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UK Researchers Explore Platforms for New Proteomics Uses

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David Klug
Chair, Single Cell Proteomics project
Imperial
College London
Name: David Klug
 
Position: Chair, Single Cell Proteomics project; chair, Chemical Biology Center; professor of chemical biophysics, department of chemistry, Imperial College London, 2001 to present
 
Background: Reader, chemical biophysics, department of chemistry, Imperial College London, 1999 to 2001; PhD, physical chemistry, Royal Institution of Great Britain/UCL 1987; postdoc, Imperial College London, 1987 to 1990
 

 
During the summer the Energy and Physical Sciences Research Council in the UK provided £5 million ($9.8 million) to fund the Single Cell Proteomics and Lipidomics project to analyze and measure proteins found in cells.
 
The project is currently developing six technology platforms to carry out its research: tools for microfluidic separation; multidimensional coherent spectroscopers; single molecule spectroscopers; multidimensional fluorescence imagers; tools for selective membrane digestion and manipulation; and instruments for optical trapping.
 
David Klug is leading the effort. Following is an edited version of a conversation ProteoMonitor recently had with Klug.
 
How did [the Single Cell Proteomics and Lipidomics] project get started?
 
This basically is a big project run by the Chemical Biology Center. The Chemical Biology Center essentially stimulates and supports work at the life science, physical science interface with respect to biological problems of a molecular nature.
 
So this project emerged from various discussions from various people at the center. One of the things we realized is that we have a fairly unique mix of potential platform technologies either being developed or under development at Imperial College. This came from discussions within the center and actually getting to know each other.
 
So, it emerged over a few years of discussions, and the idea of the Single Cell Proteomics [and Lipidomics] project was to bring some of these platform technologies together in new ways and new combinations and new permutations to see what added benefit we could get by combining them these different ways. And then taking what we learned and applying it to some real biological problems.
 
How did you get involved in the project?
 
I’ve worked on various biological problems for a while. I’ve also developed a lot of instrumentation. We do a lot of laser spectroscopy, and partly through chairing the meetings of the center, we became aware of just how many synergies there might be, and [began] thinking about how they might apply to the problems I’m particularly interested in.
 
Like what?
 
I’ve done a lot of work on photosynthetic systems and we have a project on protein folding and actin folding.
 
You said there are a number of different platforms being developed or [that] exist already at the center. What are they?
 
We’ve grouped them in the following way. One of them is optical trapping, and I’ve done physical manipulation using optical fields. Another is multidimensional fluorescence imaging and extensions of that. Then we have strong microfluidics activity here. We have a lot of people who are experts at chemical manipulation of liquid membranes. And finally, we have strong spectroscopy, in particular, two-dimensional coherent optical spectroscopy for protein fingerprinting.
 
So there are versions of these already in existence, but the remit of the project is to firstly, develop them further in a particular set of directions, and to bring them together in various combinations and permutations so they can be used in various ways to get various end results in combination.
 
Appropriate in this context means they can fit together, so we can benefit from a maximum degree of synergy, and of course tailor it toward biological problems in the end. It’s a little early to be tackling real biology issues yet because we’re only six months into the project.
 
It’s early days, but we have a team here and it’s up and running and we’re doing research.
 
Ultimately, what’s the goal of this project?
 
If you want an unreachable fantasy goal — which is a good thing to have, I think — the unreachable fantasy goal is to be able to do the full proteomics on a single cell. We want to get as close to that capability as possible. And, of course, a lot of the things you can do with high sensitivity can be reformatted in a high-throughput way potentially.
 
One of the potential off-shoots might be high-throughput, lower sensitivity versions.
 
How novel are these platforms and the use of them for proteomics research?
 
I wouldn’t say there’s tremendous novelty in any one, though there are novel things in each of them. There are bits in each of them which are unique to the groups doing them. But I would say it’s the combination that’s the most interesting and important thing. It’s the synergies between them by bringing these things together, the added value, the added capability of that that’s important, rather than any one stand-alone capability.
 
Are you looking at any sort of diseases specifically?
 
The guys at the moment [who are] most heavily involved in the project do have a cancer background on the biological side. Once we have these platforms going, we do hope to open it out toward other problems, but you can imagine this being used in a number of diseases, but one of them is cancer stem cells. You can see it might have some potential there.
 
The platforms should be applicable, in principle, to a wide range of disease states or biological problems, though we’re focused on mammalian systems. We’re not really looking, at the moment, at bacterial systems, for example. But I guess it could be tuned in that direction.
 
Are you developing these platforms to identify proteins, or to quantify them?
 
Yes, all of that. I don’t want to be too specific. It’s early days and we’re still just getting momentum, getting going.
 
How’s your research different, then, from all the other proteomics research and technology development that’s going on?
 
I’m sure that you’ll find elements of this in a lot of places. So I think if you choose any one bit, you’ll find them replicated in a lot of places. I have not yet been able to identify anywhere that quite brings all of these together in all of these ways. This is a fairly focused effort. This is a team of about 12 people all working collectively as a single group. It’s not run as one guy over here, one guy over there. They’re all sharing offices, sharing facilities. It’s a real research team in its own right.
 
What have you done in the six months since this project was started?
 
Well, getting together a good team … [and] getting the labs up and going. At this point, there’s nothing we can tell you because we’ve not published anything yet. We’re starting to get data, we’re starting to get results. I don’t expect to go public with anything for another six months.
 
Can you give some idea what you’re looking at? When you say you’re starting to get some data, data on what?
 
We have cells and devices and we’re doing things with them. I’m not going to be any more specific than that. We expect to get results of a number of different types. Some results will really be about the development of the technologies in certain ways. And there will be others where those have been combined together in unusual ways. And there’ll be others where we’re starting to learn something about biology.
 
Is this the first project from the center looking at proteomics?
 
Yes, it is.
 
Why did the center decide to explore this discipline now?
 
I think the way to think about it is, it emerged from discussions. The purpose of the center, to a large extent, is to catalyze and encourage work across the disciplines, and so we organize a lot of discussions and talks and meetings. And the students are at least jointly supervised, and that provides extra glue between groups.
 
And we’ve had a number of projects that have emerged from this kind of activity, through that sort of multi-disciplinary way of working in which often the students often get catalyzed. New thoughts and then grants appear and projects appear from that.
 
And I think this emerged in just the same way. We realized that there were some problems in cell biology and biochemistry that weren’t easily tractable with existing methods.
 
The existing methods are powerful but not perfect, and we realized combinations of our approaches potentially could fill some of these gaps or even allow people [to do] things they haven’t thought of before. Undoubtedly, some of these approaches will not be very successful, and some will be mildly successful. And, hopefully, some of them will be very successful.

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