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Research Update: the ACRF Detector

THE GRANT

In 2015 ACRF awarded $2 million to The Australian Synchrotron. The ACRF Detector funded would enable the shape and function of proteins to be analysed on the Australian Synchrotron’s Micro Crystallography (MX2) beamline in a fraction of the time taken, providing a ten-fold increase in capacity crucial to accelerating cancer drug development.

The capital investment was used  to significantly expand the capability of the Australian Synchrotron Micro Crystallography (MX2) beamline. This technology accurately analyses the 3D shape and functional interaction of proteins. 

The brilliant light of the MX2 beamline allows researchers to investigate the arrangement and activity of molecules in cancer cells (and cancer treatments) at a level of detail that is not possible at any other Australian research facility. 

By introducing the capacity to process large numbers of micron sized protein crystals, the ACRF Detector increases capacity of this crucial beamline, enabling many more research studies to take place, while producing data of greater accuracy and quality. 

This means researchers will gain answers much faster, shortening the time from laboratory research to the clinical trial, which tests the performance of new cancer drugs. 

The grant was awarded to an esteemed research consortium comprising of micro-crystallography experts from six research institutions across Australia. The ACRF Synchrotron became operational in 2016. 

At the time the ACRF investment in this key cancer research technology, was available at only a handful of other synchrotron facilities around the world.

Dr Rachel Williamson with the ACRF detector on the MX2 beamline.

PROGRESS in 2019

The ARCF Eiger 16M Detector has been revolutionary for the MX2 Beamline at the Australian Synchrotron. From an operational perspective, 2019 saw the detector collect 51,064,846 diffraction images, associated with 71,460 datasets across 240 distinct group experiments. Approximately 5 petabytes of raw (uncompressed) data were generated by the ACRF detector in 2019 prior to reduction, processing and analysis.

Use of the ACRF Detector on the Micro-Crystallography (MX2) beamline has continued to grow, and the Macromolecular Crystallography beamlines at the Australian Synchrotron (MX1 and MX2) produced a record number of publications in 2019. More than 210 peer-reviewed scientific journal articles were published in the highest quality journals such as Science, Nature Immunology, Nature Cell Biology, Trends in Biochemical Sciences and Science Translational Medicine.

Large numbers of protein structures from the Australian Synchrotron (~290) were also deposited in the worldwide Protein Data Bank (PDB). Scientific outputs from the MX2 beamline and the ACRF Detector have increased compared to 2018, with 89 PDB structures and 60 journal publications based on data acquired using the ACRF Detector.

In 2019 one of the applicants for the grant for the ACRF Detector (Peter Czabotar from the Walter and Eliza Hall Institute for Medical Research) received the Prime Minister’s Prize for Innovation. Dr Czabotar has also been a productive user of the ACRF Detector during the year, with a publication resulting from use of the detector appearing in the journal Nature Communications.

The Australian Synchrotron has continued to deliver excellent science outputs and outcomes in 2019. This is evidenced by a record number of 608 peer-reviewed journal publications resulting from research undertaken at the facility. Over 1/3 of these publications (214) resulted from structures determined using the MX1 and MX2 beamlines, demonstrating the importance of these beamlines to the scientific program at the Australian Synchrotron. The number of journal articles published in 2019 that contain data taken using the ACRF Detector continues to increase in line with expectations based on the lead-time between data collection and publication. Starting with 4 publications in 2017, there were 311 in 2018 and more than 60 in 2019. Over the next few years we will see continued growth to the point where almost all MX2 publications (which account for the majority of publications on MX1 and MX2) will result from data collected using the ACRF Detector. 

2019 saw at-least 88 research theses published containing results from Australian Synchrotron beamlines; the vast majority being for Doctoral Theses. This is a substantial underestimate of the actual total number of research theses, which usually numbers more than 150 per annum. More than 1/3 of these research theses contain data from the MX1 and/or the MX2 beamlines. The Australian Synchrotron StephenWilkinsThesisMedalfor the most outstanding doctoral thesis in 2019 was awarded to Dr Angus Cowan (WEHI) for his thesis: Structural Investigations of Pro-apoptotic Bcl-2 Family Proteins. This research was centrally focused on understanding key biomolecular mechanisms associated with cancer and cell death, with his work also contributing to the development of the drug Venetoclax.

Read the full report here