Investigating gap junction formation in the cochlea
The 2nd Deafness Research UK UCLEI Postgraduate Studentship was awarded to John Kelly, who is working with Dr Daniel Jagger at the UCL Ear Institute in London.
[Studentship: 2006-2010]
In addition to sensory “hair cells”, the inner ear contains support cells that help maintain the right chemical environment for the hair cells to survive and work correctly. Support cells are connected to each other by small, tube-like channels called gap junctions, forming a network through which small molecules can pass.
Connexins are proteins that form component parts of the gap junctions, which allow support cells to pass chemical signals through the network. There are two types of connexin in the inner ear of mammals: Cx26 and Cx30. Mutations in either of these connexins cause deafness, however, their role and function are not fully understood.
The aim of John’s initial research is to study the route Cx30 takes to travel from the part of the cell in which it is made to the cell membrane. This is important because there have been conflicting reports on different pathways taken by the other connexin, Cx26, on its way to the cell surface, but it is known that the two proteins must bind together to form a gap junction.
The research team are interested in how and where these two proteins bind together and why a single mutation in either connexin causes deafness.
At present it is not known where inside the cell Cx26 and Cx30 first bind together to form functional proteins. Knowing where this happens will allow the team to compare normal cells to those cells with a connexin mutation to observe the effects. It could be that a mutation prevents the connexin from reaching the cell surface to form gap junctions, or it might prevent Cx26 and Cx30 from binding together.
John will also try to look directly at the effects of connexin mutations on the structure and physiology of the inner ear.
Results from the study will shed light on how connexin mutations can lead to faulty gap junctions and could eventually lead to possible therapeutic techniques to try and prevent hearing loss.
