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Improving inner ear drug delivery by acoustic stimulation.


   UCL School of Life and Medical Sciences

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  Dr T Marquardt  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Applications are invited for a fully funded full-time PhD studentship at the UCL Ear Institute, co-supervised by Dr Torsten Marquardt and Dr Tobias Reichenbach (Imperial College London).

Background

An estimated 466 million people worldwide have disabling hearing loss. It affects approximately one in three people over the age 65 (WHO). While numerous cell-based therapies for the inner ear are currently under development, their application to the inner ear remains challenging as most of these therapeutic compounds need to be directly applied to the inner ear via the ear drum. However, the cochlea is a spiralled 35-mm long fluid-filled duct that can only be accessed at one end. Simple passive diffusion leaves a too-large concentration gradient so that the therapeutic compounds are currently not reaching their target tissue deep inside the cochlea. This project aims to develop methods of active drug transport along the cochlea by acoustic stimulation.

Two types of acoustic phenomena have shown potential:

1) A pumping action by large 4-Hz pressure oscillations in the ear canal. The hydrodynamic mechanism behind these experimental finding is not yet fully understood (https://doi.org/10.1016/j.isci.2020.100945).

2) Acoustic steady streaming. Its principal suitability for intracochlear drug transport has been shown in simplified two-dimensional computational models, but verification in more realistic models as well as experimental verification is still lacking (https://doi.org/10.1038/s41598-020-79946-z).

This project will extent the previous investigations to three-dimensional cochlear models of increasingly realistic geometry, utilizing the finite-element software package COMSOL. Finite-element models are an ideal tool to understand the fluid dynamics inside the cochlea, which is notoriously hard to access experimentally. By gaining a thorough understanding of the two mechanisms, the project aims to maximise the transport speed and achieve the most even distribution of the therapeutic compounds in the inner ear. The simulations will be validated by electro-physiological measurements.

The UCL Ear Institute includes a wide range of auditory scientists housed in a single institution. This multidisciplinary environment provides a unique opportunity to undertake research and receive world-class training in a range of state-of-the-art techniques used in hearing research. Interaction with different specialities will providing a great scope for career development.

Key requirements:

The successful PhD candidate will be involved in planning/programming of finite-element simulation. She or he will also generate Matlab software to organise, visualise, analyse and document the large amount of generated data in systematic way. The student will be trained further in running and analysing the electro-physiological experiments that will verify the simulations.

Candidates must have a good degree (2.1 or above) in acoustics, mechanical engineering, or physics. This position requires a solid knowledge in either acoustics or fluid-mechanics and a strong interest in combining numerical skills and experimental skills. Previous experience in finite-element modelling is of advantage and an existing interest in the biomechanics of the cochlea is desirable.

How to apply:

Formal applications should be submitted by email in the form of a CV, covering letter outlining motivation, interest, and suitability for this project, and contact details for two referees to Dr Torsten Marquardt ([Email Address Removed]), to whom informal inquiries should also be directed. Shortlisted candidates will be contacted directly for interview. The successful candidate is expected to start 20th September 2021.

Application deadline: 28 June 2021

Proposed interview date: 5-9 July 2021


Funding Notes

This studentship is funded for 3 years by the Royal National Institute for Deaf People (RNID) and includes UK home UCL PhD tuition fees, laboratory costs and an annual salary stipend starting at £17,000, increasing by £500 per year.

References

Lukashkin, A. N., Sadreev, I. I., Zakharova, N., Russell, I. J., and Yarin, Y. M. (2020). Local Drug Delivery to the Entire Cochlea without Breaching Its Boundaries. iScience, 23(3).
Sumner, L., Mestel, J. & Reichenbach, T. (2021). Steady streaming as a method for drug delivery to the inner ear. Sci Rep 11, 57.
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