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Microfluidic bioimaging for monitoring protein phase behaviour in biological systems


   PhD Opportunities

   Applications accepted all year round  Funded PhD Project (Students Worldwide)

About the Project

Over the past decades, protein aggregation has been recognised as one of the causes of neurodegenerative disorders, such as Alzheimer’s disease. The initiation of this pathological aggregation is normally considered from the nucleation of protein monomers. However, it has become more apparent recently that proteins can first undergo a liquid-liquid phase separation (LLPS), forming condensates then a further liquid-to-solid translon (LST) forming irreversible aggregates, leading to diseases.

Despite the importance of the phase behaviour of protein complexes, very little tools can be used to probe them and determine their dynamics and mechanics. It is therefore urgent to develop a non-invasive advanced technique with the capability of micro-environment manipulation to study them.

Dr Yi Shen has developed a set of novel microfluidic assays to probe biomolecules and protein materials. She has developed a microfluidic approach to quantify the calcium dependent lysosome binding of proteins [Cell, 1, 147-164, (2019)] and designed a microfluidic device to induce the protein LLPS and trigger the LST with controlled pressure drop [Nature Nanotechnology 15, 841-847, (2020), featured on the cover]. She has further measured the mechanical properties of the condensates by modulating and detecting their deformation in tapered channels [Advanced Materials Interfaces, 8, 2101071,(2021)] [MRS Bulletin, accepted].

Leveraging on this prior work, this PhD project will focus on microfluidic integrated high-speed, high resolution and high sensitivity advanced imaging to achieve non-invasive, non-disruptive probing of protein complexes and soft materials in biological systems.

Applications and more information: Doctor of Philosophy (Engineering) - The University of Sydney

About the PI

Dr Yi Shen is a researcher within the University of Sydney’s School of Chemical and Biomolecular Engineering. Her research interests span biomolecular engineering to biophysics, with a focus on protein phase behaviour and functional biomaterials by exploiting a set of soft matter approaches and microfluidic techniques.

She has published 17 high quality papers, including 2 first-author papers published in Nature Nanotechnology, both featured as cover, 2 in Cell, 1 in Nature Communications, 1 in Advanced Materials and many other high impact journals. 


Funding Notes

The PhD position will be funded by faculty scholarship. We are looking for current final year Bachelor or Master students in Engineering, Physics or Chemistry with GPA > 80 (out of 100). Background of biophysics nanotechnology and soft matter will be appreciated but not limited.

References

Liao, Y.-C., Fernandopulle, M. S., Wang, G., Choi, H., Hao, L., Drerup, C. M., … Ward, M. E. (2019). RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether. Cell, 179(1), 147-164.e20.
Shen, Y., Ruggeri, F. S., Vigolo, D., Kamada, A., Qamar, S., Levin, A., … Knowles, T. P. J. (2020). Biomolecular condensates undergo a generic shear-mediated liquid-to-solid transition. Nature Nanotechnology, 15(10), 841–847.
Xu, Y., Zhu, H. V., Shen, Y.*, Gutternplan, A. P. M., Saar, K. L., Lu, Y., Vigolo, D., Itzhaki, L. S., Knowles, T. P. J. (2021) Micromechanics of soft materials using microfluidics. MRS Bulletin, accepted.
Xu, Y., Shen, Y., Michaels, T. C. T., Baumann, K. N., Vigolo, D., Peter, Q., … Knowles, T. P. J. (2021). Deformable and Robust Core–Shell Protein Microcapsules Templated by Liquid–Liquid Phase‐Separated Microdroplets. Advanced Materials Interfaces, 8(19) 2101071.

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