Only at ISB: Our Proteomics Journey

THEN

ISB was founded in 2000 by Dr. Lee Hood, a systems biologist; Dr. Alan Aderem, an immunologist; and Dr. Ruedi Aebersold (pictured below), a protein chemist. This dream team created a dynamic intersection of disciplines that pervades ISB today and continues to drive innovation in research, computation and technology.

Dr. Aebersold, who is currently a professor at the Institute for Molecular Systems Biology at the Swiss Federal Institute of Technology (ETH) in Zurich and is an ISB affiliate faculty member, established ISB’s leadership in the field of proteomics – the study of the full complement of proteins in organisms. While DNA as the blueprint of life is important to understand, it’s the proteins that comprise the tiny molecular machines doing the actual work of growing cells and controlling functions or causing dysfunctions.

ISB established a mass spectrometry lab as a core research component. Mass spec is the technology that identifies proteins in samples that are run through the machines. This core facility represents one of the aspects of systems biology as we pioneered it: that essential technologies are shared across the institute thereby allowing us to streamline the use of resources and encourage cross-disciplinary as well as inter-institution collaborations.

NOW

Dr. Robert Moritz joined ISB in mid 2008 as an associate professor and director of proteomics. Under his leadership, ISB has contributed even more to the field of proteomics. ISB currently has 20 mass spec machines in the lab, which is one of the largest in the West Coast region. With ongoing collaborations with Dr. Aebersold at ETH Zurich, our marquee project has been the development of the SRMAtlas (SRM stands for selected reaction monitoring; it’s also known as MRM or multiple reaction monitoring). The ISB-developed SRMAtlas is an open-access compendium of targeted proteomics assays (analysis procedures) that use mass spec to detect and quantify proteins. The comprehensiveness of the SRMAtlas has served to “democratize proteins” making it easier for more labs worldwide to conduct targeted experiments that don’t require specialized analysts – a bottleneck – and yield consistent results.

The movement toward targeted proteomics (quality and quantity) versus discovery proteomics (stochastic measurement) was named “Method of the Year” in the December 2012 issue of Nature Methods. Dr. Moritz and Dr. Aebersold were among a group of proponents highlighted in this special issue. This honor was followed by publications in the journals Nature and PNAS (Proceedings of the National Academy of Sciences).

The Nature paper, a collaboration between the Moritz and Aebersold groups at ISB and ETH Zurich, for the first time illustrated that targeted proteomics can provide Quantitative Trait Loci (QTL) measurements at the protein level to understand genetic variation from a large number of samples with high precision. The PNAS paper, a collaboration across five ISB faculty and affiliate faculty groups (Aitchison, Ranish, Shmulevich, Aebersold, Galitski), demonstrates the power of SRM (targeted proteomics) in studying gene regulation and as a new approach for the systematic measurement of protein-DNA interactions.

FUTURE

Because ISB scientists aren’t satisfied unless they’re pushing the edge of technology, we recently announced a strategic partnership with AB SCIEX, a US/Canadian-based company that produces some of the most advanced mass spec technology available on the market. ISB will collaborate to develop workflows, libraries, and data analysis and dissemination tools similar to the SRMAtlas effort for AB SCIEX’s SWATH technology, which offers the fastest, most sensitive and precise measurements for a mass spec instrument to enable truly comprehensive quantitative proteomic technology.

Because ISB subscribes to an open-access ethos, the methods and resources developed for this partnership will be available to all researchers. Having such standardized methods, data and analysis tools will enable more labs to adopt the latest proteomics technology. This technology helps to understand the molecular basis of diseases and eventually will lead to identifying biomarkers that can predict whether a patient will respond to a specific treatment or not.

– Published Feb. 13, 2013