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postdoc/JRF, University of Cambridge


Absent a brain, how do microorganisms coordinate microscale appendages for diverse swimming gaits?

My research primarily concerns the motility of microorganisms and the biophysics of micro-swimming. The slender propulsion-generating appendages used by free-living eukaryotes for the purposes of swimming are structurally, morphologically, and behaviourally similar to the epithelial cilia that are at this very moment pumping physiological flows inside the human body. Consequently, the very same physical theory, namely one of “creeping” or “low-Reynolds number” flows in which viscous forces are dominant over inertial forces, can be used to elucidate the active dynamics.

One key mystery concerns the origins of ciliary or flagellar coordination: after all, there can be little benefit in having multiple flagella if you cannot coordinate them effectively (think three-legged races)… We sought to address this question using species of flagellate algae as our preferred model system. These span several orders of magnitude in size and flagella number, which allow us to reveal a fascinating balance between active biological control and passive physical interactions that changes or evolves with increasing system size or complexity.

For instance, the stereotypical biflagellate alga Chlamydomonas actuates two nearly- identical flagella in unison in a breaststroke gait, while the large spherical alga Volvox rotates through the fluid using thousands of surface attached flagella which beat metachronously. In the latter, neighbouring flagella interact directly through the fluid, so no centralised control is necessary for spontaneous emergence of waves, much like the rise and fall of hands in a stadium. Species that have precisely four flagella can even produce locomotion patterns that resemble the trotting, galloping, pronking gaits of horses and other quadrupeds.

Disruption or mutation of ciliary coordination can not only result in reduced swimming and navigational efficacy in algae, but moreover in complex syndromes or ciliopathies in mammals. Such ciliopathies can have further downstream consequences including blindness, obesity and kidney disease.


Lag, lock, sync, slip: the many 'phases' of coupled flagella.

Abstract: In a multitude of life's processes, cilia and flagella are found indispensable. Recently, the biflagellated chlorophyte alga Chlamydomonas has become a model organism for the study of ciliary motility and synchronization. Here, we use high-speed, high-resolution imaging of single pipette-held cells to quantify the rich dynamics exhibited by their flagella. Underlying this variability in behaviour are biological dissimilarities between the two flagella-termed cis and trans, with respect to a unique eyespot. With emphasis on the wild-type, we derive limit cycles and phase parametrizations for self-sustained flagellar oscillations from digitally tracked flagellar waveforms. Characterizing interflagellar phase synchrony via a simple model of coupled oscillators with noise, we find that during the canonical swimming breaststroke the cis flagellum is consistently phase-lagged relative to, while remaining robustly phase-locked with, the trans flagellum. Transient loss of synchrony, or phase slippage, may be triggered stochastically, in which the trans flagellum transitions to a second mode of beating with attenuated beat envelope and increased frequency. Further, exploiting this alga's ability for flagellar regeneration, we mechanically induced removal of one or the other flagellum of the same cell to reveal a striking disparity between the beatings of the cis and trans flagella, in isolation. These results are evaluated in the context of the dynamic coordination of Chlamydomonas flagella.

Pub.: 28 Feb '14, Pinned: 25 Jun '17

Analysis of unstable modes distinguishes mathematical models of flagellar motion.

Abstract: The mechanisms underlying the coordinated beating of cilia and flagella remain incompletely understood despite the fundamental importance of these organelles. The axoneme (the cytoskeletal structure of cilia and flagella) consists of microtubule doublets connected by passive and active elements. The motor protein dynein is known to drive active bending, but dynein activity must be regulated to generate oscillatory, propulsive waveforms. Mathematical models of flagellar motion generate quantitative predictions that can be analysed to test hypotheses concerning dynein regulation. One approach has been to seek periodic solutions to the linearized equations of motion. However, models may simultaneously exhibit both periodic and unstable modes. Here, we investigate the emergence and coexistence of unstable and periodic modes in three mathematical models of flagellar motion, each based on a different dynein regulation hypothesis: (i) sliding control; (ii) curvature control and (iii) control by interdoublet separation (the 'geometric clutch' (GC)). The unstable modes predicted by each model are used to critically evaluate the underlying hypothesis. In particular, models of flagella with 'sliding-controlled' dynein activity admit unstable modes with non-propulsive, retrograde (tip-to-base) propagation, sometimes at the same parameter values that lead to periodic, propulsive modes. In the presence of these retrograde unstable modes, stable or periodic modes have little influence. In contrast, unstable modes of the GC model exhibit switching at the base and propulsive base-to-tip propagation.

Pub.: 04 Apr '15, Pinned: 25 Jun '17

Coordinated beating of algal flagella is mediated by basal coupling

Abstract: Cilia and flagella often exhibit synchronized behavior; this includes phase locking, as seen in Chlamydomonas, and metachronal wave formation in the respiratory cilia of higher organisms. Since the observations by Gray and Rothschild of phase synchrony of nearby swimming spermatozoa, it has been a working hypothesis that synchrony arises from hydrodynamic interactions between beating filaments. Recent work on the dynamics of physically separated pairs of flagella isolated from the multicellular alga Volvox has shown that hydrodynamic coupling alone is sufficient to produce synchrony. However, the situation is more complex in unicellular organisms bearing few flagella. We show that flagella of Chlamydomonas mutants deficient in filamentary connections between basal bodies display markedly different synchronization from the wild type. We perform micromanipulation on configurations of flagella and conclude that a mechanism, internal to the cell, must provide an additional flagellar coupling. In naturally occurring species with 4, 8, or even 16 flagella, we find diverse symmetries of basal body positioning and of the flagellar apparatus that are coincident with specific gaits of flagellar actuation, suggesting that it is a competition between intracellular coupling and hydrodynamic interactions that ultimately determines the precise form of flagellar coordination in unicellular algae.

Pub.: 02 May '16, Pinned: 24 Jun '17