Dr Stuart Johnson

Stuart Johnson

Royal Society University Research Fellow
Department of Biomedical Science
University of Sheffield
Western Bank
Sheffield S10 2TN
United Kingdom

Room: B1 220 Alfred Denny building
Telephone: +44 (0)114 222 3692
Email: s.johnson@sheffield.ac.uk

Centre for Sensory Neuroscience

CMIAD Logo

General

Brief career history

  • 2011-present: Royal Society University Research Fellow, University of Sheffield, UK.
  • 2009-2011: RNID Postdoctoral Fellow, University of Sheffield, UK.
  • 2006-2009: Wellcome Trust Postdoctoral Fellow, University of Sheffield, UK.
  • 2003-2005: MRC Postdoctoral Fellow, University of Sussex, UK.
  • 1998-2003: D.Phil, University of Sussex, UK.
  • 1995-1998: BSc Hons Biological Sciences (Animal Physiology), University of Leicester, UK.

Research interests

Signalling characteristics of cochlear hair cells

Professional activities

Invited Seminars

  • Sandbjerg Meeting on Membrane Transport, Denmark (2015)

Awards

  • Royal Society University Research Fellowship (2011)

Full publications list

Research

Auditory neuroscience, Sensory coding, Synaptic transmission

Mammalian cochlear inner hair cells (IHCs) are the primary sensory cells of the auditory pathway. Their job is to convert sound vibrations into an electrical signal that can be interpreted by the brain. As such, it is vital that the information encoded by IHCs is accurately preserved at this initial stage. One of the major causes of deafness/hearing loss is associated with IHCs losing their ability to function normally.

The aim of my research is to find out how IHCs are able to accurately encode sounds over a wide frequency and intensity range and how the information is processed on its way to the brain. Knowledge of how the ear processes sound will be informative to develop improved hearing aids, including cochlear implants. An additional aspect of my research applies directly to define how stem cells are able to replace damaged nerve fibres in order to restore hearing (in collaboration with Prof Marcelo Rivolta).

In order to achieve this I will study IHCs in the isolated cochlea using a combination of electrophysiological, cell imaging and molecular biological techniques.

Figure 1

Collaborations

  • Henrique von Gersdorff (Vollum Institute, USA)
  • Robert Fettiplace FRS (Wisconsin, USA)
  • Marcelo Rivolta (Sheffield)

Funding

  • The Royal Society
  • Action on Hearing Loss
Teaching

Undergraduate and postgraduate taught modules

Level 3:

  • BMS349 Extended Library Project
Opportunities

PhD Studentship starting October 2017

Title: Exploring re-innervation and synaptogenesis between human stem cell-derived auditory neurons and inner hair cells: A therapeutic model for ‘hidden hearing loss’

Supervisors: Professor Marcelo Rivolta and Dr Stuart Johnson

Finding: Competition funded project European/UK students only.

Project Description

Loud noise exposure and aging lead to the permanent loss of afferent synaptic contacts to the primary sensory inner hair cells (IHCs) in the cochlea, whilst causing only a temporary or undetectable hearing threshold shift. This ‘synaptopathy’ reduces IHC afferent innervation by up to 50% leaving an individual unable to detect sounds in a noisy environment and experiencing difficulties with speech discrimination and intelligibility. Since the hearing thresholds are unaltered, it is difficult to detect the condition using conventional hearing tests, hence it is named ‘hidden hearing loss’. The loss of synaptic contacts is also thought to underlie primary neural degeneration in acquired hearing loss and aging.

The causative mechanisms underlying cochlear synaptopathy are not well understood. While it is believed to be a result of the toxic effects of overstimulating these fibres, it is not known whether there are any changes in the properties of the IHCs that lead to axonal retraction or, conversely, whether there are any IHC changes that result from it.

Experimental Plan
We have developed a way to make organotypic cultures of the excised mature mammalian cochlea and record from the sensory IHCs for 11 days in-culture. Interestingly, we found that after one or two days in culture the IHCs lose the physiological characteristics of mature cells and revert to a more immature phenotype without showing signs of degeneration or death. The PhD student will learn to make these cultures and use them to define the progression of this cell ‘de-differentiation’ using electrophysiological recording, staining and immunolabelling to see whether it is triggered by neuronal retraction or vice versa.

We have previously shown that human embryonic stem cell-derived spiral ganglion neurons (SGNs) can be transplanted into an animal model and establish synaptic connections and recovery of function. To address the specific role of the afferent fibres the student will learn to co-culture the adult gerbil organ of Corti with hESC-derived SGNs to see if the IHC properties have changed in order to attract new fibres and/or whether new synaptic innervation of the hair cells can restore their mature phenotype.

This study will allow us to understand the chain of events that lead to the ‘de-differentiation’ of IHCs in culture and whether it can be reversed by re-innervation from stem cell-derived SGNs. The advantages of using the mature organotypic culture as a model system to study IHC and afferent fibre synaptopathy, and cochlear plasticity in general, are that the conditions can be easily manipulated whilst monitoring the characteristics of the IHCs and afferent fibres throughout.

Impact
An understanding of cochlear plasticity in response to aging or trauma, and how to prevent or control it, will be essential for alleviating the effects of cochlear synaptopathy. This knowledge will also be important for slowing the progression of age-related hearing loss as well as the treatment of other poorly understood perceptual phenomena like tinnitus, the sensation of phantom tones, and hyperacusis, a reduced tolerance to moderate level sounds, all of which affect billions of people worldwide.

Keywords: Biophysics, Cell Biology / Development, Molecular Biology, Neuroscience / Neurology, Biophysics

References

  • Kujawa SG, Liberman MC (2015) Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss. Hear Res 330: 191-199.
  • Johnson SL (2015) Membrane properties specialize mammalian inner hair cells for frequency or intensity encoding. eLife 4 pii: e08177
  • Chen W, Jongkamonwiwat N, Abbas L, Jacob Eshtan S, Johnson SL, Kuhn S, Milo M, Thurlow JK, Andrews PW, Marcotti W, Moore HD, Rivolta MN (2012) Restoration of auditory evoked responses by human ES-cell-derived otic progenitors. Nature 490: 278-282.

Further information about this project can be found on our PhD Opportunities page:

PhD Opportunities

Selected publications

Journal articles