Keynote:
Decoding Drivers of Human Disease by Proteomics and Protein Network Building
Peter Jackson PhD, Professor of Microbiology and Immunology - Baxter Labs, Stanford University Medical Center
| Mendelian genetics and extensive genomics have helped define critical genes underlying human diseases, like cystic fibrosis and the susceptibility to cancer. Recent studies have shifted the traditional Mendelian paradigm to encompass more complex models of genetic inheritance, with multiple gene variants contributing to disease. Identifying these complex determinants is not immediately clear from genomic analysis, but requires additional functional information to link multigenic causes to specific pathways. Building a protein interaction network providea a critical map to link multiple gene variants that contribute to complex drivers of disease. Using recombination-based (Gateway, FlpIn) technology, we have constructed a high throughput protocol for cell line construction, mass spectrometric identification of proteins, and assembly of protein interaction networks. Using human disease variants, we can determine deficiencies in the network and provide key insight into new disease drivers. The methods provide both diagnostics and new targets for disease intervention. We have focused on human genetic disease including ciliopathies like Bardet-Biedl and Joubert syndromes. By targeting all known disease gene mutants, we have been able to identify additional protein factors and candidate disease genes. To date, we have found over 20 new disease genes. Network studies on cancer drivers are finding key mechanisms linking non-small cell lung cancer to components of the Ral GTPase pathway. |
Sponsor Seminars, 1-2pm. Select during registration
| Agilent |
Targeted Protein and Peptide Quantitation using Skyline Software Sample complexity and low concentration of some biomarkers are the main challenges in the multiple reaction monitoring (MRM)-based biomarker verification methodology. Consequently, the development of MRM-based methods in biological matrix has focused on improving the sensitivity and increasing the dynamic range, and improving the robustness in the high-throughput clinical research environments. This work demonstrates a novel targeted protein/peptide quantitation workflow which incorporates data independent All Ions MS/MS technique and fully integrated skyline software to achieve straightforward development of an MRM method. The sensitive and robust determination of human plasma peptides using a newly designed Triple-Quadrupole-Mass-Spectrometer is also achieved. |
| Bruker |
MALDI Imaging is Ready for its Close-up MALDI imaging provides a new powerful tool in cancer research, drug development etc, by enabling histological correlation of molecular phenotypes and correlations of molecular signals to clinical endpoints. MALDI Imaging is perfectly suitable for study the distribution of lipids, protein and secondary metabolites in plants. This seminar will provide an overview of current MALDI imaging workflow, Bruker software package, and real clinical imaging examples in drug and cancer research as well as the cutting edge features of Bruker MALDI-TOF instrumentation |
| Metabolon |
Problem Solving with Metabolomics: Completing the Phenotypic Picture in Systems Biology and Disease Metabolomics is the science of deriving biological understanding through the systematic survey of small molecules in a biological sample. Metabolites are central to the physiological state of a living system whether induced by the environment, microbiome or via gene function and result from cellular processes therein. Consequently, metabolites yield a wealth of insight for understanding phenotypic changes in a living system, unlocking disease complexity and are also a rich source for identifying biomarkers. Metabolomics has proven to be effective in understanding bioprocesses including bacteria, yeast, algae, plant and mammalian cell expression systems. In addition, metabolomics can be essential to investigating the role that nutritional components and physiologic stressors play in health, health maintenance, and disease. While there is no doubt that there is a rise in enthusiasm for metabolomics, a persistent bias slowing its widespread use exists. This barrier- our obsession with genomics—is best articulated by David Wishart, "In the world of 'omics' science, metabolomics is like a mouse among elephants" (MetaboNews 2013). Come join this active discussion and learn how metabolomics can be applied effectively to advance research and complete the 'omics' picture. |
| Shimadzu |
The Laboratory of the Future: Next Generation Sample Preparation, Immuno-Mass Spectrometry and Hosted Informatics Solutions This presentation will provide a closer look at the tools, technologies and techniques that are greatly impacting laboratory workflows. We will begin by presenting powerful, new “lab-on-a-card” sample preparation technologies and move into ultra-fast, fully automated, biological and immuno-selective analysis platforms and assess their impact on both small molecule and large protein analyses. Please join us for this interactive presentation where you will discover a new Noviplex Card technology that enables rapid plasma generation in just minutes without the need for venipuncture, centrifugations, etc. This presentation will also introduce Perfinity Workstation and integrated Digestion Platform (iDP) technologies that enable automated, reproducible protein digests on a sub-minute timescale, greatly improving the applicability of peptide based MRM assays. These technologies, used with ultra-fast mass spectrometry save your laboratory time, money and resources and will greatly improve data reproducibility and quality. Lastly we will examine how cloud-based informatics solutions are simplifying laboratory data storage, automating entire-lab workflow processing and enabling global collaborations. |
Monitoring Dynamic Responses to the Gut Microbiota via Host-centric Proteomics of Stool
Josh Lichtman, Dept. of Chemical & Systems Biology, Stanford University Medical Center
| The diverse community of microbes that inhabits the human bowel is vitally important to human health. Host-expressed proteins are essential for maintaining this mutualistic relationship and serve as reporters on the status of host-microbiota interactions. However, the identities and regulation of these proteins are poorly understood. Therefore, we have developed an unbiased, non-invasive and sensitive method focused on host proteome characterization. Applying this method to extensively characterize the healthy mouse gut, we have discerned dynamic and temporal responses to commensal microbes. We have gone on to use a mouse model of Salmonella typhimurium infection to elucidate host responses during pathogenesis of antibiotic-associated disease. From these analyses, a deeper understanding of mutual host-microbe interactions is beginning to emerge. |
