IvyTies Academic Job

Homogenous distribution of therapeutic agents along the cochlea by acoustic stimulation

University College London

United Kingdom

Application deadline : 2021-05-19

Email :  t.marquardt@ucl.ac.uk

Summary

Type of job opening :PhD

Subject Area(s) :Acoustics Biophysics General (Engineering) Medical / Biomedical Physics Neuroscience / Neurology Physiology & Sports Science

Job Description

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, and it affect approximately one in three people over age 65 (WHO). While many 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 due to the blood-labyrinth barrier. Thus, application via the middle ear is often the only option. However, the cochlear is a spiralled 35-mm long fluid-filled duct, which is embedded in bone. Since this duct is only accessible at one end, a pronounced concentration gradient along this duct remains, after injecting, or diffusing the therapeutic compounds through the round window.

Two types of acoustic phenomena have shown potential to facilitate the efficient distribution of compounds along the cochlear spiral: 1) A large-amplitude 4-Hz pumping action of the stapes. (https://doi.org/10.1016/j.isci.2020.100945

; The hydrodynamic mechanism behind these experimental finding is not yet fully understood). 2) Acoustic steady streaming. (Its principal suitability for intracochlear drug transport has been shown in simplified two-dimensional computational models (https://doi.org/10.1038/s41598-020-79946-z), but verification in more realistic models as well as experimental verification is still lacking.)

This project will extent 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 both 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 then validated by physiological measurements.

This research will lead to novel ways to effectively deliver therapeutic compounds to their target location in the inner ear. This is currently still a big challenge in the development of inner ear therapies, including those that may benefit patients with tinnitus.

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 specialties is encouraged providing greater scope for career development.

Desired Qualifications

The successful PhD candidate will be involved in planning/programming of finite-element simulation and organize, analyzing, and document a large amount of generating data in a systematic way. The project will furthermore require to design, implement, run and analyze the experiments to verify the simulations.

Candidates must have a good degree (2.1 or above; or equivalent EU/overseas degree) in acoustics, mechanical engineering, or physics with specialization in acoustics or fluid mechanics. This position requires a piece of solid knowledge in either acoustics or fluid-mechanics and a strong interest in combining numerical skills and experimental skills. Previous experience in finite-element modeling is of advantage and an 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, a covering letter outlining motivation, interest, and suitability for this project, and contact details for two referees to Kristina Dr, Torsten Marquardt (t.marquardt@ucl.ac.uk), to whom informal inquiries should also be directed. Shortlisted candidates will be contacted directly for an interview. The successful candidate is expected to start on 20th September 2021.

Application deadline: 19 May 2021

Proposed interview date: 24-28 May 2021