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Tracking the motion of single nanoparticles inside living cells: New insights into intracellular crowdedness


Project Description

EPSRC funded DTP PhD Studentship within the Interdisciplinary Doctoral Training Hub “Physics of Life”

The Hub is designed as a cross-disciplinary PhD research and training programme at the physics/life science interface. Students will benefit from joint supervision across the Colleges of Physical Sciences and Life Sciences at Cardiff University. Each project commences with two 3-months stages in the labs of the joint supervisors. The Hub will offer cohort development opportunities through joint research meetings, a “Physics of Life” summer school in 2022, and a student-led workshop in 2023. Students will be part of a vibrant, interactive community, sharing monthly newsletters and connected via a dedicated portal. Each student will be supported by a mentor. The Physics of Life Doctoral Training Hub aims to equip PhD candidates with multidisciplinary research skills that are highly sought after in academic and industry.

How biomolecules move inside living cells, in space and time, is not only a fundamental research question but is key to the understanding of many biological processes. With the development of advanced single-particle tracking techniques, it has become apparent that biomolecules inside cells exhibit complicated types of motion, which cannot be simply described as random from thermal diffusion or directed motion via molecular motors. This is because the cell contains a cytoplasm crowded with large biomolecules and organelles, and a heterogeneous network of cytoskeletal protein filaments.

Key to the in depth understanding of biomolecular motion inside living cells is the development of new techniques capable to track single particles in 3D with high localisation precision and speed, alongside mathematical models that can describe the experiments according to physics’ law, and eventually reveal new insights into the highly complex living cell’s interior.

In this project, you will apply an advanced laser micro-spectroscopy technique called resonant Four-Wave Mixing, pioneered by the supervisory team, to image and track single small gold nanoparticles background free inside cells with precision at the nanoscale in 3D. Nanoparticles will be micro-injected into eggs (oocytes). These are large cells actively studied by the supervisory team (from mammals and invertebrates). They have ATP levels and metabolic rates closely linked to their ability to mature, be fertilised, and further develop into good quality embryos. Notably, movement of particles can be influenced by molecular motors that are ATP-driven. Hence, studies of intracellular motion in these cells will be a platform for new technologies to monitor embryo metabolism and predict viability.

Experimental single particle trajectories will be measured in eggs under different metabolic conditions, and will be compared with mathematical models of diffusion, reflecting expertise in mathematical and computational methods by the supervisory team. Measured time trajectories will reveal combinations of random, directed, transiently stalled and constrained motions related to crowded environments. The aim will be to develop a causal link between the nanostructure of the environment and particle motion. This in turn will stimulate hypothesis to be verified experimentally, and will provide an unprecedented insight on the cell’s interior.

Research Environment:
The student will be exposed to a vibrant multi-disciplinary environment at the physics/life science interface. They will join a well-funded academic team, with a successful history of supervising many students over the past 15 years, and an outstanding publication track record.
The project will start with two rotation mini-projects in the different co-supervisor labs. The student will be trained on a unique combination of skills, from operating optical microscopy instrumentation beyond state-of-the-art, to mathematical modelling and biological sample preparation techniques. Such a unique skillset will significantly boost future employability both in academia and in industry.

Training and Development Opportunities:
The supervisory team has strong links with companies, including microscope manufactures and image analysis software developers. Within this studentship, opportunities for visits/internships at these companies will arise. Global mobility opportunities will include visiting collaborating partner groups overseas, and participation to national/international conferences. The project will generate new knowledge and data that will be published in high quality journals.

Funding Notes

This is a fully-funded studentship which includes fees, stipend and a research and training support grant, for 3.5 years at UKRI rate, for home/EU students.

Self-funded international students are also welcomed to apply.

References

[1] doi: 10.1088/0034-4885/78/12/124601
[2] doi: 10.1016/j.tcb.2009.04.004
[3] doi: 10.1039/c9nr08512b
[4] doi: 10.1242/jcs.228999
[5] doi: 10.1002/stem.1088

How good is research at Cardiff University in Biological Sciences?

FTE Category A staff submitted: 54.70

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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