化学与分子工程学院学术报告

题目：Genotypic Variability and the Quantitative Proteotype

讲座人：Prof. Ruedi Aebersold

Department of Biology, Institute of Molecular Systems Biology,

ETH Zurich and Faculty of Science, University of Zurich

时间：2015年5月29日，14:00

地点：化学楼A204/206报告厅

联系人：刘小云

Abstract:

The question how genetic variability is translated into phenotypes is fundamental in biology and medicine. Powerful genomic technologies now determine genetic variability at a genomic level and at unprecedented speed, accuracy and (low) cost. To date the effects of genomic variability on the expressed information of the cell has been mainly studied by transcript profiling.

In this presentation we will discuss emerging computational and quantitative proteomic technologies to relate genotypic variation to the proteome. Proteomic data to support such correlations need to be quantitatively accurate, highly reproducible across multiple measurements and samples and generated at high throughput.  Ideally, the data also would provide information about spatial arrangement of proteins in the cell. Data with these qualities can now be generated by the targeted proteomic methods selected reaction monitoring (SRM) and, at higher throughput, by SWATH-MS (1) and by chemical cross linking and mass spectrometry (XL-MS) (2)

We will discuss the principles of these mass spectrometric methods, discuss the computational challenged they pose for data analysis and demonstrate with selected applications, using genetic reference strain compendia, their ability to determine the effect of genetic variability on the quantitative proteome, thus functionally connecting the genome to the proteome (3,4).  

1.Gillet LC, Navarro P, Tate S, Roest H, Selevsek N, Reiter L, Bonner R, Aebersold R. (2012) Targeted data extraction of the MS/MS spectra generated by data independent acquisition: a new concept for consistent and accurate proteome analysis (2012). Mol Cell Proteomics 11:O111.016717.

2.Herzog F, Kahraman A, Boehringer D, Mak R, Bracher A, Walzthoeni T, Leitner A, Beck M, Hartl FU, Ban N, Malmström L, Aebersold R. (2012) Structural probing of a protein phosphatase 2A network by chemical cross-linking and mass spectrometry. Science. 2012 Sep 14;337(6100):1348-52. doi: 10.1126/science.1221483.

3.Picotti P, Clément-Ziza M, Lam H, Campbell DS, Schmidt A, Deutsch EW, Röst H, Sun Z, Rinner O, Reiter L, Shen Q, Michaelson JJ, Frei A, Alberti S, Kusebauch U, Wollscheid B, Moritz RL, Beyer A, Aebersold R.  (2013)  A complete mass-spectrometric map of the yeast proteome applied to quantitative tranalysis. Nature. 494(7436):266-70.

4.Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population (2014). Wu Y, Williams EG, Dubuis S, Mottis A, Jovaisaite V, Houten SM, Argmann CA, Faridi P, Wolski W, Kutalik Z, Zamboni N, Auwerx J, Aebersold R. Cell. 158(6):1415-30. doi: 10.1016/j.cell.2014.07.039.

Bio:

Prof. Ruedi Aebersold is one of the pioneers in the field of proteomics. He is known for developing a series of methods that have found wide application in analytical protein chemistry and proteomics like a new class of reagents termed Isotope Coded Affinity Tag (ICAT) reagents used in quantitative mass spectrometry. Prof. Dr. Aebersold and his team of researchers use the protein profiles determined by this method to differentiate cells in different states, such as noncancerous versus cancerous cells, and to systematically study how cells respond to external stimuli. These "snapshot" profiles indicate which cells contain abnormal levels of certain proteins. This is expected to lead to new diagnostic markers for disease and to a more complete understanding of the biochemical processes that control and constitute cell physiology.

Prof. Aebersold serves on the Scientific Advisory Committees of numerous academic and private sector research organizations and is a member of several editorial boards in the fields of protein science, genomics, and proteomics.

Prof. Aebersold is a native of Switzerland and obtained his Ph.D. in Cellular Biology at the Biocenter of the University of Basel in 1983. Since that time, he is a faculty member of the Universities of Washington and British Columbia, until 2000, when he co-founded the Institute for Systems Biology in Seattle. In 2004, he accepted a position as full professor at the Institute of Biotechnology at the Swiss Federal Institute of Technology (ETH) in Zurich, where in January 2005, his research group became the first integral part of the newly founded Institute of Molecular Systems Biology.

欢迎各位老师同学积极参加！