小中大对蛋白组学牛人的Ruedi Aebersold采访
Interview: Putting peptides on the map
18 February 2008
Ruedi Aebersold talks to Kathleen Too about proteomics, the PeptideAtlas project and the Trans-Proteomic Pipeline.
Ruedi Aebersold is professor of systems biology at the Swiss Federal Institute of Technology, Zürich, with a joint appointment at the University of Zürich's faculty of science. He is also one of the founders of the Institute for Systems Biology in Seattle. Ruedi is a pioneer in the field of quantitative proteomics and has developed a number of methods that have been widely applied in analytical protein chemistry. Ruedi is a former Molecular BioSystems editorial board member.
Why are you interested in systems biology and proteomics?
I have been working in the field of proteomics for a very long time. First, I learnt how to identify and characterise a single protein and then, through technical developments, I started looking at large numbers of proteins.
"Systems biology looks at the bigger picture"I am interested in systems biology because I wanted to learn how different systems work and how molecules relate to each other. Systems biology looks at the bigger picture.
Proteomics has got to the point where many protein interactions can be measured. This means there is a lot of useful information for system biologists coming out of proteomics.
What are the most exciting projects you are working on at the moment?
We are trying to find biomarkers that indicate certain diseases. Proteomics itself cannot heal a person but it does have the potential to have a sizeable impact in the pharmaceutical industry. I expect that in the next few years, biomarkers for disease classification will become available, allowing clinicians to detect diseases earlier and treat them more accurately.
Another interest of mine is protein kinases and phosphorylation. It is the most common way to regulate cellular activity. In essence, kinases put the phosphates on proteins and phosphatases take them off. We attempt to establish a relationship between these enzymes and their substrates and determine the functional consequences of protein phosphorylation.
What is the biggest challenge that systems biology should tackle in the near future?
Cancer and obesity need to be addressed. Our work is part of a larger project related to metabolic disease syndrome, partly funded by Roche Pharmaceuticals. The aim is to understand the basic repercussive circuits that lead to type II diabetes and obesity in humans. We work with a consortium of different clinicians and scientists to approach the problem in a more comprehensive way than is possible in a single research lab.
You are one of the founders of the PeptideAtlas project. Can you describe what this is?
"By collecting a community-generated dataset, we hope to get as close as possible to building a complete proteome map"The PeptideAtlas project is an attempt to unify in one database all the mass spectrometry-derived protein sequences from a particular species. Many laboratories are doing proteomics by mass spectrometry. They generate a huge amount of data but only use a small fraction of it. We use it to create an informatics database, from which we can learn many things. It tells you which proteins have been identified in any one experiment. It also allows you to start doing analyses of the data to see, for example, how many times has a particular peptide been seen in protein mass spectra. By collecting a community-generated dataset, we hope to get as close as possible to building a complete proteome map.
You were a member of Molecular BioSystems editorial board when it was first launched. What has been most exciting in the development of the journal?
"Molecular BioSystems has found its niche at the interface of chemistry, chemical biology and systems biology"What is really exciting is that it is a new journal in a new field. It is always nice to be there when a journal gets off the ground. There were a lot of interesting discussions about the name, the direction and orientation of the journal.
Molecular BioSystems has found its niche at the interface of chemistry, chemical biology and systems biology. That is a very important niche and I think that the journal has had a very good start and will do very well.
Which achievement are you most proud of?
We established a computer tool, called the Trans-Proteomic Pipeline, that estimates the percentage error in a dataset. Mass spectometry generates about ten thousand fragment ion spectra per hour. Computer programs match the fragment ion spectra back to a sequence. How do we know that the computer is correct? Many journals, including Molecular BioSystems, require that an estimate of error is given when scientists say that they have identified thousands of proteins. Our pipeline enables people to do this and has helped increase the quality of data generated.
The software has been downloaded thousands of times and is used in many laboratories. Also, some companies have taken these tools and put them into commercial suites. We have trained several hundred proteomics scientists in the use of the tools in intensive week-long courses.
If you went back into the lab, what experiment would you work on?
I think I would work on the relationship between protein kinase and disease because it is clearly important and now technically feasible. Unfortunately, this is highly hypothetical since I can hardly keep up with the other things that need to be done in the office.
