Wai Man, Bill Neville, Mark. Skehel and Ian White ... R.Huganir John Hopkins Uni Medical School, 72511 Wolfe Street,. Precinct B905 Baltimore USA MD21205.
Biochemical Society Transactions (1999) 27
C9
Proteomics in Pharmaceutical Research and Development
Paul Cutler, Helen Birrell, Margaret Haran. Wai Man, Bill Neville, Mark Skehel and Ian White Smith Kline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue. Harlow, ESSEX, CM19 5AW UK.
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A69
Organisation of Synaptic Structure in the Brain
R.Huganir John Hopkins Uni Medical School, 72511 Wolfe Street, Precinct B905 Baltimore USA MD21205
The advent of genomics has led to a rapid rise in DNA data available. Several simple organisms have now been completely sequenced.The function of the genes however remains for the most part undetermined. It is clear that identification of gene function will only become unequivocal by studying the functional gene product - the protein [I]. An understanding of gene regulatory processes. post-translational modification etc., particularly in higher organisms, make the study of protein expression crucial in understanding biological systems [2]. Proteomics is an evolving discipline which utilises state of the art technology in protein separation, especially 2D PAGE, image analysis. chemometrics and bioinformatics to analyse complex biological systems and elucidate the effects of endogenous and exogenous stimuli. Proteomics is therefore valuable in achieving a better understanding of physiological, pharmacological and toxicological processes and has the potential for delineating mechanisms not possible by other techniques. The rapid advance of technologies has allowed the application to several aspects within the commercial drug pipeline. Proteomics has many proven applications to drug discovery. These include the verification of protein expression following gene transfection, target identification [3] and defining mechanisms of drug action [4]. Numerous applications exist for proteomic analysis in development including the characterisation of biopharmaceuticals, defining clinical markers [ 5 ] and profiling mechanisms of toxicity
[61.
[ I ] Humphrey-Smith and Blackstock (1997) J. hot. Chem. 1 6 537-544;[2] Parekh and Rohlff (1997) Cum. Op. Biotcch. 8: 718-723; [3] Bini et al.. (1996) Electrophoresis 17: 185-190 141 Dainese et al., (1997) Electrophoresis 18: 432442; 151 Young and Tracy (1995) J. Chromatography 698: 163-179[6] Arnott et al.. (1998) Anal. Biochem. 258: 1-18
C10
Nanotechnology Proteomics
Approaches
to
Johan Roeraade, Royal Institute of Technology Dept of Analytical Chemistry. SE- 100 44 Stockholm - Sweden Proteomics is an area with an explosive growth. The development of analytical tools for complex protein mixtures is of particular importance for the drug industry, to improve the understanding of drugprotein interactions. Some of the major issues in this context are enhanced resolution. enhanced dynamic range between detection and overload and throughput (including sequencing). Nanotechnology, using chip-based chcmistry has a great potential in proteomics. For example, miniaturized vials with volumes down to 100 pL can he employed to carry out proteolytic degradations of proteins. The advantage of the reduced volume is that a high concentration of material is maintained, even when dealing with trace amounts of material. This promotes reaction kinetics. Examples of such reactions will be shown, ns well as different technologies to handle and tranfer very small amounts of material. Nanorobotics are employcd to obtain precision multi-positioning, along with arrays of microcapillaries or ink-jet - like dispensing devices. Matrices of c.g. 500.000 picovials in silicon or glass can be produced with photolithographic definition and subsequent etching procedures. A basic platform for ultra-high throughput is thus obtained. However, a number of critical factors must be considered when working with reduced volume systems. This includes problems like solvent evaporation, surface activity, mass transport and adsorbtion. Several new concepts, to deal with these problems will be presented.
D2
The Molecular Organisation of the Post-Synaptic Membrane in Excitatory Synapses
M.Sheng Lab of Neuroscience, RM 243, 50 Blossom Street, Boston, USA, MA021 14
