The Siena Proteome conference has a special significance in the development of the new field of proteomics. At the first Siena conference in 1994, Marc Wilkins used the term “Proteome” for the first time in public. The second Siena conference in 1996 saw the first fruits of proteomics, which at that time were more in the form of promises of things to come, rather than what we know of the field today. This volume will be in the conference satchels for the third Siena Proteome conference, and it heralds many new things, while also giving a perspective on how the field has developed. We can confidently anticipate that the papers at the third conference will reveal yet a further quantum leap!

Reviews

This issue commences with five reviews. The review by Anderson and Anderson charts the origins of proteomics, its potential, and its challenges. The review by Haynes et al. covers similar territory but with more focus on the enabling proteo- mics technologies. The third review by Packer and Harrison overviews an emerging theme in proteomics, that of post-translational modifications. Undoubtedly this will become more important in the near future, as there are limited ways of studying modifications on a global scale by any technology other than proteomics. A review by Walsh et al. discusses the establishment of the world’s first national proteomics facility, the Australian Proteome Analysis Facility. Finally, Hubbard reviews studies on a most challenging tissue, enamel cells from developing rat teeth. From this work have come new findings on calcium transport which are relevant to all tissues in the body.

Proteome technology

There follow six papers describing technology developments that either improve proteomics or suggest steps towards automation. The issue of sample preparation is elegantly addressed by Chevallet et al. who have taken up the challenge of getting insoluble samples solubilised, and to migrate in both the first and second dimen- sions of the two-dimensional (2-D) gel. New detergents are described which solubi- lise membrane proteins. Reflecting the huge developments in mass spectrometry, the other five papers address various aspects of mass spectrometric identification of proteins and glycoproteins. The paper by Kratzer et at. addresses an important issue in protein identification using peptide mass fingerprinting. In a systematic study, suppression of peptide signals in peptide mixtures is investigated. The paper by

Parker et al. addresses the issue of large-scale protein identification from 2-D gels. Technical challenges such as contaminating proteins as well as informatics issues are dealt with. The paper by Korostensky et al. describes a chemical or enzymatic approach to generating sequence tags, and algorithms which support database searching. This paper begins to address fully automated peptide mass analysis. The paper by Traini et al. describes a first pass at “hands off sample handling and pep- tide mass fingerprinting identification routines. Finally the paper by Kiister et al. presents structure determination of N-linked sugars using matrix assisted laser desorption/ionisation (MALDI) mass spectrometry.

Applications of proteomics

There follow twelve papers on applications of proteome technology. Three papers address microbial issues. The first by Tonella et al. is an update of the SWISS 2D-PAGE Escherichia coli database. This is the proteome equivalent of genomics, where large-scale protein identification is the goal, with the 2-D gel as the map. The second paper by Guerreiro et al. is a more focused proteome on proteins found in Rhizobium leguminosarum that result from the presence of different combinations of endogenous plasmids. The third paper by Evers et al. involves understanding how antibiotics affect proteins of Haemophilus influenzae; pathways related to amino acid metabolism were investigated.

The remaining nine papers address aspects of animal cell or animal tissue pro- teomes. The paper by Nygaard et al. describes an elegant method for characterisa- tion of recombinant secreted proteins expressed in BHK cells. The paper by Aicher et al. addresses toxicity in kidneys caused by cyclosporine A. The involvement of a calcium binding protein, calbindin-D, in cyclosporine toxicity is a direct outcome of the proteome studies. The paper by Hanash and Teichroew describes the establish- ment of high quality 2-D gel maps of human lymphoid cells and the formation of a database consisting of 9 167 individual 2-D patterns. The challenge of mining this huge database remains daunting. In fact, this paper is a cry for help to the bioinfor- maticists, as currently the data can only be reliably mined in a manual fashion, one protein at a time. Post-translational modifications are addressed in the paper by Magi et al. where it is elegantly shown that the macrophage migratory inhibitory factor is different from its predicted p l and that different forms are found in human liver and breast. Jensen and Celis address a transgenic mouse model that involves a degenerative disorder of myelin. This paper uncovers a number of candidate marker proteins for neurological disease. Three papers by Heinke et al., Corbett et al. and Pleissner et al. address various aspects of heart disease by differential proteome analysis of normal and diseased hearts.

It is obvious from the above snapshots of the papers in this issue that proteomics addresses a broad range of biology. In fact, it is relevant to all studies on complex biological problems. It is also interesting that the application of proteomics has already moved into industry since almost a quarter of the papers in this issue come from industry groups. I would like to thank all of the authors for agreeing to con- tribute to this issue and for their timely submission of manuscripst, often under dif- ficult conditions. Special thanks to Sue Graves who has made order out of chaos in my preparations for this volume.

Keith Williams Guest Editor