EPSRC DTP PhD studentship: Devising Novel Measures of Ciliary and Flagellar Activity

University of Exeter - College of Engineering, Mathematics and Physical Sciences

Main supervisor: Dr. Kirsty Y. Wan (University of Exeter)
Co-supervisor:  Prof. John R. Terry (University of Exeter)

Project Description:

What is it that we humans share with the humble pond scum? The answer turns out to be our cilia — those tiny versatile hair-like protrusions attached to cells. Cilia (interchangeably called flagella) are inextricably involved in many of life’s sensory processes including cellular responses to hormones, the propulsion of sperm, and the swimming of free-living micro-algae in our ponds and gardens [1].

Recent years have seen a surge of interest in the structure and biology of cilia. The question of what constitutes “normal” ciliary function is a pressing and prescient issue for the 1 in 1000 people affected by diseases linked to ciliary dysfunction, which cause kidney cysts, blindness, deafness, infertility and more [2]. Consequently, there is increasing demand for mathematical or quantitative methodologies to provide novel insights to further our understanding of ciliary behaviour. These noisy, active and highly-sensitive organelles also exist out of equilibrium — an added complexity that renders them more interesting systems to model and analyse.

Motivated by the discovery that algal flagella exhibit correlated fluctuations reminiscent of human heartbeat dynamics [3], this project will begin by investigating how flagellar beating in a model green alga is modified by environmental perturbations or mutagenesis. The emphasis will be on extracting maximal spatiotemporal information from high-speed live imaging data, and making novel use of fluid mechanics, elasticity, geometry and dynamical systems theory to elucidate any resulting changes to the beating dynamics. One key aim is to harness the power of mathematics to identify, interpret, and model the observed morphological variability, and thereby contribute to developing a novel diagnostic platform to discriminate between normal and pathological modes of ciliary/flagellar beating. This will be tested on algal flagella in the first instance, and if successful, provide a robust and reliable measure of abnormal ciliary activity that will ultimately be made applicable to mammalian ciliopathies.

The EPRSC-DTP funded student will be based in Exeter’s brand new interdisciplinary Living Systems Institute, and will have a unique and exciting opportunity to engage in cutting-edge research and collaborations that go beyond traditional subject boundaries. The student is expected to develop and participate in experimental work that will complement the theoretical aspects of this project.

[1] K.Y. Wan & R.E. Goldstein (2016), Coordinated beating of algal flagella is mediated by basal coupling, Proc. Nat. Acad. Sci. USA (113) E2784-93

[2] I. Ibańez-Tallon, N. Heintz, H. Omran (2003), To beat or not to beat: roles of cilia in development and disease, Hum. Mol. Gen. (12) R27-35

[3] K.Y. Wan & R.E. Goldstein (2014), Rhythmicity, recurrence, and recovery of flagellar beating, Phys. Rev. Lett. (113) 238103

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South West England