THEME 1 MOLECULAR MOVIES USING XFEL

‘Molecular Movie’ Reveals Ultrafast Chemistry in Motion: This illustration shows shape changes that occur in quadrillionths-of-a-second intervals in a ring-shaped molecule that was broken open by light. The molecular motion was measured using SLAC’s Linac Coherent Light Source X-ray laser. The coloured chart shows a theoretical model of molecular changes that syncs well with the actual results. The squares in the background represent panels in an LCLS X-ray detector.

Image: SLAC National Accelerator Laboratory

“We have now developed a new platform to control and measure molecular dynamics in real-time at the atomic scale. This will provide unpresented insight into the inner workings of biomolecules.”

Working with the Australian Synchrotron and the Melbourne Centre for Nanofabrciation (MCN), we have developed new approaches for chemically ‘triggering’ molecular movies using state-of-the -art nanofabrication techniques. This technique is being deployed at the XFEL and will allow us to capture the real-time dynamics of biomolecules on sub-picosecond timescales.

Photo of Professors Brian Abbey and Keith Nugent

A/PROF. BRIAN ABBEY
PROF. KEITH NUGENT

AT A GLANCE

The ability to collect high-resolution, damage-free, molecular movie data at atomic resolution is fast becoming a reality thanks to recent availability of XFELs. Conventional synchrotron and electron-based techniques typically provide a static view of molecular structures. Through a process known as ‘diffract-and-destroy’ XFELs are able to take snapshots of molecular conformations prior to any significant nuclear motion occurring.

One of the major challenges with XFEL based molecular movies is the amount of data required to enable a 3D reconstruction of the relevant molecular dynamics. In December 2017 the worlds’ first MHz XFEL source, the European XFEL, came online. These sources can collect orders of magnitude more data then current generation XFELs potentially solving one of the biggest problems faced by groups making these types of measurements.

Imaging CoE researchers were part of the first group in the world, and the only scientists from Australia, to use the European XFEL to collect atomic resolution data from proteins. Over the past 12 months this data has been successfully analysed to produce the worlds’ first MHz X-ray structures (Wiedorn et al. Nature Comm. 2018 and Grünbein et al., Nature Comm. 2018). This result is a significant boost to efforts in generating real-time, atomic-scale molecular movies using XFELs and paves the way for Centre researchers to apply this approach to studying biomolecules. This work was also highlighted in the Herald Sun newspaper.

However, with the much faster data rates, issues around how to handle and process the more than 30,000 frames of data collected each second, become even more critical. Jointly supported by ANSTO, Imaging CoE researcher Dr Marjan Hadian has been developing algorithms for online processing of XFEL data. Her work is currently being integrated into the data analysis pipeline at the European XFEL and will benefit both Australian researchers and the international molecular movies community.

Other recent successes include the commercialisation of the La Trobe groups’ molecular imaging technology as a platform for ultra-sensitive tissue imaging. In 2018 the team behind this technology won several regional and national awards (including being finalists in the Medtech’s Got Talent awards) and were successful in attracting significant support to help with commercial development.

ACTIVITY PLAN

  1. Work with the Australian Synchrotron and the external user community on the serial synchrotron crystallography (SSX) platform built by La Trobe University and Monash University at the MX2 beamline.
  2. Analyse the molecular movies data collected from key regulators of the complement system at the Australian Synchrotron.
  3. Continue to develop new approaches to extracting structural information from XFEL SAXS/WAXS data based on LCLS experiments performed in September 2018.
  4. In collaboration with the theoretical physics group at University of Melbourne and Bio21 continue to work on understanding the effects of confinement in single particle imaging experiments.
  5. Continue the commercialisation of our imaging technology with a view to forming a company in 2019.

HIGHLIGHT

The secret life of atoms

In 2018 the first protein structures measured using MHz XFEL sources were published. These experiments paved the way to performing molecular movies experiments in real-time at the atomic scale where data volumes and sample consumption are major challenges which need to be addressed. Our molecular movies program is designing methods for triggering molecular movies as well as new approaches to analysing big data and interpreting XFEL diffraction patterns.

“This is innovative science and arguably the biggest science project in the world right now,” La Trobe University researcher Professor Keith Nugent said.

“It’s exciting for our team to work alongside the world’s best molecular scientists, as well as a number of our students who are now based at Euro XFEL.”

La Trobe University’s A/Professor Brian Abbey, Chief Investigator of the Imaging CoE, said the laser “allows, for the first time, snapshots of the atomic structure of molecules to be captured at a rate of up to one million images per second, allowing us to track their movements and interactions in real-time”.

“This information can be used to construct 3D models of proteins as they change their shape in solution or come together and combine to form larger structures,” A/Professor Abbey said.

Rapid mix-and-inject device for creating biological movies at the XFEL designed and fabricated by the La Trobe CoE node. From: Hejazian et al. Microfluidic mixing and jetting devices based on SU8 and glass for time-resolved molecular imaging experiments. SPIE, 2019 (in-press).

ACHIEVEMENT

Commercialising imaging technology

During 2018, Chief Investigator A/Professor Brian Abbey and CoE nanofabrication expert Dr Eugeniu Balaur worked towards commercialising a new type of ultrasensitive imaging technology for characterising tissues. Initially developed as a way to track molecular dynamics in-situ their breakthrough enables stain-free, label-free, imaging of optically transparent samples providing a new approach to understanding and detecting disease.

Following a series of laboratory trials, the La Trobe group have been successful in attracting significant financial support for commercialisation of their technology and are currently working on establishing a spin-out company based on their patented devices.

The La Trobe node have won multiple awards for their technology over the past 12 months including a 2018 regional innovation award; they are also finalists in the Medtech’s Got Talent program which aims to support new start-ups form long term sustainable businesses within Australia.

La Trobe University researchers were finalists in the 2018 Medtech’s Got Talent award picking up a $10,000 prize. From L-R, Imaging CoE researcher Dr Eugeniu Balaur, La Trobe Senior Commercialisation Officer Dr Caroline Bathje, Chief Investigator A/Prof Brian Abbey, and Dr Richard Stevens business development manager at Hydrix.