Dr Tanya T Whitfield

Tanya Whitfield graduated in Natural Sciences (Zoology) from the University of Cambridge in 1989, and undertook PhD and postdoctoral studies there with Chris Wylie, working on development and patterning of the early Xenopus embryo. In 1994, she was an EMBO short-term fellow in the lab of Christiane Nüsslein-Volhard in Tübingen, Germany, where she began analysis of a series of zebrafish lines with defects of the developing ear. She continued as an Imperial Cancer Research Fund postdoctoral fellow in the lab of Julian Lewis, first at the ICRF Developmental Biology Unit in Oxford, and later in London. Dr Whitfield established her research lab at the University of Sheffield in 1997, and is a Senior Lecturer in the Department of Biomedical Science. The Whitfield lab studies the genetic control of patterning in the early otic vesicle, in particular focussing on otic patterning and models for human deafness.

Research

Summary for nonspecialist

The inner ear is the organ that mediates our senses of hearing and balance. It consists of an intricate fluid-filled labyrinth housing a variety of extraordinarily sensitive sensory structures that respond to sound, movement and gravity.

For correct inner ear function it is essential that each of these components form in exactly the right place in the embryo, as any abnormalities can lead to deafness or balance disorders.Indeed, congenital deafness is an important clinical problem, affecting approximately one in every thousand children at birth.

Our aim is to understand how the inner ear develops in the embryo, and the mechanisms that ensure that the different cell types in the ear arise in the correct positions so that they can function accurately.

We use embryos of a small tropical fish, the zebrafish, in our research, as this fish is a superb model for the study of vertebrate inner ear development.

Three dimensional reconstruction of the two inner ears of wild-type adult zebrafish. Red: anterior semicircular canal; Blue: posterior semicircular canal; Green: lateral (horizontal) semicircular canal; Yellow: chambers housing the otoliths (utricle, saccule and lagena).

Technical Summary

Current projects in the Whitfield lab include:

Morphogenesis and patterning in the otic vesicle:

We are identifying pathways of gene activity that lead to correct axial patterning of the otic epithelium, including establishment of the otic neurogenic and sensory domains. We are also examining zebrafish lines that develop with morphological defects of the semicircular canal system and mild balance problems.

Modelling human deafness and vestibular disorders:

A number of our zebrafish lines form models for a variety of human diseases, including Waardenburg-Shah syndrome, Branchio-Oto-Renal syndrome and DiGeorge syndrome.

Regulation of endolymph production:

Both the volume and composition of the specialised fluid inside the ear, the endolymph, need to be tightly regulated for correct auditory and vestibular function. Our results indicate that the regulation of endolymph production in the zebrafish has many similarities with that in the mammal, including the development of the endolymphatic duct, and the functional conservation of gene products involved in endolymph homeostasis.

Chemically-induced hearing and vestibular impairment:

We are validating the zebrafish as a model for ototoxicity testing. We also aim to identify new compounds that can influence endolymph composition and volume in the ear.

Evolution of otic patterning:

We are comparing genetic mechanisms of otic development in the zebrafish with those in the lamprey, an agnathan vertebrate, and those in mammals, in order to understand key genetic events that led to changes in otic patterning during evolution.