Flagellar dynamics in the Volvocales and the emergence of coordination.

The properties of cells, and their interactions, are the result of a long and intricate evolutionary process of adaptation to the environment. As much of this selective pressure has a physical origin, the question arises of how the constraints imposed by physics influence the development of life forms. At the cellular level, the flagellum, a 10-20 micrometres long hair-like organelle highly conserved across eukaryotic species, is arguably one of the best examples of direct interaction between a cell and its environment. Indeed, the shape and beating pattern of flagella in unicellular eukaryotes have evolved to satisfy the peculiar requirements of locomotion at low Reynolds number, and the resulting swimming behaviour may have been selected to minimize the rate of encounter with predators. In multicellular organisms, the motion of large groups of flagella can have a direct impact on the extracellular environment by creating macroscopic flows which are responsible for tasks including fluid transport in the respiratory system, and breaking embryonic left-right symmetry. These flows may have also played a role in the development of multicellularity. Coordination among different flagella is often of paramount importance to perform these functions successfully. An emerging hypothesis is that coordination results from hydrodynamic interactions, yet there is very little direct experimental test of this possibility. The proposal focuses on the issue of flagellar dynamics and coordination in the Volvocales, an order of green algae. This group includes a variety of closely related species, from the unicellular biflagellate Chlamydomonas reinhardtii, the preferred model organism for biological studies of the eukaryotic flagellum, up to large multicellular spheroidal colonies, like Volvox carteri, with an external layer of thousands of somatic cells, responsible for locomotion. Despite their complex phylogenetic history, species in this group have fundamentally identical flagellar apparatuses, which allows a direct comparison of their beating dynamics. Our preliminary observations reveal that, despite the absence of any direct intercellular connections, the beating dynamics of different somatic cells in V. carteri is remarkably coordinated, and gives rise to a wave-like beating pattern that travels from the front to the back of the colony. This proposal aims at studying how such large scale coordination emerges from the behaviour of a single cell, with a particular focus on characterizing changes in flagellar dynamics in presence of an external mechanical stress, and the intracellular signals that cause these changes. V. carteri, with well separated somatic cells which can be isolated from the colony and studied individually, and C. reinhardtii, which is at the centre of biological research on eukaryotic flagella, are ideally suited to address this problem. The study of flagellar dynamics in the Volvocales represents a great opportunity to unravel some of the most fundamental aspects of the dynamics of the eukaryotic flagellum.

The most immediate beneficiaries of the proposed project will be other researchers. In biophysics and applied mathematics, the results will contribute to studies of flagellar dynamics, interflagellar synchronisation, and swimming of microorganisms. This research is almost exclusively based on theoretical models and simulations, and will greatly benefit from the comparison with detailed experimental results. This is especially true in the study of long range coordination, usually observed in organisms or tissues where visualisation of individual flagella is difficult. By studying coordination of flagella both from the same cell, and from different cells, this research will advance our knowledge of the interplay between mechanical forces and biochemical signalling, which will be of interest to the wide community working on synchronisation in coupled dynamical systems. In biology, the research will be immediately relevant to the large community studying C. reinhardtii, the principal model organism in molecular and cell biology for studies of flagellar motility. Because flagella are highly conserved across eukaryotic species, and are involved in many different tasks, the results will also be of interest to the general field that studies eukaryotic flagella and cilia (shorter than but structurally identical to flagella). Through the study of the connections between flagellar motility and intracellular calcium, the project will contribute to unravel the roles of calcium channels. This will have an immediate impact in the field of cell signalling, and it may contribute to understand the evolution of land plants. The collaboration with Dr. Glen Wheeler, an expert in intracellular calcium signalling in algae, will be fundamental to the success of the project. Our collaboration will help the development of quantitative approaches to biology, and the growth of biophysics in general, which in turn will contribute to increase UK's general competitiveness in science and technology. The project will also benefit the broader community outside academia. As cilia and flagella are present in virtually every cell in the human body, and serve a wide variety of functions, this project's findings could be of medical importance. In particular, results on motility regulation may help understand the origin of ciliopathies, genetic disorders which cause several serious syndromes in humans. Research on flagellar dynamics and regulation may ultimately benefit also industries associated with agriculture and aquaculture, as many higher plants and animals have gametes that rely on flagellar propulsion for fertilisation. Finally, the project may help devise methods to actively regulate algal motility in response to fluid flows in bioreactors. This could have an impact on the development of cost effective algal-based biofuels and carbon sequestration technologies, two areas at the center of UK's technological efforts. Effective dissemination of scientific results will be guaranteed through publications in high impact scientific journals, and the participation to national and international conferences. The University will also ensure dissemination to the wider public through its many knowledge transfer activities.