Blueprint for a new age

December 21, 2001

The decoding of the human genome has helped to deliver the molecular motors that will drive the technologies of the future, writes John Walker.

The decoding of the human genome is an enormous achievement that will influence the courses of chemistry, biology and medicine in the 21st century. The number of genes in the genome is still being debated, but it may be about 40,000. Different ways of joining together the pieces of genes called exons ensure that the number of proteins encoded in the genome is much higher than 40,000. Subsequent biochemical modifications of the proteins add more complexity. The functions of the majority of these proteins are unknown. The next major task will be to determine the role each plays in the life of the hundred thousand billion cells that make up our bodies.

Each second, millions of our cells divide. The set of events from one division to the next is called the cell cycle. The cell grows. It copies the DNA in the chromosomes, and it divides into two daughters. This complex process is regulated by an enzyme known as cyclin dependent kinase (CDK), a kind of molecular engine that drives the cell through its cycle by modulating the shapes and functions of other cellular proteins. The CDK engine is turned on and off by a molecular switch protein called cyclin. The importance of unravelling these fundamental events was recognised recently by the awarding of this year's Nobel to Paul Nurse, Tim Hunt and Lee Hartwell (page XVI).

Other biological machines are involved directly in copying the DNA molecules during the cell cycle, and in transcribing the instructions in DNA into the messenger RNA molecules. The mRNAs are decodified by another complex molecular machine known as the ribosome. The ribosome reads the code in the mRNA three letters at a time and uses it to specify the order of the 20 possible building blocks (the amino acids) that make up the linear strand of each of the proteins. The ribosome and the mRNA, together with other essential molecules, act as an assembly line to make proteins from the amino acids. Yet another molecular machine helps the linear protein products from the assembly line to fold up into their correct shapes in three-dimensional space, thereby enabling them to assume their particular functions.

These molecular machines, and the many others that make biology work, need fuel. The fuel comes from the food we eat, which feeds tiny power houses (the mitochondria) in our cells. They oxidise (burn) molecules derived from carbohydrates and fats in food, and in the process consume most of the oxygen that we breathe in. The energy released by oxidation is used in the mitochondria to drive another molecular machine that generates the energy currency of biology, a small molecule called adenosine triphosphate. This ATP is distributed from the mitochondria throughout the cell and supplies the molecular machines with the fuel to make them work. It is certain that as the functions of more proteins are revealed many of them will turn out to be components of as yet undiscovered biological machines.

By taking still snapshots of molecular motors using a technique called X-ray crystallography, we are beginning to understand what they do, how they are put together and how they function. One biological machine called kinesin is processive and advances along protein tracks in our cells, delivering cargo to the correct places. The machine at the heart of our muscles acts like a rowing machine, dipping in its oars, gaining purchase, advancing, and then raising its oars before starting the cycle again. The machine that produces ATP has a kind of turbine at its heart. The turbine rotates a shaft at about 100 times a second and impels an attached synthetic engine. The machine that helps to give proteins their shapes acts as a two-cylinder engine. Other molecular machines act as pumps for small ions, driving them across biological membranes, helping, for example, to make our brains work. Like the much larger machines and engines of everyday life, the molecular machines of biology have moving parts that act as bearings, hinges, switches, clamps, valves, diaphragms and cogs. One even has a device that acts like the escapement of a mechanical clock. As in clocks, molecular springs store energy and release it in a controlled manner. A major difference between molecular machines and their macroscopic counterparts is that they are made from one material only, proteins, whereas in the construction of macroscopic machines a wide variety of metals and plastics with a wide range of mechanical and electrical properties are employed. So one area that we need to understand is how proteins are able to provide the range of physical properties needed to make the molecular machines work. Increased understanding in this area could help to provide ideas for improved or new materials.

We are just beginning to unravel the dynamic aspects of molecular machines that we need for a deeper understanding of how they function. From this kind of study, new details and even new principles of molecular motors should emerge. This new knowledge should in turn influence the design and construction of new nano-scale devices for use in applied industrial settings. Such activities have begun already. Simple molecular motors that rotate or move back and forth in a linear manner have been synthesised chemically from small molecules and are likely to be the precursors of much more sophisticated nano-scale devices. Just as present-day aeroplane design has been influenced and inspired by creatures in the biological world, it is not too fanciful to suppose that the design of nano-scale devices will be influenced by the biological molecular creatures that are beginning to come to light.

Sir John Walker was awarded the Nobel prize for chemistry in 1997.

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