Cilia (also termed flagella) are microtubule-based protrusions of the plasma membrane that are central to many biological processes, including motility, sensing and development. Cilium and flagellum have become interchangeable terms and both have three distinct domains defined by the arrangement of their microtubules: the basal body that is embedded in the cytoplasm, the axoneme that protrudes from the cell body, and the transition zone (TZ) that links the two.
The axonemes of most motile flagella contain a central pair of microtubules that extend from the TZ and are essential for flagellar beating; defects in the central pair cause the human pathologies hydrocephalus and primary ciliary dyskinesia. Further, in recent years the TZ has emerged as central to ciliary function and it is a ‘hotspot’ for many of the proteins and complexes that are implicated in ciliary diseases (ciliopathies), such as retinal and kidney abnormalities.
The flagellum is also central to cell structure and pathogenicity in trypanosomatid parasites. These include African trypanosomes (causes African Sleeping Sickness), American trypanosomes (causes Chagas disease) and Leishmania (causes Leishmaniasis). Motility and flagellum function are critical for the ability of these parasites to spread and cause human and cattle disease.
African trypanosomes have genetic tools and resources that rival that of any model system. This means that trypanosomes are the ideal system to address important and ambitious research questions. My lab uses trypanosomes because of their importance as pathogens and also as a model system for understanding eukaryotic biology. We also use cultured mammalian cells for comparative evolutionary cell biology and because of their relevance to human biology and genetic diseases.
We focus on the function of the TZ in trypanosome and human flagellum biology and use this to increase our understanding of fundamental biology and disease.
1. Dean, S., Moreira-Leite, F., and Gull, K (2019) Basalin is an evolutionarily unconstrained protein revealed via a conserved role in flagellum basal plate function. eLife 8:e42282
2. Dean, S., Sunter, J. and Wheeler, S. (2016) TrypTag.org: Genome-wide protein localisation in the trypanosome. Trends in Parasitology 33(2), 80-82. DOI:https://doi.org/10.1016/j.pt.2016.10.009
Dean, S., Moreira-Leite, F., Varga, V. and Gull, K. (2016) Cilium transition zone proteome reveals compartmentalisation and differential dynamics of ciliopathy complexes. Proc Natl Acad Sci USA 113(35) E5135-E5143. https://doi.org/10.1073/pnas.1604258113
3. Dean, S., Gould, M., Dewar, C. and Schnaufer, A. (2013) Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes. Proc Natl Acad Sci USA 110(36):14741-6 https://doi.org/10.1073/pnas.1305404110
Dean S., Marchetti R., Kirk K. and Matthews K. (2009) A surface transporter family conveys the differentiation signal in African trypanosomes. Nature 459:213-217. https://doi.org/10.1038/nature07997