Posted on: Monday, February 13, 2017
by Heloise Heau
Mike Bowl is a Senior Investigator Scientist at the Medical Research Council’s Harwell Institute in Oxfordshire. We are funding his research into genes involved in hearing loss.
In the UK, the government funds medical research via two main arms – the Department of Health and the Medical Research Council (MRC). I work at the MRC Harwell Institute, which is an internationally renowned centre for mouse genetic research.
Despite looking very different to mice, we share many of our genes with them (around 98%) and many of their body systems are very similar to ours. Studying genes in mice can help increase our understanding of genes in humans. At Harwell we use the mouse as a model organism to study and increase our understanding of the genes and pathologies associated with a range of human diseases and conditions, including diabetes, neurodegeneration, – and hearing loss.
The mouse has proved essential for the identification of many genes that, when incorrect, are associated with deafness. This has helped reveal more details about the complex mechanisms of hearing.
Our group at Harwell encompasses research into three different types of hearing loss – otitis media (glue ear), otopathogen studies, and sensorineural (hearing loss caused by damage to the inner ear). I’m the group leader for the sensorineural research team. We study the molecular processes underlying hearing, focusing on the specialised sensory and neural cells within the cochlea. These are the cells that detect sound vibrations and convert them into signals that are sent to the brain.
We’re born with a set number of cochlear sensory cells that are essential for hearing, but these cells can’t regenerate if they’re damaged (by excessive noise, or some cancer therapies, for example). I hope that my research will lead to a better understanding of how these sensory cells function, and how they can be protected from any damage.
The Harwell Ageing Screen is a large-scale project we carried out to identify genes associated with diseases, including hearing loss. Previously, these types of screens have been successfully used to identify dozens of disease-associated genes. But the Harwell Ageing screen is different in that mice are closely studied as they age (up to 18 months, which is relatively old for a mouse). Our aim was to identify genes that, when ‘perturbed’ or sent off course in any way, lead to age-related, progressive conditions.
The screen involved closely studying mice at particular time-points throughout their lives. We identified those with inherited hearing loss and used genome mapping to pinpoint the location of the responsible gene within their genome. DNA sequencing then enables us to read the code in the gene. Together, these techniques mean we can precisely determine the gene alteration causing the hearing loss – right down to the level of whether a single base in the DNA code has been incorrectly deleted or swapped for another one.
Our understanding of age-related hearing loss is currently very limited – as is our ability to come up with the best treatments. The Harwell Ageing Screen has allowed us to identify six novel genes critical for hearing in aged mice. This is exciting, as it will help pave the way forward in increasing our understanding of what underlies the condition in humans. In turn, this will increase our chances of coming up with a successful treatment.
Hearing loss in older age can be very isolating. As a nation we are, on average, living longer, so it seems appropriate that government and industry should focus their efforts towards finding therapies for chronic conditions such as progressive hearing loss.
Other than elderly relatives with hearing aids, I don’t have a personal connection to deafness, tinnitus, or hearing loss. My career choices have always been interest-led – I’d describe myself as a molecular geneticist who studies hearing and hearing loss.
Ever since childhood I’ve had a fascination with biology and how the human body works. At school, I found the science subjects the most interesting and rewarding. I followed this passion by studying for a degree in Medical Biochemistry at the University of Birmingham, and my doctorate at the University of Oxford. I feel very fortunate that I have a job doing something I really enjoy – the fact that my research will hopefully help people is an added bonus.
I’ve been fortunate to have two great mentors. The first, Professor Raj Thakker, supervised my DPhil studies at Oxford and gave me the encouragement and skills to follow a career in disease genetics. The second, Professor Steve Brown, here at the MRC Harwell Institute, gave me the opportunity to lead the sensorineural hearing loss research team.
Funding from Action on Hearing Loss has been pivotal to the work of my team. It’s helped to consolidate collaborations with other research teams (both within the UK and abroad) by providing ‘proof-of-principle’ funding to explore new avenues of research into age-related hearing loss. It’s also directly funded the salary of an up-and-coming auditory research scientist who’s been studying the role of a novel hearing loss associated gene.
Perhaps I’m biased but, in my opinion, the biggest recent ‘game changer’ has been the advances made in genome research techniques, such as whole genome sequencing and genome editing applications. These have revolutionised our ability to provide genetic diagnoses for patients with hereditary conditions such as hearing loss, and also allow researchers to more rapidly investigate the pathological changes associated with a particular gene defect.
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