PhD in homogenous distribution of therapeutic agents along the cochlea by acoustic stimulation at UCL/Imperial College

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 age 65 (WHO). While numerous developments of therapeutic compounds for the inner ear are currently under way, their application to inner ear remains challenging as many of them cannot be administered systemically through the blood-labyrinth barrier. Thus, application via the middle ear is often the only route. However, the cochlear is a spiralled 35-mm long fluid-filled duct, which is embedded in bone. Because this duct is only accessible at one end, a pronounced concentration gradient remains, after injecting or diffusing the therapeutic compounds through the accessible round window.

Two types of acoustic phenomena have shown potential to facilitate the even distribution of compounds along the cochlear spiral:

1) A large-amplitude 4-Hz pumping action by large pressure 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 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 state-of-the-art techniques. Interacting with different specialities is encouraged, providing greater scope for career development.

Key requirements:

The successful PhD candidate will be involved in planning/programming of finite-element simulation. She or he will generate software to organise, visualise, analyse and document the large amount of generated data in systematic way. The project will furthermore require to design, implement, run and analyse the physiological experiments that will verify the simulations.

Candidates must have a good degree (2.1 or above; or equivalent EU/overseas degree) 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 sensory neuroscience and 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 (t.marquardt@ucl.ac.uk), 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: 19 May 2021

Proposed interview date: 24-28 May 2021