The Bird Lab is interested in how myosin molecular motors generate force on actin filaments and how defects in this fundamental cytoskeletal mechanism cause human disease. Dr. Bird studies this question using hair cells, the neural receptors for hearing and balance that are found within the inner ear.
Hair cells transduce sounds and accelerations using actin-based stereocilia that protrude from their surface. The loss of stereocilia and hair cells, due to noise exposure, ototoxic drugs and aging, is a significant cause of permanent hearing impairment that is estimated to affect more than 360 million people worldwide (1).
Myosin motors are critical for hair cell sensory transduction, with mutations in no fewer than six classes of myosin genes (I, II, III, VI, VII & XV) causing hearing loss. Using a multi-disciplinary approach, the Bird Lab is investigating how myosin motors regulate molecular trafficking within stereocilia and how this ultimately controls actin dynamics and stereocilia architecture.
The lab combines data from experiments with mutant animal models, cutting-edge microscopy in live cells, and purified proteins in biochemical and single molecule assays. These studies are expected to reveal the detailed mechanisms for how stereocilia mechanosensors are assembled and maintained, and they will inform the wider goal to therapeutically enhance repair processes to promote healthy, lifelong hearing.
- Mauriac SA, Hien YE, Bird JE, Carvalho SD, Peyroutou R, Lee SC, Moreau MM, Blanc JM, Geyser A, Medina C, Thoumine O, Beer-Hammer S, Friedman TB, Rüttiger L, Forge A, Nürnberg B, Sans N, Montcouquiol M. Defective Gpsm2/Gα(i3) signalling
disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome. Nat Commun. 2017 Apr 7;8:14907. doi: 10.1038/ncomms14907.
- Bird JE, Barzik M, Drummond MC, Sutton DC, Goodman SM, Morozko EL, Cole SM, Boukhvalova AK, Skidmore J, Syam D, Wilson EA, Fitzgerald T, Rehman AU, Martin DM, Boger ET, Belyantseva IA, Friedman TB. Harnessing molecular motors for nanoscale pulldown in live cells. Mol Biol Cell. 2017 Feb 1;28(3):463-475. doi: 10.1091/mbc.E16-08-0583. Epub 2016 Dec 8.
- Rehman AU, Bird JE, Faridi R, Shahzad M, Shah S, Lee K, Khan SN, Imtiaz A, Ahmed ZM, Riazuddin S, Santos-Cortez RL, Ahmad W, Leal SM, Riazuddin S, Friedman TB. Mutational Spectrum of MYO15A and the Molecular Mechanisms of DFNB3 Human Deafness. Hum Mutat. 2016 Oct;37(10):991-1003. doi: 10.1002/humu.23042. Epub 2016 Aug 21.
- Brewer CC, Zalewski CK, King KA, Zobay O, Riley A, Ferguson MA, Bird JE, McCabe MM, Hood LJ, Drayna D, Griffith AJ, Morell RJ, Friedman TB, Moore DR. Heritability of non-speech auditory processing skills. Eur J Hum Genet. 2016 Aug;24(8):1137-44. doi: 10.1038/ejhg.2015.277. Epub 2016 Feb 17.
- Fang Q, Indzhykulian AA, Mustapha M, Riordan GP, Dolan DF, Friedman TB, Belyantseva IA, Frolenkov GI, Camper SA, Bird JE. The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing. Elife. 2015 Aug 24;4. doi: 10.7554/eLife.08627.
- Drummond MC, Barzik M, Bird JE, Zhang DS, Lechene CP, Corey DP, Cunningham LL, Friedman TB. Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear. Nat Commun. 2015 Apr 21;6:6873. doi: 10.1038/ncomms7873.
- Bird JE, Takagi Y, Billington N, Strub MP, Sellers JR, Friedman TB. Chaperone-enhanced purification of unconventional myosin 15, a molecular motor specialized for stereocilia protein trafficking. Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12390-5. doi: 10.1073/pnas.1409459111. Epub 2014 Aug 11.