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Sally Dawson

Sally Dawson is a Lecturer in Molecular Audiology.

People often ask “Is a disease or condition caused by nature or nurture?” – in fact a lot of the most common diseases are caused by a combination of these two things. I have always been interested in how an individual’s genes and their environment combine to cause disease and this is one of the things I am studying in hearing loss. I did my PhD in cardiovascular genetics where I learnt about how to study the genetics of complex diseases. When I left I spent some time studying the role a group of genes in the nervous system and by chance one of them turned out to be important in hearing. That’s the kind of think that can happen in research –you suddenly get taken in a completely new direction.

It was actually quite timely because I was ready to move back into an area of research which was more clinically relevant and was also keen to set up my own group. Here at the UCL Ear Institute it is quite unusual in that there are lots of people working on the same disease but from different points of view which can be very challenging but the building we’re in (Centre for Auditory Research) facilitates interdisciplinary learning by forcing interactions between groups. This has already proven to be successful –I now have a collaboration with Jonathan Gale’s group and we run some joint research projects together. We’ve also got an interaction with clinicians at the hospital next door which is beneficial for us in terms of getting patient samples and also encouraging clinicians to become more involved in research.

Research.

People sometimes have the impression that in genetics we are just interested in finding which gene is involved in a disease and that is the end of the story. However what we are really interested in is the actual mechanisms of the disease – using genetics to find out what goes wrong in hearing loss, especially age related hearing loss which is very common. We don’t really know what the processes are that cause hair cells to die in the inner ear and that’s what we’re trying to work out, because if we can work out what’s going wrong then maybe we can intervene at some point and correct or prevent the damage.

There are 2 main aspects of our work:

1: identifying susceptibility of genes for age related hearing loss- looking at how genes differ in people who are prone to hearing loss and understanding the way this increases their risk. Widespread hearing loss is known to be caused by both genetic and environmental factors eventually leading to loss of hair cells in the inner ear. However, it remains unclear why some individuals lose their hearing as they get older while others in the same environment remain undamaged. One explanation is that genetic variation means some individuals are more susceptible to hearing loss caused by environmental damage. We are taking a candidate gene approach to look for common functional changes in genes which may pre-dispose some individuals to hearing loss.

2: survival mechanisms in hair cells (in collaboration with Jonathan Gale’s Group). One of the reasons that the causes of age related hearing loss remain unclear is that we know very little about the molecular pathways of the hair cell. It is loss of the hair cell which is the precipitating cause of hearing loss. The inner ear is frequently subjected to potentially damaging environmental insults such as excessive noise. How the sensory receptor hair cells respond to such stimuli determines whether an insult is pathogenic or is successfully repaired. Deciphering the molecular mechanisms involved in these responses is therefore a pre-requisite to developing interventions to halt or reverse the damage. We have used a subtractive hybridisation strategy to identify a pool of genes whose expression is altered by two hair cell survival factors, Brn-3c and Barhl-1. As part of a collaboration with Dr Jonathan Gale (also at CAR), testing is underway to characterise the role of genes selected from this pool in protecting hair cells from damage and to decipher molecular survival pathways. The aim of our research is to: 1) identify the mechanisms which protect and maintain hair cell function; 2) develop subtractive hybridisation strategy was then used to identify a pool of genes whose strategies to improve the survival of hair cells; 3) test the efficacy of these in protecting against damage.

We gratefully acknowledge the following organisations for funding our research:- Deafness Research UK, Royal National Institute for the Deaf, Johnson & Johnson, Help the Aged and the Wellcome Trust. We would also like to thank the many patients who have volunteered to take part in our research.