Scientists who have accepted an invitation to contribute sent early 2006

Wolfgang Baumeister, Munich; Terese Bergfors, Uppsala; David Eisenberg, UCLA, CA; Carola Hunte, Leeds; Louise N. Johnson, Oxford; Yvonne Jones, Oxford; Werner Kuhlbrandt, Frankfurt; Lars Liljas, Uppsala; Helen Saibil, London;Thomas Steitz, New Haven, CT; Robert Stroud, UCSF, CA; David Stuart, Oxford; Janet Thornton, Hinxton; Ada Yonath, Rehovot; additional speakers will be chosen according to exciting and innovative results coming up in the literature.

Scientific justification


Almost weekly, international journals such as Nature, Science, Cell show striking drawings of large biological molecules, and the articles therein explain the role and functions of these macromolecules. Indeed the realisation of the huge international investment in defining the genome sequences of living organisms of man, of model systems and of the agents of disease depends on a description of the spatial and temporal dimensions of macromolecules and their complexes in the cell, the research area known as structural biology, a largely prevalent section of crystallographic literature. In recent years there has been a focus on structural genomics: the reductionist definition of the architectures of representative gene products in different organisms.

There has also been progress in the characterisation of many molecular machines, such as the ribosome and the proteasome, of complex assemblies of proteins controlling the passage of nutrients, proteins and other molecules across membranes, and of transient multiprotein systems, involved in cell regulation. Finally there is progress in understanding the arrangement of these systems within the cell. Many of these macromolecular structures and assemblies are central to understanding disease processes and their consequences for the living organisms. Increasingly they provide useful knowledge as to how they might be targeted by drugs, both small chemical entities and large biological molecules. Others contain information on which to base the design of vaccines. Crystallographic studies on cell membrane proteins enlighten the ion permeation of cellular water channels, which are involved in the proper functioning of the nervous system and the muscles. The pioneering work by D. Sayre and his coworkers on single particles structure promises a variety of new discoveries. Thus the structural information is being used in academia and industry, small biotechnology start-ups and large pharmaceutical companies to design agents to combat Alzheimers, Parkinson's Disease, cancers, rheumatoid arthritis and many viral infections including HIV and influenza, a whole range of devastating diseases that cause untold misery, extracting both monetary and human tolls.

The structure determination of viruses by X-ray crystallography, cryo-electron microscopy and NMR has aided our understanding of how they infect cells, and the knowledge of viral structure is a powerful tool for the development of new strategies to prevent viral infections. This highly focused Course will discuss strategies for using macromolecular structures and assemblies not only to understand how healthy cells function, but also to identify errors that occur in diseases and then target the proteins with useful drugs.

Topics

. Evolving methods; Robotics for protein expression, purification, structure determination and imaging; CryoEM, single particle analysis and tomography; Computer modelling bringing together results of individual molecules, assemblies and cells; RNA and DNA replication and synthesis; Progress in structural genomics; Multicomponent machines involved in protein biosynthesis and processing; Membrane proteins, pores and transporters; Transient multiprotein systems involving growth factor receptors, signal transducing assemblies and nucleic acid-protein complexes; Amyloid structure; Viruses and virulence factors; Slot open to future hot topics