instance, there's wave-particle duality: The basic bits of matter and light behave sometimes as discrete particles and sometimes as waves, which can be in many locations at once. And there's quantum superposition – particles existing simultaneously in more than one state at a time – which could, theoretically, provide a dramatic increase in computing power. An electronic computer bit can be in only one of two states (0 or 1), whereas a quantum bit (called a qubit) can exist simultaneously in both 0 and 1, in an infinite number of different superpositions. The challenge for scientists is to connect these fragile quantum states to the larger world without destroying them.

Several years ago, Prof. Adi Stern of the Condensed Matter Physics Department came up with a way to test a system to see whether it could be used as a special kind of qubit – a topological quantum bit. The system in question involves, on the one hand, electrons moving in a very cold two-dimensional plane, with a strong magnetic field applied at right angles to the plane and, on the other, quasiparticles. These "imaginary" particles – which have electrical charges of one-third, one-quarter or one-fifth of an electron – don't exist in nature, but they have been created and measured in the lab of Prof. Moty Heiblum of the Condensed Matter Physics Department.

Such a system must meet several criteria before it can be considered a possible qubit. The particles must be able to exchange places, and this exchange must leave a sort of trail that can be traced – that is, it must preserve information. In Stern's theoretical experiment, two parallel lines of current run through such a system with a separation "wall" containing quasiparticles between them. An odd number of quasiparticles should cause the electrons in the current to behave as particles, flowing in line through the material. But if they are separated by an even number, the electrons in the system should act as waves, producing interference patterns at the end of the current pathways.

In addition to the number of fractionally charged particles in a system, the fraction itself is relevant. The quasiparticles Heiblum measured in the 1990s had odd denominators, and these don't leave traces when they exchange places in the plane, making them unfit for storing information. Even-denominator fractions might be better for the purpose, but they're harder to produce. This past year, Heiblum and Stern, together with research student Merav Dolev and Drs. Vladimir Umansky and Diana Mahalu, all of the Condensed Matter Physics Department, succeeded in creating a nanoscopic device in which quasiparticles with one-quarter the charge of an electron were measured for the first time. They are now continuing their experiments to find out if quarter-charge quasiparticles are truly suitable candidates for quantum bits.

Can quantum errors be corrected?

Quantum "weirdness" – the strange reality that rules the world of ultra-tiny particles – presents some unique challenges. For instance, how can one perform calculations in a system in which the very act of measurement changes the basic configuration of that system?

Quantum superposition has been demonstrated in particles such as electrons, but it has never been observed in larger objects composed of many particles. The reason, scientists believe, is that in larger groups the particles interact with one another and with their environment, forcing the quantum superposition of the system into a single classical state. (Measurement is one form of interaction.) This transition is called decoherence. One could conceivably build a very simple quantum computer with only a few qubits, but how to create one that has millions?

Since joining the Weizmann Institute in 2007, Dr. Roee Ozeri and his students Nitzan Akerman, Yinnon Glickman, Shlomi Kotler, Yoni Dallal and Anna Keselman have been setting up a lab in the Physics of Complex Systems Department, and they have recently begun to conduct experiments that may one day help overcome the limitations. Ozeri is especially interested in error correction in quantum computing. Today's electronic computers compensate for possible errors by building in redundancy and using error-correction protocols. In analog quantum protocols, different kinds of error correction may help overcome decoherence and keep superpositions of many particle states "alive." Ozeri is also investigating ways of creating complex quantum logic gates – the basic operations of quantum computing – in which actions performed on one qubit can, under the right conditions, change the state of a second. Because quantum systems can't be measured directly without affecting the result, Ozeri must use roundabout methods that ascertain whether there are errors in the qubits' final state.

His experimental quantum system is based on ions – specifically, atoms of the element strontium that have undergone "laser surgery" to remove some of their electrons. Several of these ions are fired into a vacuum chamber, where they're trapped in an array of electrical fields, while another laser cools them to within a few millionths of a degree of absolute zero. Although Ozeri's experiments trap just a few ions at a time, he can examine the effects of decoherence by applying an electromagnetic field to create noise in the ions' environment. For "communicating" with the ions, he uses yet more lasers, which are precisely tuned to interact with various transitions between strontium ion states.

While the challenge of creating the basis of future computers is compelling, it is ultimately the questions of basic physics that Ozeri finds most fascinating: "We've been exploring the physics of the quantum world for around 100 years, and those of macro systems for much longer, but we still don't know much about the point at which one takes over from the other, how the transition happens or whether it's possible to push the limits and extend the quantum superposition principle into many-particle systems. This research might help provide answers to some of these very basic mysteries."

Do quantum codes communicate better?

Have humans beaten nature at its own game? The attempt required a team of scientists using some of the most advanced computer-aided design and biological engineering techniques available, as well as one very ancient technique – evolution. Recently scientists created a new enzyme that performs a function unknown in nature. Compared to the millions of years nature takes to come up with a new enzyme, the scientists managed this feat in hardly any time at all.

 

The team began with the design of the active site – a string of amino acids responsible for the chemical reactions that take place. They then turned their attention to the rest of the enzyme – its backbone. This entailed generating a sequence for the 200 amino acids in its protein structure. While in theory there are a nearly infinite number of ways to arrange the 20 types of amino acid into strings of 200, in practice only a limited number can yield a structure, and thus a mode of action, capable of performing the task.

 

To identify possible sequences for their enzyme, Prof. David Baker of the University of Washington, Seattle, used novel computational methods to scan tens of thousands of computer-designed sequences. Eventually he and his team identified 60 that could potentially facilitate the chemical reaction, and these he tested further to see if they would work in biological systems.

 

 

Of the 60 sequences tested, eight showed signs of biological function and only three made it to a “final round” of the scientists’ challenge by showing a detectable level of activity. At this stage, the enzymes had moved from the computer “drawing board” to the bioengineering lab. Drs. Orly Dym and Shira Albeck of the Weizmann Institute’s Structural Biology Department solved the structure of one of the final contenders, confirming that the structure of the enzymes created was essentially identical to the predicted computational design.

 

Yet even with the benefit of the most advanced computer and bioengineering technologies, the winning enzymes could not compete with the speed and efficiency of their naturally evolved counterparts. At this point, Prof. Dan Tawfik and research student Olga Khersonsky of the Biological Chemistry Department entered the picture. In a twist on natural evolution, they have found that the principles of random mutation and natural selection can be applied in the lab. Test-tube grown enzymes are mutated, and the most efficient ones are selected to undergo further rounds of mutation and selection.

 

At the end of only seven rounds of test-tube evolution, the enzymes’ efficiency had increased 200-fold over those created from the computer design template, and the new enzyme-assisted chemical reaction rates were a million times those taking place with no enzyme at all. While the designed/evolved enzymes are still much slower than their natural counterparts, a comparison of the evolved enzymes to their computer-designed ancestors showed how adjustments to the enzyme structure can increase its efficiency: One near the active site improved the reaction rate, while others increased the molecules’ flexibility, allowing the enzyme to detach faster upon completing a step in the reaction.

 

“The combination of computational design and molecular in vitro evolution opens up new horizons in the creation of synthetic enzymes,” says Tawfik. “Reproducing the breathtaking performance of natural enzymes is a daunting task; but thanks to this research, we have gained a better understanding of the structure of enzymes as well as their mode of action. This, in turn, will allow us to design and create enzymes that nature itself has not ‘thought’ of. The possibilities are nearly endless: neutralizing poisons, developing medicines and future applications that we ourselves have not yet imagined.”  

 

Prof. Dan Tawfik’s research is supported by the J&R Center for Scientific Research; the Wolfson Family Charitable Trust; the Jack Wolgin Prize for Scientific Excellence; Mr. and Mrs. Yossie Hollander, Israel; Rowland Schaefer, New York, NY; and the estate of Fannie Sherr, New York, NY.