Research

Faculty of Medicine, Dentistry & Health Sciences: Dept of Otolaryngology

Department of Otolaryngology Open Day
Tuesday 9 September 2008 2pm to 4pm
Lucy Jones Hall, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne

 

Research Overview

 

The Department of Otolaryngology’s research activities are focused on studying the neurobiology of deafness, improving speech perception for cochlear implant users, and understanding language development in children who are hearing impaired.

The research programs are principally supported by international and national peer-reviewed funding awarded to the Department’s senior researchers. Major Departmental funding support is provided by the National Health and Medical Research Council (NHMRC), the Australian Research Council and the Garnett Passe & Rodney Williams Memorial Foundation.

The Department is also a core party of the CRC for Cochlear Implant and Hearing Aid Innovation (CRC HEAR).

The Department also undertakes collaborative research with The Bionic Ear Institute.

Key research activities undertaken by Departmental researchers include the following:

Current Research Projects Available

2008/2009

Differentiation of stem cells into functional auditory neurons
Supervisor: Dr Bryony Coleman
Project suitability: Advanced Medical Science, Honours, Undergraduate Research Opportunity Program

Investigating both the differentiation and functional activity of stem cells is an integral component to developing successful cell replacement therapies for disease. To date this area is still poorly understood, particularly in the field of auditory neuroscience. Several in vitro models have been used to successfully differentiate of mouse embryonic stem cells into bipolar neurons and the fate and differentiation of these stem cells following their transplantation into the deaf cochlea has been examined.

This project will continue to investigate the potential to differentiate mouse and/or human embryonic stem cells toward an auditory neural lineage in vitro. Successful applicants will be trained in primary cell and tissue culture, co-culture, stem cell maintenance and differentiation, immunohistochemistry, basic microscopy and fluorescence confocal imaging. For PhD applicants, the project may include functional analyses of differentiated cells in vitro, and potentially in vivo.

The long-term aim of Dr Coleman's research is to produce a population of sensory neurons from embryonic stem cells that can be used with a cochlear implant to improve speech perception. She collaborates with scientists at Harvard Medical School and Johns Hopkins University on several aspects of this project.


Improving speech perception by users of cochlear implants
Supervisor: Professor Richard Dowell
Project Suitability: Advanced Medical Science, Masters of Audiology Research Project.


Chronic Recording in the Freely Behaving Animal
Supervisor: Dr James Fallon
Project suitability:  Advanced Medical Science, Honours, Masters,  Doctor of Medicine, Ph.D,  Bachelor of Medical Science, Masters of Audiology Research Project.

The organisation of the auditory pathway in neonatal animals, which has been laid down by genetic cues, is rudimentary at best. It is only with exposure to behaviourally meaningful auditory input and experience, that the central auditory pathway can be driven to become highly organised. Additionally, it is thought that this organisation occurs irrespective of whether the auditory input is from normal acoustic hearing, or chronic intra-cochlear electrical stimulation (i.e. the use of a cochlea implant). This project will study of the plastic response, over time, the deafened auditory pathway to chronic intra-cochlear electrical stimulation by: developing hardware and protocols to be used for the chronic recording of single and multi-unit data in the freely behaving animal; and using these techniques to investigate changes in cochleotopic organisation of, and temporal processing within, the central auditory pathway.

 

Characterisation of the response of the auditory cortex to intra-cochlear electrical stimulation
Supervisor: Dr James Fallon

Project Suitability:  Advanced Medical Science, Honours, Masters,  Doctor of Medicine, Ph.D,  Bachelor of Medical Science, Masters of Audiology Research Project.

Intra-cochlear electrical stimulation, similar to that received by patients with a cochlear implant, results in activation of the auditory cortex. This project aims to characterise this activation, by recording from neurons within the auditory cortex of the rat, as a first step in examining the effects of chronic stimulation on brain plasticity. An individual with an interest in working with animals and a background in biological sciences would be best suited for this project.

 

Multichannel neural recording and microstimulation of auditory brainstem: implications for auditory brainstem implant
Supervisor: Associate Professor Tony Paolini
Project suitability: Advanced Medical Science, Honours, Masters; Doctor of Medicine; Ph.D, Bachelor of Medical Science; Masters of Audiology Research Project.

Understanding the complexities underlying brain processing is a crucial step in the development of devices that can artificially drive neural systems. The auditory system has provided an avenue where this can be investigated with the development of the Auditory Brainstem Implant (ABI). The ABI is designed to provide sound information to individuals who have peripheral hearing nerve damage which prevents the use of cochlear implants. It has been used predominantly in patients with bilateral Neurofibromatosis Type 2 auditory nerve tumours, cochlear ossification, cochlear nerve aplasia and posttraumatic avulsion. The ABI in the most part has had limited success, mainly providing awareness of environmental sounds. By further extending our knowledge of auditory processing, we aim to better resolve stimulation strategies and implant design for successful implantation and restoration of hearing.


Gene transfer technology for maintaining and regenerating auditory nerves after hearing loss
Supervisor: Dr Rachael Richardson
Project Suitability: Advanced Medical Science, Honours, PhD

Many types of deafness result in progressive degeneration of auditory neurons. Experimental research has proven that providing neurotrophins to the cochlea can maintain auditory neuron survival for short periods of time. We are now interested in methods of promoting longer-term nerve survival and more controlled regeneration using gene transfer technology. This project will use in vitro tissue culture (see picture) and in vivo surgical techniques to investigate gene transfer in the cochlea. The genes for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) have been placed in adeno-associated virus and adenoviral vectors. Viral particles containing the BDNF or NT3 genes will then be added to the cultures or to the cochleae of guinea pigs in order to investigate the effect of neurotrophin gene expression on nerve survival and regeneration after sensorineural hearing loss.

Techniques that you will learn:

* Animal handling skills
* Micro-dissection
* Micro-surgery
* Sterile technique
* Primary tissue culture
* Molecular biology techniques eg DNA amplification.
* Immunofluorescent staining
* Fluorescent and light microscopy
* Imaging and analysis
* Statistical analysis of results

 

The effect of early auditory deprivation on musical enjoyment and the development of musical skills in children with cochlear implants
Supervisor: Dr Julia Sarant
Project suitability: Advanced Medical Science, Honours, Master of Audiology Research Project

The majority of studies investigating the music perception of cochlear implant (CI) users have assessed adults who have lost their hearing later in life. As a result their auditory systems have usually developed hearing a normal representation of music. To accurately perceive music post implantation, the adult brain must adapt to the disparity between music heard through a normally hearing system and the distorted musical signal heard via a CI. It is unclear to what extent such adaptation is possible within the adult brain. Child CI users on the other hand have the advantage of inherently more plasticity in the developing brain. Furthermore, the lack of experience child CI users have with music prior to implantation means that they do not have preconceived ideas as to how music should sound. The combination of these factors may potentially lead to child CI users attaining greater music perception and enjoyment than that achieved by their adult counterparts. The aims of this study are to: 1. investigate the effect of early auditory deprivation on the development of musical skills and enjoyment and, 2. determine if a relationship exists between age at implantation, and music perception and enjoyment. The student undertaking this study would be required to collect music perception and appraisal data from around 50 adolescent CI users.

 

The effect of stimulation rate on T- and C- Levels
Supervisor: Dr Julia Sarant
Project suitability: Advanced Medical Science, Honours, Master of Audiology Research Project

When programming a cochlear implant it is necessary to determine the minimum level of stimulation required to evoke an auditory response (i.e. a T-Level) and the highest level of stimulation deemed comfortable by the user (i.e. a C-Level) for each electrode. For a number of years average T- and C-levels across patients have been relatively stable and dependent upon the rate at which the electrodes are stimulated. However, with recent advances in cochlear implant hardware and surgical implantation techniques, there have been anecdotal reports of a reduction in the average T- and C-Levels recorded by clinicians. Furthermore, the relationship between T and C-Levels and rate of stimulation appears to have weakened. It is postulated that the electrode contacts of the currently implanted electrode arrays are in closer proximity to the auditory neurons they stimulate, potentially stimulating a smaller population of auditory neurons than they may have with earlier electrode arrays and surgical techniques. The aim of this study is to determine if the anecdotal reports of a reduction in T- and C-Levels, and weakening of the relationship between stimulation rate and T- and C-Levels are correct. Initially the student undertaking this study would be required to collect psychophysical T- and C-Levels at various stimulation rates for two groups of adult cochlear implant users. One group with < 1 year experience with the implant and one group with > 5 years experience with the implant. A total of 24 subjects would be assessed. A number of speech processing programs (MAPs) using the different rates of stimulation would be created, using the psychophysical data, and compared for sound quality and, potentially, speech perception outcomes.


The effects of trophic agents on the auditory nervous system
Supervisor: Dr David Sly
Project suitability:  Advanced Medical Science, Honours, Masters, Ph.D, Master of Audiology Research Project, Undergraduate Research Opportunity Program

Cochlear implants restore hearing by direct electrical stimulation of the auditory (hearing) nerves. The success of the implant is therefore dependent upon the integrity and function of these nerves. In a healthy ear, the auditory nerve is normally maintained by the release of nerve growth factors from hair cells, but when these are lost in deafness, there is severe degradation of the auditory nerve with time. However, the application of nerve growth factors to the deafened cochlea arrests hearing nerve degeneration and is potentially of major importance to cochlear implantation.

This project examines how biological interventions with nerve growth factors can affect the structure of the auditory nerve and its response to cochlear implant stimulation. We are particularly interested in working out how longer periods of deafness and neurotrophin treatment and varying dosages of neurotrophins affect these outcomes in the hope that they may be understood prior to clinical application of nerve growth factors.

You will gain experience with:

* Cochlear implant surgery in small animals
* Single neuron electrophysiology
* Cochlea and auditory brain anatomy and histology
* Fluorescent and light microscopy
* Data analysis

 

Electrophonic Hearing with a Cochlear Implant
Supervisor: Dr David Grayden
Project suitability: Masters, Ph.D

Electrophonic hearing results from vibrations in the inner ear caused by electrical stimulation. These vibrations can eliciting hearing. Recently, some cochlear implant users have usable low-frequency hearing in the same ear as their implant. This project will investigate using the cochlear implant to generate electrophonic hearing in the low frequencies that will provide improved speech recognition, sound localisation and music perception to users.


Fine-grained Timing Information for Cochlear Implants
Supervisor: Dr David Grayden
Project suitability: Masters, Ph.D

Current cochlear implants use coarse frequency and timing information to convey sounds to users. Higher rates of stimulation are now possible with modern cochlear implants, so it is possible to provide more fin-grained timing cues by precisely controlling the time of stimulation. This project will investigate algorithms for controlling timing cues so provide stimulation that may help users to better perceive speech in noisy situations and better perceive music.



A healthy start to life: preventing congenital deafness due to protease mutations with timely thyroid hormone supplementation
Supervisor: Dr Justin Tan
Project Suitability: AMS

A mutation in a serine protease gene, the TMPRSS1 gene, causes congenital deafness in mice. We have identified the cellular and molecular pathology of this deafness. Low thyroid hormone levels in these mice appear to contribute to this deafness. We aim to supplement thyroid hormones to determine if we can restore hearing to these mutant mice. This project has a clinical relevance because mutations in a related serine protease gene, the TMPRSS3, cause deafness in humans.


Techniques: Minor animal surgery, hearing threshold measurements, some molecular biology (eg genotyping, immunohistochemistry)

 

Modelling the auditory nerve response to cochlear implant stimulation: improving speech processors
Supervisors: Leon Heffer, Dr David Sly, Professor Stephen O'Leary
Project Suitability: Advanced Medical Science, Honours, Master of Audiology Research Project, Undergraduate Research Opportunity Program

This project stems from our recent success at developing a mathematical model that can accurately predict the firing responses of single auditory neurons to complex electrical stimulation. This model has far-reaching implications for speeding the development and improvement for all types of neural prostheses, including the cochlear implant.

The project will investigate:

Testing and refinement of the model using different types of patterned electrical stimuli.
Expansion of the model to include a desired target response (the response to acoustical stimulation).
Testing the model in deafened animals to determine whether degenerating nerves perform similarly to healthy nerves.
Testing the model in human cochlear implant recipients.
The applicant will ideally have a keen interest in neuroscience, computer programming, mathematics and electronics.

The project will offer:

Small animal neurosurgical training
Laboratory and clinical setting experience
Cross disciplinary research (neuroscience, surgery, engineering, behavioural science)
Animal handling skills

 

Preventing hearing loss during surgery to the ear

Supervisor: Professor Stephen O'Leary
Project suitability: Advanced Medical Science, Honours, Doctor of Medicine, Ph.D, Master ofAudiology Research Project, Undergraduate Research Opportunity Program

This NHMRC funded project aims to reduce the risk of hearing loss during surgery or medical interventions, such as chemotherapy to treat cancer. Hearing loss during cochlear implantation is of particular interest, since the aim of implant surgery is now to combine both natural hearing and the cochlear implant. This is a translational research project that is defining clinically applicable ways of delivering protective drugs to the inner ear prior to medical and surgical interventions. We conduct basic research into the modes and timing of delivery of therapeutic drugs to the inner ear, and clinical trials. This project would suit those with an interest in surgery, clinical medicine, audiology, hearing sciences or biomedical engineering.

Virtual Reality Surgery
Supervisor: Professor Stephen O'Leary
Project Suitablility: Advanced Medical Science, Honours, Doctor of Medicine, Ph.D, Master of Audiology Research Project, Undergraduate Research Opportunity Program

Virtual reality (VR) surgery is the way in which surgeons of tomorrow will be taught. VR surgery involves immersion into a 3D world where the patient can be touched and operated on. The Department of Otolaryngology has developed a virtual reality surgical environment for ear surgery, which has been commercialised by the Australian company, Medic Vision, and was the recipient of the University's Knowledge Transfer Award for 2008. We are involved in exciting research that will determine how best to train surgeons in VR, and provide real-time feedback to trainees. This research will interest to students with an interest in surgery, or computer science. 

 

Repairing the auditory system with cochlear implantation and drug delivery
Supervisor: Dr Andrew Wise
Project Suitability: Advanced Medical Science, Honours, PhD

A common cause of deafness is the loss of sensory hair cells in the inner ear that normally convert sound into nerve impulses. The cochlear implant works by electrically exciting auditory nerves directly to bypass the sensory hair cells that are either damaged or absent. However, auditory nerves degenerate after deafness leading to a significant reduction in their population and changes in the response characteristics of the auditory pathway to electrical stimulation. The aim of this research project is to restore function to the deaf inner ear using a cochlear implant and/or with the delivery of drugs to protect and regenerate auditory nerves.

 

 

 
 
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