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 John Bartholomew, Centre for Engineered Quantum Systems, University of Sydney
• Dr Mark White , School of Chemistry, 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 John Bartholomew

Centre for Engineered Quantum Systems
University of Sydney
Awarded on 01/03/2022

“While still in its infancy, quantum technology is already eclipsing what is possible compared to the most powerful computers currently available. While the rate of quantum computing development is accelerating, new discoveries are now needed to deliver the all-important future networks connecting them. This project aims to create new photonic technologies that will advance the performance of the quantum internet and create opportunities for advanced sensing capabilities. These include:

– a novel high-performance optical filter designed to keep fragile quantum information separate from stray signals in an optical fibre; and

– a technique for quantum-enhanced optical astronomy, which will hopefully enable the imaging of details in the universe that were previously hidden. This will mean a better understanding of the formation of stars, planets, and our solar system.”

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Dr Mark White

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

“Oxygen (O₂) regulation is critical for mammalian life and can be impaired by many diseases due to inadequate blood flow. As a result, O₂ deprivation (hypoxia) contributes to some of the leading causes of death in developed countries, including stroke, ischemic heart disease, and cancer. 

Essential molecular mechanisms have evolved to maintain O₂ and coordinate appropriate changes to alleviate hypoxic strain, including the influential Hypoxia Inducible Factor (HIF) system. However, additional response networks have been identified with the potential to revolutionise our understanding of oxygen deprivation responses in ischemic diseases. One of the most prominent is the oxygen dependent branch of the N-degron pathway, which, through the 2-aminoethanethiol dioxygenase (ADO) gene, complements the output of HIF faster by directly influencing protein levels in response to hypoxia.

This project aims to:

– use a number of biochemical techniques to understand how ADO functions as an oxygen sensor;

– identify new substrates of the oxygen-dependent branch of the N-degron so that its role in hypoxic adaptation can be fully appreciated; and

– establish chemical modulators of ADO, which may be useful in the treatment of low oxygen disorders.” 

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