Workshop Proposal:
Wednesday, 24


Genomics, Proteomics and Peptidomics of the Secretory Pathway.

Eiden, Lee (USA)         Anouar, Youssef (France)

Speaker 1:

Anouar, Youssef (Mont-Saint-Aignan, France)
"Genomics and proteomics of the chromaffin cell: characterization of cell differentiation and chromogranin peptide formation ".

Speaker 2

Lee, Jean (San Diego, USA)
"Proteomic studies of the chromaffin granule demonstrates novel proteolytic processing mechanisms for chromogranins and proenkephalin by secretory vesicle cathepsin l".

Speaker 3

Shaw, Chris (Ulster, United Kingdom)
"Chromogranin peptidomics: functional fingerprints of secretory proteins in tissue and plasma".

Speaker 4

Haycock, John (Louisiana, USA)
"Phosphoproteomics of signal transduction regulating catecholamine biosynthesis".

Speaker 5

Eiden, Lee (Bethesta, USA)
"Proteomics, genomics and peptidomics of the chromaffin cell--where do we stand in 2003?".

Short description:
The theme of the workshop is chromaffin cell proteomics. The major objectives are to build on the 2002 ISCCB-11 Workshop on "Computing the Chromaffin Cell" to complete the objectives set out during that workshop (see "Computing the Chromaffin Cell: A Research-Commuity Curator/User Approach to Biocomputation for Chromaffin Cell Biology" by Lee E. Eiden and Michael D. Hirsch). That Workshop introduced various computational tools for improving data analysis, data mining, and experimental design in chromaffin cell research, including the Samuel Lunenfeld Institute's BIND database; Science's Signal Transduction Knowledge Environment/C-MADES-based Connections Maps; Molecular Sciences Institute/National Institute of Mental Health's pathFinder static pathway analysis tool, now installed as a web-based chromaffin-cell based informatics tool, the Virtual Cell simulation package for imaging and predicting calcium, cAMP and other second messenger dynamics in neuroendocrine cells and neurons; Ravi Iyengar's and Bjorn Obrink's computational approaches to signaling pathway analysis using restricted kinetic and thermodynamic data sets; Ricardo Borges-Jurado's amperometric spike analysis software; and Kathryn Resing's 2D PAGE/mass spectrometry approach to phosphoproteomics signaling in mammalian cells. Progress has been quite substantial as a result of this workshop. Six goals for establishing a working chromaffin cell user/curator bioinformatics group (see "Computing the Chromaffin Cell", ibid) are each being developed as planned. Specifically, the STKE now has a PC12 cell Connections Map (see D. Vaudry et al., Science 296: 1648-9, 2002); Lee Eiden and Phil Marley are working up a second Connections Map on "Signaling During Exocytosis"; and pathFinder is now available for chromaffin cell signaling analysis at

With better communication within the chromaffin cell research community afforded by a Website, and access to common bioinformatics tools, chromaffin cell laboratories have been able to make additional informal progress since the last meeting relevant biocomputation in chromaffin cell research. In this sense, the Workshop proposed here has been ongoing in silico since September 2001. An emerging consensus is that proteomics, in particular phosphoproteomics, is the most useful focus for chromaffin cell practicioners at this point, for three reasons. First, bovine protein databases have the potential to support phosphoproteomics (>80,000 bovine ESTs, according to an informal analysis of bovine protein sequences currently available in GenBank, SwissProt and other sequence databases by Liangbiao Chen, Zhejiang University, China, performed January, 2002). Second, bioinformaticists are beginning to integrate genomics and proteomics databases to provide additional support for both LC/genomic and PAGE/proteomic approaches to identification of regulatory molecules involved in neuroendocrine signaling. Finally, the chromaffin cell, and its "paralog", the PC12 cell, is the premier cell model for secretion and trans-synaptic regulation of gene transcription for neuroendocrine cells, providing a sufficiently abundant and pure population of cells for biochemical analysis, which have been thoroughly studied vis-a-vis their secretory and trans-synaptic signaling properties (see Introduction to "Computing the Chromaffin Cell", ibid.).

This Workshop is therefore an excellent opportunity to bring together the foremost practicioners of neuroendocrine cell biology (Drs. Ahlmers, Sudhof, Winkler, Fischer-Colbrie, Neher, and Wightman are internationally recognized chromaffin cell researchers and participants in ISCCB-11 and/or ISCCB-12) with bioinformaticists and proteomics practicioners (see below) to provide an historically unique infusion of bioinformatics/proteomics into a field that has considerable momentum already in cell biology, real-time imaging, and biochemistry, to focus on critically important problems of secretion and trans-synaptic gene regulation that have eluded full understanding till now. These include the relationship between vesicle biogenesis and full and partial exocytosis discharge; the role of synaptotagmin-like calcium sensors in small versus large vesicle exocytosis; the combinatorial regulation of stimulus-secretion-synthesis coupling across neuroendocrine and neuronal synapses, and the regulation of synaptic versus post-synaptic and cellular plasticity.


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