The Selby Research Awards are granted annually by both the The University of Melbourne and The University of Sydney. The award is to assist an outstanding academic establish his or her research career. The Foundation congratulates:

• Dr Christopher Hall, School of Chemistry, University of Melbourne
• Dr Ben Fulcher, School of Physics , University of Sydney
• Dr Xuyu Liu , School of Physics , University of Sydney

Dr Christopher Hall

School of Chemistry
University of Melbourne
Awarded on 30/12/2022

Research project title: Probing drug-target interactions under physiological conditions

I’m interested in the development of new ultrafast spectroscopic techniques to extract information on fundamental interactions that determine the efficiency and functionality of materials. In doing so I seek to profoundly enhance our understanding of energy and chemical conversion in complex systems and to reveal design targets for their optimisation. I have employed these techniques to better understand light controlled biochemical reactions and signalling pathways in proteins, excited-state reactions and dynamics in engineered molecular systems and molecular-machines, as well as properties and interactions in semiconductors.

The primary tool for studying reaction pathways in photochemical systems is ultrafast laser spectroscopy, where short laser pulses ~100 femtoseconds in duration are used to resolve fast electronic and molecular-level structural changes. Despite 30 years of progress developing these techniques, separating and quantifying competing reactions in remains a major challenge in many systems.

My research has the potential to support the development of cheap and efficient materials for advanced future solar technologies, the development of light-activated proteins as tools in biological research, the development of nanoscale molecular machines with the potential to manipulate nanoscale interactions, and the potential to better understand how drugs bind and interact with target sites under real world conditions.

This project seeks to develop a new technique for probing drug structure and bonding at a target site under physiological conditions utilising femtosecond duration (ie. ultrafast) infrared laser pulses. This work addresses one of the main challenges in the development of new pharmaceuticals: obtaining experimental information on bonding and structure under conditions where pharmaceuticals are required to be effective (i.e. in solution at body temperature).

To achieve this goal this project has multiple objectives. Firstly, we aim to design and test a dedicated facility to excite and probe selected vibrational modes of a protein-bound drug molecule. While our lab is already has the ability to generate infrared pulses from a single light source, this project requires two synchronised and spectrally tuneable infrared pulsed laser sources. With the optical components purchased through the Selby Award, we will be able to build an instrument to provide a second source of infrared pulses.

With two light sources, we can selectively excite and probe vibrational modes in these drug-protein systems, providing direct insight into molecular structure and bonding localised at the binding site. We aim to demonstrate these capabilities by application to DNA binding pharmaceuticals, similar to pharmaceuticals used in chemotherapy.

Personal motivations

Over my career I have had the opportunity to pursue research over a broad range of topics within the disciplines of chemistry, physics and biology. Ultrafast spectroscopy is predominantly used in the area of energy materials research, however, I have been continuously drawn to the development and application of advanced laser spectroscopy techniques to problems outside of energy materials research owing to their ability to probe fundamental processes.

These techniques have great potential for application to biological problems, but to date few people have made the leap, likely owing to the knowledge gap in working with biologically oriented

 

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Dr Ben Fulcher

School of Physics
University of Sydney
Awarded on 01/03/2022

Senior Lecturer, School of Physics

Ben completed a Bachelor of Science (Adv) (Hons) at the University of Sydney in 2007, and a Master of Science (Physics) in 2008 on the topic of physiologically based modeling of sleep-wake dynamics.

He later graduated with a Doctor of Philosophy at the University of Oxford in 2012, with a focus on time-series analysis and machine learning. He worked as an NHMRC early- career researcher at Monash University from 2013-2017 on computational neuroscience, involving patterns of brain connectivity and gene expression. He has been with the School of Physics at the Unversity of Sydney since November 2017.

Ben leads the Dynamics and Neural Systems Groups in the School of Physics. His research interests are broad, spanning time-series analysis, information theory, machine learning, and systems neuroscience. Broadly, he uses methods from statistics and physics to quantify and explain the dynamics of complex systems like the brain, with the ultimate aim of understanding principles of brain function in terms of physical mechanisms of information processing.

Message of thanks

“I wanted to write to express my appreciation for your support of my research. I felt overjoyed and extremely grateful to receive the Selby Research Award. Support in academic research is hard to come by, and this means a lot for me as I try to build a supportive and world-class research lab at an early stage in my career. The funding improved both the quality of my research (through supporting travel to visit with cutting-edge collaborators) and its reach (through support of travel to present our work at conferences).

Our group works across two main areas:

– Dynamics. We are working to develop new general analysis methods to understand the dynamics of complex systems, including feature-based time-series analysis, multivariate information dynamics, machine learning, and dimensionality reduction.

– Neural Systems. We work with experimentalists to develop and refine mathematical models of whole-brain activity dynamics, including how to obtain information about neural circuits (on the microscale) from measured population-level neural activity at the macroscale (eg. Using EEG or fMRI). Bridging this gap is key to using non-invasive neuroimaging tools to probe underlying neural architecture, a technology that, if realized, we be transformational for medical imaging. 

Perhaps most importantly, your support is very meaningful to the extremely talented young students in my research group — it made a big difference in supporting their growth into independent scientific thinkers, through opportunities to visit leaders in the field at conferences. I would like to express my sincere appreciate to the Foundation for their support.”

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Dr Xuyu Liu

School of Physics
University of Sydney
Awarded on 01/02/2023

Senior Lecturer, School of Chemistry

Dr Xuyu Liu is a Conjoint Senior Lecturer and ARC DECRA Fellow in the School of Chemistry and the Heart Research Institute within the University of Sydney.

Xuyu began his studies in biomedical science in New Zealand, before completing his doctoral training in the field of chemical biology under the supervision of Professor Richard Payne at the School of Chemistry, the University of Sydney, in 2017. His PhD study focused on developing new peptide ligation technologies to efficiently prepare bioactive peptide libraries for cardiovascular drug discovery. He subsequently took on the position of postdoctoral associate at Cornell University, and later the École Polytechnique Fédérale de Lausanne, Switzerland.

Xuyu’s research interests are in the areas of developing new chemical synthesis and proteomic platforms for precision medicine discovery. He works closely with cardiologists and haematologists at the Charles Perkins Centre and the Heart Research Institute, aiming to decipher clinical genetics to develop next-generation precision medicine.

Project synopsis

The objective of Xuyu’s project is to investigate how natural modifications of proteins impact protein function and cellular decision-making processes. To achieve this, the project will develop a synthetic platform for discovering novel tool molecules capable of precisely engineering proteins in living cells. This initiative is expected to generate new insights and expand knowledge in the fields of organic chemistry and chemical biology.

In particular, the molecules developed through this project will be used to investigate the functional consequences of protein ubiquitination modifications in platelet and neutrophil cells - two critical components of blood that are involved in thrombosis and stroke. Successful translation of this technology for cardiovascular research will potentially transform the way in which protein modifications are studied and pave a novel avenue to develop cardiovascular precision medicine.

Message of thanks

“The Selby Research Award is an excellent opportunity for early-career researchers to receive financial support to pursue their innovative ideas, providing them with the resources to build their capacity and generate high-impact data for competitive grant applications.

This award and other research grants offered by the Foundation demonstrate a dedication to promoting scientific research and innovation and investing in the future of science. I would like to express my gratitude to the Foundation and Mr Selby for their generous support in promoting research, innovation, and training in my laboratory.”

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