Xin-Yu Zhou is a PhD student in Dr Torsten Marquardt’s lab at University College London. The studentship began in 2021.
Background
Most hearing loss results from damage to specialised sound-sensing cells inside the inner ear, or cochlea. These cells, called hair cells, normally convert sound information in the air (which is mechanical) into electrical signals which are then sent to the brain. When damaged, these cells can currently not be repaired or replaced, and so the hearing loss caused as a result is permanent.
Researchers around the world are working to develop treatments that can repair hair cells or re-grow them. A persistent problem with such treatments is that it is still difficult to transport potential treatments to the hair cells inside the cochlea where they are needed. The cochlea is enclosed within the temporal bone of the skull, which is the hardest bone in the body, and is therefore hard to access. There is a small ‘window’ in this bone inside the middle ear, covered with only a thin membrane of connective tissue, which provides access to the cochlea for drugs or other treatments. It can be accessed surgically via the eardrum and the middle ear. However, the hair cells that are responsible for detecting the sounds that matter most for speech are located towards the end of the cochlea which is furthest from this ‘window’. It is therefore difficult for treatments to reach these cells when introduced into the cochlea through this window.
Aims
This research project will pioneer two new methods for transporting drugs to the target hair cells at the opposite end of the cochlea. These methods take advantage of the particular way in which the fluid inside the inner ear moves in response to sound or other factors. The aim is to better understand how each method works, and to measure (and if possible, improve) their effectiveness. The student will use both computational and experimental approaches to carry out this work.
The student will initially use computational modelling techniques to simulate the movement of fluid inside the inner ear. This will give them a better understanding of how the new methods may work to push drugs along the length of the cochlea. Computer models can be used to investigate phenomena at very small scales as well as in situations where it may not be easy to carry out experimental investigations. They are therefore an ideal way of understanding fluid movement inside the tiny cochlea that is notoriously difficult to access experimentally. Specialised software running on a powerful computer will be used to investigate and further develop the two new methods for direct drug delivery into the inner ear.
Following the modelling work, the student will then carry out drug-delivery experiments in guinea pigs to validate their computer modelling work. The student will inject a drug that blocks hearing into the cochlea, and monitor the speed at which the drug moves along it. They will do this by measuring how the brain’s response to test sounds is affected by the substance. In particular, they will be looking for a decreased or missing response to sound – this will mean that the drug has reached the part of the cochlea that responds to sounds at that particular frequency (or pitch).
A comparison between the experimental results and the simulated predictions will validate the accuracy of the computer model.
Benefit
This research could lead to new ways to effectively deliver drugs or other types of treatment 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.