Professor Walter Marcotti

Walter

Professor of Sensory Neuroscience
Wellcome Trust Senior Investigator
Department of Biomedical Science
The University of Sheffield
Firth Court, Western Bank
Sheffield S10 2TN
United Kingdom

Room: B1 221 Alfred Denny building
Telephone: +44 (0) 114 222 1098
Email: w.marcotti@sheffield.ac.uk

Centre for Sensory Neuroscience

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General

Brief career history

  • 2012 - present: Professor of Sensory Neuroscience
  • 2006 - present: Royal Society University Research Fellow, University of Sheffield, UK.
  • 2004 - 2005: Royal Society University Research Fellow, University of Sussex, UK.
  • 2001 - 2004: Postdoctoral Fellow, University of Sussex, UK.
  • 1997 - 2000: Postdoctoral Fellow, University of Bristol, UK.
  • 1994 - 1997: PhD, University of Pavia, Italy.
  • 1989 - 1992: University Degree in Biological Science, University of Pavia, Pavia, Italy.

Research interests

  • Molecular and physiological mechanisms controlling the functional maturation of the auditory system.
  • Mechanoelectrical transduction at the hair cell stereocilia
  • Signal processing at ribbon synapses
  • Age-related hearing loss
  • Mechanisms underlying different forms of hearing loss and deafness

Professional activities

  • Reviewing editor for Journal of Physiology
  • BBSRC Core panel member – Panel A
  • Grant reviewer for UK/EU Research Councils and Charities
  • Reviewer for many leading scientific journals

Awards and prizes

  • Wellcome Trust Senior Investigator (2014)
  • Sharpey-Schafer Lecture and Prize (2011) – Physiological Society, Oxford.
  • Royal Society University Research Fellowship (2004), The Royal Society, UK.

Full publications

Research

Auditory neuroscience and Deafness Sensory transduction Synaptic transmission

Sensory organs and the neural networks responsible for processing sensory information are supremely well adapted for detecting input from the external environment. Their challenge is to maximize sensitivity and fidelity over a wide dynamic range. The sensory receptors of the mammalian auditory system, the inner hair cells (IHCs), do this with unparalleled temporal precision (kHz range). We know little about the molecular and physiological mechanisms controlling the functional maturation of the auditory system or signal processing at the primary auditory synapses, the IHC ribbon synapses. Crucial to this work, is the need of near-physiological in vitro and the development of in vivo experimental models.

My laboratory is uniquely suited for this task because it is the only one in the world that routinely uses near-physiological conditions for in vitro mammalian cochlear physiology and performs in-vivo electrophysiology from the zebrafish.  How biological systems orchestrate their development and how complex signals are processed by mature neuronal networks are major challenges in the quest to understand human biology and disease.

The auditory system provides an ideal model with which to address these questions, primarily because it involves a highly ordered array of a very small number of sensory cells with well-defined neuronal circuitry. It is also a key priority for human health because hearing loss affects more than 360 million people worldwide (WHO 2013), a number that will increase with the aging population.

Figure 1

Funding

Collaborators

Teaching

Undergraduate and postgraduate taught modules

Level 3:

  • BMS355 Sensory Neuroscience
  • BMS349 Extended Library Project
  • BMS369 Laboratory Research Project

Masters (MSc):

  • BMS6355 Sensory Neuroscience
Opportunities

PhD Project

Title: Understanding the functional role of adhesion molecules in the synaptogenesis of ribbon synapses in mammalian auditory system

Supervisor 1: Professor Walter Marcotti

Supervisor 2: Dr Steve Brown (MRC Harwell)

Funding status: Competition funded project European/UK students only

This project is eligible for a department scholarship. These scholarships are awarded on a competitive basis – find out more on our funding webpage.

Project Description

Hearing is profoundly important in order to perceive information from the outside world and its loss can have a dramatic impact on our daily lives. The perception of hearing depends on the transduction of sound waves into an electrical signal in the auditory organ, the cochlea, which is then transmitted to the brain via auditory afferent neurons. Crucial to this physiological process is the precise, rapid and continuous release of the neurotransmitter glutamate from highly specialized ribbon synapses at the basolateral membrane of sensory inner hair cells (IHCs) located in the mammalian cochlea, which are juxtaposed to the afferent auditory terminals.

We have recently shown that a mutation that affects Neuroplastin caused a failure in the normal synaptogenesis of ribbon synapses in IHCs (Carrott et al 2016). Neuroplastin is a member of the Basigin group of neuronal and synapse-enriched glycoproteins belonging to the immunoglobulin (Ig) superfamily of neural cell adhesion molecules (CAMs), which also includes Basigin and Embigin. All these CAMs are expressed in the mammalian cochlea. Currently, we lack any understanding on the role of Basigin and Embigin on hearing function, as well as the specific involvement of the two encoded Neuroplastin protein isoforms - Neuroplastin-65 and Neuroplastin-55. We will use a combination of well-established and state-of-the-art techniques, together with transgenic mouse models lacking these CAMs to address the hypothesis that this group of proteins is crucial not only for the acquisition, but also for the maintenance of IHC ribbon synapses in hair cells, and as such playing a primary role in hearing. We will also test the hypothesis that these genes are involved age-related hearing loss.

The project will involves a collaboration between the laboratories of Prof Walter Marcotti (Wellcome Trust Senior Investigator, University of Sheffield) and Prof. Steve Brown and Dr Mike Bowl (Director and Project leader, respectively, at the MRC Harwell Institute) who are world-wide experts in hearing and also in the different aspects of this project. You will be trained in a wide-range of in vitro and in vivo techniques, such as patch clamping and 2-photon confocal microscopy, together with the latest techniques in gene expression and mouse genetics. You will also benefit greatly from the wide range of expertise present in the two Institutions through joint lab meeting that are held on a regular basis.

You will complete your PhD having gained a wide range of highly desirable skills, providing a firm foundation for a career in academia or industry. 

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

References:

Carrott, L., et al., (2016) Absence of neuroplastin-65 affects synaptogenesis in mouse inner hair cells and causes profound hearing koss. J Neurosci, 36: 222-34.

Contact information

For informal enquiries about the project or application process, please feel free to contact:

For further information about these projects and how to apply, see our PhD Opportunities page:PhD Opportunities

Selected publications

Journal articles