TIME OUT - VICTOR LAMZIN: "Structural genomics can be pushed much further"

VICTOR LAMZIN, Deputy head of the EMBL Hamburg outstation and coordinator of BIOXHIT

By Montserrat Capellas

BIOXHIT is one of 15 EU projects funded under FP6 in which the ESRF participates. The aim of BIOXHIT is to develop, assemble and create an integrated platform for high-throughput structure determination of biological macromolecules with synchrotron radiation. Within the frame of BIOXHIT, the ESRF and all other European synchrotron radiation facilities are participating in the technology and software developments necessary to create high-throughput data collection platforms. The joint efforts of the staff from the ESRF and the EMBL-Grenoble outstation that has led to the successful automation of the seven end-stations dedicated to macromolecular crystallography comprise a significant contribution to the BIOXHIT project. The 2nd annual BIOXHIT meeting held at the ESRF in January 2006, gave the other partners and the external reviewers the opportunity to see at first hand the advances at the ESRF beamlines. An important aspect of BIOXHIT is the coordination of the automation efforts between the different European synchtrotrons, so a macromolecular crystallographer can mount crystals without thinking about which synchrotron will be used for data collection.

The use of synchrotron radiation has revolutionised structural biology, the effect is clearly demonstrated in the growth of the macromolecular structural data available in the Protein Data Bank. Out of over 35,000 structures in the bank, 75% has been determined based on synchrotron radiation data. Among the European synchrotrons the ESRF holds by far the leading position, with almost 3,000 structures in the PSB are based on data measured at the ESRF. Victor Lamzin from the EMBL-Hamburg outstation is the coordinator of the BIOXHIT project that tries to make the link between synchrotron sources and protein crystallography even stronger.

How did you come up with the idea of doing a project like this?
We started thinking about this back in 2001, when we realised that high-throughput technologies in structural biology were about to emerge. The number of synchrotron radiation facilities was growing and the required software was rapidly being developed but a consorted effort at a pan-European level was missing. In order for the project to materialise, however, it proved essential that the need for such effort should be appreciated by the funding agencies.

Was there any precedent?
The interest in structural genomics emerged much earlier in the US. From initial attempts to collect the so-called "fold space" of the molecules, the natural step was made towards the desire to understand the function of biological macromolecules. Very quickly it became apparent that structural genomics can be pushed much further if the required technology development is there at the same time. That is why the BIOXHIT project in Europe was started with coordination of methodology development - the software, hardware, data management - and to do that we brought together people from the 20 different partners representing nine European countries.

Having partners from all over Europe, doesn't their coordination seem a very challenging task?
The key word is "standards". Having a common user-environment for macromolecular crystallography in all European synchrotron facilities is a must and it is in the interest of both users and operators. What do you do when you want to drive a car? You always manage it, even if you change cars, they all have standard features (a wheel, a gas pedal, a windscreen in front, etc.). Why should biological crystallography with synchrotron radiation be more difficult?

How many people does this work involve?
Over 200 people from the European research community are involved in the project in active exchange of information and resource sharing. BIOXHIT also has a unique training programme and young groups from Poland and Finland are already benefiting from it.

Due to the importance that synchrotron sources are getting, will they be saturated with crystallographers in the future?
I strongly believe that the demand is driven by the offer. Some years ago there were only a few synchrotron beamlines suited for macromolecular crystallography and they were fully used. Now dozens of beamlines are also working day and night, not just for more projects but for more challenging experiments, some of which were not feasible before.

What are the advances that BIOXHIT will bring?
One example is the aim to change the way experiments are carried out at synchrotron sources. Currently one may try a large number of samples with only very few giving valuable data. Researchers should be able to bring or courier many different samples and evaluate them in one go. This would not only let them save time but also increase the throughput in terms of the amount of interpretable data. The increase in the quantity will one day advance the quality.

How will crystallographers use synchrotrons in the future?
We should be able to resolve the structures with minimum or even no human intervention. But we will not stop there and one day we may find it feasible to solve the molecular structure of a cell, not necessarily in a crystal the way we do it now.

Is BIOXHIT going to last for a long time?
We have funding for 4 years since we started, until December 2007, with a total budget of 10 million euros. I don't know whether there will be BIOXHIT-2 or something named differently, but I am certain that efforts like this project at this scale will definitely continue.