Project ID CM-HD2024_01

ThemeCM-HD

Co Supervisor 1A Faculty of Dentistry, Oral & Craniofacial Sciences, Centre for Craniofacial & Regenerative BiologyWebsite

Co Supervisor 1B Faculty of Dentistry, Oral & Craniofacial Sciences, Centre for Craniofacial & Regenerative BiologyWebsite

Integrating development, homeostasis and repair to enhance repair strategies for the ear drum

During development organs are formed from the integration of different tissues to produce a final complex structure. This is particularly true of the ear, where different tissues come together to create the external, middle and inner ear compartments. Signalling is essential to link up the parts of the ear into a chain for the transfer of sound. Defects in this process lead to conductive hearing loss, where sound fails to reach the inner ear (1 in 10,000 births).
Knowledge of the processes involved during ear development is important not only for understanding the underlying causes of congenital hearing loss, but also to provide the principles to recreate structures later in life. It can, therefore, inform our understanding of how to enhance repair of the ear.
This proposal aims to first address how the ear is integrated during development to create a functional organ, focusing on the intersection between the middle and external ear and the formation of the ear drum. The ear drum is unique in the body in that it is created from all three germ layers: ectoderm (& neural crest), mesoderm, and endoderm. An understanding of how these layers come together and interact in the embryo will then be used to assess how these different layers respond to injury and take part in repair of the adult ear drum.
Aim 1: To understand the signals that integrate the different parts of the ear during development
Aim 2: To use developmental knowledge to follow and enhance repair of the ear

Skills training: molecular biology techniques, mouse developmental biology, culturing, surgery, confocal imaging, stem cell biology, critical thinking, presentation and writing skills.

Year 1: Ear drum development in the mouse
Year 2: Injury and repair models
Year 3: Integration of development and repair mechanisms

Representative Publications

Thompson, H. Tucker , A.S. (2013). Dual origin of the epithelium of the middle ear. Science 339, 1453-1456. DOI: 10.1126/science.1232862 Tucker, A.S., Dyer, C.J., Romero, J.M.F., Teshima, T.H.N., Fuchs, J.C., Thompson, H. (2018). Mapping the distribution of stem/progenitor cells across the middle ear during homeostasis and inflammation. Development Jan 11; 145. pii: dev.154393. doi: 10.1242/dev.154393. PMID: 29217752. Fons, J.M., Mozaffari, M., Malik, D., Marshall, A.R., Connor, S., Greene, N.D.E., Tucker, A.S. (2020). Epithelial dynamics shed light on mechanisms underlying ear canal defects. Development Oct 22: dev.194654. PMID: 33093151. doi: 10.1242/dev.194654.
Developmental aspects of the tympanic membrane: Shedding light on function and disease. Mozaffari M, Jiang D, Tucker AS.Genesis. 2020 Mar;58(3-4):e23348. doi: 10.1002/dvg.23348. Epub 2019 Nov 25.PMID: 31763764 International Consensus Recommendations on Microtia, Aural Atresia and Functional Ear Reconstruction. Zhang TY, Bulstrode N, Chang KW, Cho YS, Frenzel H, Jiang D, Kesser BW, Siegert R, Triglia JM.J Int Adv Otol. 2019 Aug;15(2):204-208. doi: 10.5152/iao.2019.7383.PMID: 31418720 An alternative approach to mixed hearing loss in otosclerosis: stapes surgery combined with an active middle-ear implant. Powell HRF, Pai I, Ghulam H, Jiang D.J Laryngol Otol. 2018 May;132(5):457-460. doi: 10.1017/S0022215118000105.PMID: 29891017