COE ARC beamline end-station development

Introduction
The majority of drugs on the market today (70%) rely on the activity of membrane proteins for their efficacy. Yet the structure of many of these proteins is currently unknown. The technique usually applied in structural biology - protein crystallography - requires that a crystal be formed and membrane proteins are steadfastly resistant to crystallisation. The principal aim of this project is to develop non-crystallographic techniques for the determination of membrane protein structures. However, we will use the long-term strategic goal of the determination of the structure of membrane proteins to articulate a plan that can be implemented using the Australian Synchrotron.

To achieve these goals, our part in this program will focus on the creation of a flexible experimental end station suited to the non-crystalline diffraction techniques under development.

Project aims
We will develop instrumentation to equip a suitable end-station on an in-vacuum undulator beamline at the Australian Synchrotron. The new methods to be developed by theoretical and modelling programmes will place significant technical demands upon both the optical and detector systems.

The key requirements for the end-station comprise a robust optical system designed to deliver the optimum coherent flux to the sample combined with the highest dynamic range detection system possible. The full needs for many areas of the beamline can be determined very quickly. We have identified candidate beamlines from the initial suite for the Australian Synchrotron that are near to our requirements. This will avoid development of a completely new and expensive beamline.

The optical systems will be based upon those at other major synchrotrons such as the ESRF and SPring8 but the detector system represents the greatest challenge. The detailed requirements of the detector system will require input from all aspects of the Centre's programs, but the key issue will be the ability to resolve the diffracted signal. Consequently, the main requirement on this system will be a spatially resolving detector with the optimum quantum efficiency, but primarily the highest possible dynamic range.

Collaboration
Our partners at the Singapore Synchrotron Light Source (SSLS) are pursuing a program of development of very high brightness undulators for protein crystallography applications, as well as planning a free electron laser development project. In the long term, as the relationship between Australia and Singapore develops, the Centre will nucleate a partnership in state-of-the-art structural biology methods leading ultimately to a fourth generation x-ray source. In the medium term, we anticipate that Singapore may place the Centre end-station developed by this program on a beamline constructed around the new "supramini" undulators being developed at the SSLS. This is a facility that our Singapore partners are proposing to incorporate into the suite of beamlines at the Australian Synchrotron.