Single-molecule bioscience with nanostructured photonic device

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Join a world-leading, cross-continental research team

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The University of Exeter and the University of Queensland are seeking exceptional students to join a world-leading, cross-continental research team tackling major challenges facing the world’s population in global sustainability and wellbeing as part of the QUEX Institute. The joint PhD programme provides a fantastic opportunity for the most talented doctoral students to work closely with world-class research groups and benefit from the combined expertise and facilities offered at the two institutions, with a lead supervisor within each university. This prestigious programme provides full tuition fees, stipend, travel funds and research training support grants to the successful applicants.  The studentship provides funding for up to 42 months (3.5 years).

Eight generous, fully-funded studentships are available for the best applicants, four offered by the University of Exeter and four by the University of Queensland. This select group will spend at least one year at each University and will graduate with a joint degree from the University of Exeter and the University of Queensland.

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Project Description

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Cells are the building blocks of life. They are governed by nanoscale molecular machines. However, these machines are generally too small and their motion too fast to observe with existing microscopes. As a consequence, we have hardly scratched the surface of understanding how they work. This project will pioneer a new approach to resolve this problem by developing single-molecule senors that fit inside the cell. The sensor is based on nanoscale optical cavities fabricated on a miniature silicon chip which is biocompatible. This will allow molecular machines and their dynamics to be tracked inside the cell, noninvasively at their natural time and length scales, providing a disruptive new technology for the biosciences and biotechnology industry.

A detailed understanding of molecular dynamics underpins much of biotechnology, including the design of pharmaceuticals, chemicals, soft materials and artificial biomaterials, and targeted treatments for cancers and neurodegenerative diseases. Our new technology will stimulate significant new lines of discovery by allowing observation of single-molecule processes and dynamics in vivo, and in cases where computer simulations break down and there is scarce non-invasive experimental data. This project will provide new insights into grand challenges in biochemistry, including how nanomachines are designed and function in their complex in vivo environments, how proteins fold inside cells and how enzymes efficiently catalyse reactions in a crowded cellullar environment; with enzyme catalysis being critical to future energy technologies and misfolding linked to many debilitating diseases. We propose to develop an instrument to probe single molecules and proteins in vivo, inside the cell, in a specific and sensitive manner, while disturbing the cell as little as possible. The vision is to create a  precise in vivo probe for molecules that can characterise an arbitrary protein and its dynamics in the context of the living cell, a technology that is beyond the current state-of-the-art. Realising this in-vivo, single-cell-single-molecule sensor will lead to a new fundamental understanding of how the machinery of life functions. The micro-optical sensor will allow us to analyse proteins in entirely new ways by observing them at physiological condidtions in the cell. We will be able to study proteins specifically on micron-sized laboratories.   Our sensor platform will be able to contribute to the development of artificial molecular machinery by providing laboratory test beds that observe the motions of nano-machines in real time and in relevant biological environments. We will realise this instrument with optical nanocavity sensors. The microcavity sensors enhance the single-molecule detection signals by concentrating light at the nanoscale where they probe single proteins. We aim to intersect the nanoscale light field with a single protein to provide information on the protein structure and its dynamics, inside single cells, resolving protein motions and vibrations at a temporal scale of micro/nanoseconds and at a spatial scale of single bonds and atoms.

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The project will leverage recent multi-million dollar investments in state-of-the-art nanolithography at the University of Queensland (Prof Warwick Bowen), together with Exeter University's GBP52m investment into the Living Systems Institute where the single-molecule sensors will be applied to proteins and protein nanomachines (Prof Frank Vollmer), in ideal inderdisciplinary setting that brings together physicists, engineers and biologists to work side by side. It will combine the expertise of two world leading laboratories spanning precision photonics, biophysics and biomedical science, and bring together three major research initiatives, the UKRI funded Exeter Molecular Mechanics Initiatve, Australian Centre for Engineered Quantum Systems, and the Australian Institute for Bioengineering and Nanotechnology.

References: Light: Science & Applications volume 10, Article number: 42 (2021): Review of Whispering-Gallery Mode Lasers for Biosensing

Review of biosensing with whispering-gallery mode lasers | Light: Science & Applications (nature.com)

 

Please contact Prof Frank Vollmer for further information: f.vollmer@exeter.ac.uk

 

Please apply by May 24 here: Award details | Funding for prospective students | University of Exeter

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