The flagellum/cilium of mammalian cells in health and disease

Mucociliary clearance of the respiratory tract by epithelial cell cilia is an important defence mechanism against inhaled pathogens, for instance Bordetella pertussis colonizes the cilia of the mammalian respiratory epithelium, recognising cryptic receptors on cilia surfaces. Defective mucociliary clearance in the respiratory tract leads to recurrent infections by many agents. Ciliary defects may be either congenital or acquired secondarily due to infection, toxins, smoking or drugs. Patients with a group of recessive, inherited disorders (primary ciliary dyskinesia, PCD) possess abnormal ciliary activity, absent mucociliary transport, abnormal ciliary ultrastructure and in Kartagener's syndrome patients exhibit situs inversus where the heart is transposed to the right side of the chest, and the internal abdominal organs may also be transposed. The tracheal cell layer is an ordered, polarised epithelium whereby cells in basal regions initiate a differentiation and multiple centrioles are produced in the apical cytoplasm and then migrate to the plasma membrane facing the lumen of the trachea where they nucleate cilia.

We are studying the proteome of mammalian cilia and contrasting this with the proteome of the trypanosome flagellum. In addition we are using the very tractable reverse genetics of trypanosomes to study the function of conserved proteins of both human cilia and trypanosome flagella.