A high-definition approach for quantitative experimental measurements of membrane protein mechanosensitivity

 

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This is one of two research projects on bioengineering. The University of Melbourne is the home institution for this project.

This project aims to develop a fundamentally new approach for the experimental investigation of an exciting and emerging class of mechanosensitive membrane proteins. These proteins are unique in that they embody a pathway for modulating neuron behaviour using sound rather than light. Inducing their targeted expression and then selectively activating them with sound in such a ‘sonogenetic’ approach represents a ground-breaking way to treat neurodegenerative diseases. Compared to optogenetics, this is significantly advantageous as even deep brain regions can be targeted for therapy entirely non-invasively. Before this achieves the widespread utility of optogenetics, however, fundamental work is required to characterise an evolving array of mechanically sensitive proteins. This characterization is predicated on the use of microfluidic devices and micro-actuation systems to probe and elicit responses in membrane-bound proteins in a unique experimental platform that will give fundamental insights into these proteins’ mechanisms. This is deeply exciting work that will be of interest to those with experience or a desire to work with microdevices, numerical simulation and microfabrication approaches.

Project goals

This project aims to develop a new approach for the mechanical measurement of membrane-bound proteins. This is particularly interesting in the context of mechanosensitive proteins, the understanding of which is fundamental for the developing field of sonogenetics. Stimulation-sensitive proteins, including those responsive to mechanical stimulation, are fundamental to how we perceive and interact with the world.

To achieve breakthroughs, we will deploy the following work plan:

  1. Microscale active devices to generate defined forces.
  2. Simulation models of microscale tension and stresses.
  3. Membrane Tension measurements of bound transmembrane proteins in GUVs.

Supervision team

The University of Melbourne: Dr David Collins

*Click on the researcher's name above to learn more about their publication and grant successes.

KU Leuven: Professor Xavier Casadevall i Solvas

Who we are looking for

We are seeking a PhD candidate with the following skills:

  1. Demonstrated experience in the field of biomedical engineering.
  2. Demonstrated experience with biometrics.
  3. Demonstrated ability to work independently and as part of a team.
  4. Demonstrated time and project management skills.
  5. Demonstrated ability to write research reports or other publications to a publishable standard (even if not published to date).
  6. Excellent written and oral communication skills.
  7. Demonstrated organisational skills, time management and ability to work to priorities.
  8. Demonstrated problem-solving abilities.

Further details

The PhD candidate will benefit from the combined expertise of the project supervisors, and the embedding into two research environments.

Dr David Collins and Professor Xavier Casadevall i Solvas will lead the research teams in UoM and KUL, respectively. Prof Casadevall i Solvas will provide expertise in artificial cell generation (for both topics) and activities related to the integration of biomimetic scaffolds. Professor Bart Smeets and Professor Jeroen Lammertyn will provide expertise and support from the KUL side in terms of membrane protein integration and dynamics in artificial cells and microdevices/microfluidics. Dr Collins will provide expertise in micro/nanofabrication of biomimetic scaffolds, the development of acoustic microdevices, and numerical simulation. Professor Daniel Scott and Professor Michael Parker will provide support from the UoM side in the form of expertise in mechanosensitive and pore-forming membrane proteins, respectively.

This PhD project will be based at the University of Melbourne with a minimum 12-month stay at the KU Leuven.

The candidate will be enrolled in the PhD program at the School of Chemical and Biomedical Engineering at the University of Melbourne and in the PhD program at the Faculty of Bioscience Engineering/Biosystems at KU Leuven.

To apply for this joint PhD opportunity, and to view the entry requirements, visit How to apply.

First published on 1 February 2022.

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