Sir aaron klug biography template

My watch list My saved searches My saved topics My newsletter Register free of charge. Keep logged in. Login Register. Additional recommended knowledge. Press release. Retrieved on State of South Africa 29 September Almost half a century had elapsed before the technique of X-ray diffraction had developed to a point allowing the determination of the structure of the giant molecules that are the building blocks of life.

The aim of their field of structural molecular biology was to describe the biological machinery in molecular, i. The publication of the structure of haemoglobin at 6-angstrom resolution by Perutz and his collaborators along with Kendrew's findings on the myoglobin molecule at 2-angstrom resolution in Nature, inheralded a new era in biology, marked inwhen Max Perutz and John Kendrew were awarded the Nobel Prize for the first solution of the structure of proteins.

Virus particles: structure and assembly Klug's first major contribution to molecular biology, together with Donald Caspar, a collaborator of Jim Watson in Yale, was to explain in how the protein shells of spherical viruses are constructed from large numbers of apparently identical subunits. InKlug and Finch had taken up the X-ray analysis of spherical viruses that had been investigated by Bernal's group just before and after World War II.

With sufficiently high resolution X-ray and electron microscopy they found in more than one case that what appeared to be spherical viruses, actually displayed full icosahedral symmetry, arguably the highest symmetry shown in Nature. InCrick and Watson had proposed that small isometric viruses should form an isometric shell around the nucleic acid.

The largest number of subunits that could be arranged symmetrically on the surface would be 60, with icosahedral symmetry, as was indeed indicated by X-ray patterns and electron microscope images. However, Caspar and Klug found that the number of subunits in most virus shells was considerably larger than To resolve this dilemma, after reading about the large geodesic domes designed by the American engineer Buckminster Fuller, they imagined the virus shells spread out as flat hexagonal networks that could be cut and folded to form larger and larger icosahedra and proposed that the equivalent bonding required by exact symmetry could be relaxed to what they termed 'quasi-equivalence' and thus accommodate some multiples of 60 subunits.

The concept of self-assembly underlying the principle of quasi-equivalence that had helped to interpret the structures of spherical viruses materialised in the surface patterns appearing in photographs of spherical viruses taken through an electron microscope. Klug also studied the phenomenon of self-assembly both experimentally and theoretically in the case of the tobacco mosaic virus, the classical example of a rod-shape virus.

After Franklin's death, Klug continued and extended its X-ray analysis with John Finch and Kenneth Holmes, who were then students, and who became colleagues. The determination of such a large structure by X-ray methods posed formidable technical and analytical problems. By the early s, Klug came to realise that a way around this difficulty was to try to crystallise the isolated protein subunit of the virus, solve its structure by X-ray diffraction and then try to relate this to the virus structure solved to low resolution.

The rod shape of TMV results from its basic design, namely a regular helical array of identical protein subunits, into which is embedded a single molecule of RNA wound as a helix. It is, of course, the RNA that carries the genetic information, i. The geometry of the protein arrangement forces the RNA backbone into a moderately extended single-strand configuration.

Running up the central axis of the virus particle is a cylindrical hole with a angstrom diameter, which they then thought to be a trivial consequence of the protein packing, but it turned out to figure prominently in the story of the assembly. This general picture was already complete bywhen Rosalind Franklin died, and at sir aaron klug biography template sight, it seemed easy to understand how a helical structure like that of TMV might be built out of identical subunits making identical contacts with its neighbours so that the bonding between them repeats over and over again, assembling themselves by repeated identical interactions.

This would be like adding steps in a spiral staircase in a unique way, enclosing the RNA as a corkscrew-like thread as the rod extends. It was thus not surprising that tobacco mosaic virus could be reassembled from its isolated protein and nucleic acid components. By simple remixing, infectious virus particles were formed that were structurally indistinguishable from the original virus.

The sir aaron klug biography template apparently satisfactory picture described above is actually wrong. When the RNA and the coat protein of the virus are taken apart, the assembly of the virus revealed a much more complex process than might have been expected from the simplicity of the helical design of the particle. InKlug and his collaborators discovered the existence of two juxtaposed layers, or rings, of 17 protein subunits each, that Klug named the two-layer disk.

How could a closed-ring structure be related to the helix assembly? The structure had clearly a geometry related to that of the virus particle and the results coming from growing data at disposal made him wonder whether the disk aggregate might not be fulfilling some vital biological role. Although the structure of the disk was solved in detail only inan earlier stage in the X-ray analysis gave the clue as to how it might interact with the RNA.

The disk aggregate of protein actually had a number of significant properties that strengthened Klug's conviction that the disk form might play a significant role in the assembly of the virus. Assembly of any large aggregate of identical units, such as a crystal, can be considered from the physical point of view in two stages: first nucleation and then the subsequent growth.

The problem was to understand how the mode of initiation, in which the free RNA interacts with individual proteins subunits, was getting started. The protein actually forms an obligatory intermediate, the cylindrical disk composed of two layers of protein units, in which the packing of the subunits differs somewhat from the arrangement in the complete virus containing both RNA and protein.

The disk is designed to permit the RNA to enter through the central hole, and the growth of the virus is initiated with the binding or attachment of the specific sequence of the viral RNA to the protein disk, leading to the recognition by the disk during the nucleation process. These experiments showed that the formation of the protein disk is the key to the mechanism of the assembly of TMV.

In representing an intermediate subassembly, the disk is both the nucleus - attracting an initiation sequence in the viral RNA - and the building unit for growth of the virus rod. It provided an extraordinary mechanism by means of which the difficult problem of simultaneously fulfilling the physical requirement for nucleating the growth of the helical particle and the biological requirement for specific recognition of the viral RNA.

Due to the crucial role that the protein disk plays in the assembly of the virus from its RNA and protein, the crystallographic analysis required the combined efforts of Klug and many co-workers, as well as new computer methods. This was the first very large structure ever to be tackled in detail by X-ray analysis and it took about a dozen years to carry through the analysis to high resolution.

The formidable technical problems were overcome only after the development of more powerful X-ray tubes and of special apparatus cameras, computer-linked densitometers for data collection from a structure of this magnitude. Init was possible to construct an atomic model showing the detailed structure of the protein subunit and how it interacts with its neighbours and to elucidate the process of self-assembly of such partial structures to give the complete virus.

This process, together with the solution of the structure of the flat doughnut-shaped protein disks by X-ray analysis, yielded a full description of the protein and RNA interaction, giving a great contribution to the understanding of how proteins and nucleic acids interact. The general conclusion derived from the story of the tobacco mosaic virus assembly was that one must distinguish between the design of a structure and the construction process used to achieve it.

It illustrates the point that function is inextricably linked with structure and shows how much can be done by one single protein. He applied for a research position at the Cavendish Laboratory, but due to limited availability, he ended up studying the molecular structure of steel under the supervision of D. Inhe obtained his doctorate for this work.

InKlug joined the Department of Colloid Chemistry at the University of Cambridge, where he began researching the biophysical processes of oxygen and carbon dioxide exchange in hemoglobin. This research further fueled his interest in X-ray analysis of biological molecules. Inhe became the head of a research group at Birkbeck College, University of London, studying the structure of the tobacco mosaic virus.

InKlug developed a method called crystallographic electron microscopy, which combined electron microscopy with laser diffraction to determine the structure of biological complexes.

Sir aaron klug biography template

This method allowed him to study the complex organization of cells and molecules, providing valuable insights into the nature of cancer and genetic information. This experience aroused a lifelong interest in the study of viruses, and during his time there he made discoveries in the structure [ 6 ] of the tobacco mosaic virus. Over the following decade Klug used methods from X-ray diffractionmicroscopy and structural modelling to develop crystallographic electron microscopy in which a sequence of two-dimensional images of crystals taken from different angles are combined to produce three-dimensional images of the target.

He studied the structure of transfer RNAand found what is known as zinc fingers as well as the neurofibrils in Alzheimer's disease. Also inKlug became a Fellow of Peterhouse, Cambridge. He was later made an Honorary Fellow of the college. Between andKlug was director of the LMB. He served [ when? He was knighted by Elizabeth II in He was elected its President PRS from to He was appointed to the Order of Merit in — as is customary for Presidents of the Royal Society.

His certificate of election to the Royal Society reads:. Mathematical physicist and crystallographer distinguished for his contributions to molecular biology, especially the structure of viruses. Development of a theory of simultaneous temperature and phase changes in steels led him to apply related mathematical methods to the problem of diffusion and chemical reactions of gases in thin layers of haemoglobin solutions and in red blood cells.

Then the late Rosalind Franklin introduced him to the x-ray study of tobacco mosaic virus to which he contributed by his application and further development of Cochran and Crick 's theory of diffraction from helical chain molecules. Klug's most important work is concerned with the structure of spherical viruses. Together with D. Caspar he developed a general theory of spherical shells built up of a regular array of asymmetric particles.

Klug and his collaborators verified the theory by x-ray and electron microscope studies, thereby revealing new and hitherto unsuspected features of virus structure. Klug was associated with the university and the town of Be'er Shevahaving visited them numerous times. Klug married Liebe Bobrow in ; [ 4 ] they had two sons, one of whom predeceased them in Though Klug had faced discrimination in South Africa, he remained religious and according to Sydney Brennerhe became more religious in his older age.

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