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Moving around without a brain: Evolution of basal cognition in single-celled organisms

Periodic Reporting for period 2 - EvoMotion (Moving around without a brain: Evolution of basal cognition in single-celled organisms)

Reporting period: 2021-09-01 to 2023-02-28

How is complex behaviour encoded in single-cell organisms? This has been a deep mystery since the early days of microscopy hundreds of years ago, when the movement patterns of diverse microscopic eukaryotes were observed and recorded for the first time (usually through hand-drawn sketches). More recently, research efforts aimed at understanding the generation and control of behaving organisms has been focused almost exclusively on metazoa – particularly model vertebrate species, yet neglecting the evolutionary origins of these diverse behaviours, namely the unicellular organisms.

This ERC project EvoMotion seeks to address the fundamental question of how simple organisms control and modify their behavioural and motor actions in response to dynamic environmental cues. This work will yield important insights into how these strategies diversified and evolved in more complex multicellular forms of life. Through this targeted interdisciplinary exploration, we hope to obtain insights into the origins of biological cognition itself, advocating for the redefinition and extension of so-called ‘basal’ or ‘minimally-cognitive’ systems down to the unicellular scale.

Our primary objectives in EvoMotion are to
- Develop novel strategies to characterize and model movement and behaviour at the microscopic scale. This is associated with unique challenges of working with small, usually rapidly deforming microorganisms. We construct novel and integrated experimental assays of behaviour (making both intracellular and external measurements) using state-of-the-art technology emphasizing controllability using microfluidics and other forms of flow and physical cell manipulation.
- Establish objective and mathematical measures of micro-organismal motility and behaviour that can be applied across diverse species and even scales, with emphasis on motility arising through coordinated ciliary actuation and fluid dynamical modelling.
- Create a new class of macroscopic self-powered robots modelled on these extant microscopic organisms, as a means to understand the biomechanics and strategies of underwater propulsion, with possible future applications in informing the design of remotely controlled devices designed to operate in viscous environments.
In relation to the overarching themes and objectives of EvoMotion, PI Dr Wan published a 24-page perspective/concept article entitled ‘Origins of eukaryotic excitability’ (Wan & Jekely, 2021), as part of a major 2-part series in the journal Philosophical Transactions of the Royal Society B on basal cognition across the tree of life from bacteria to single-celled eukaryotes, all the way to animals. This work, conceived during the first covid lockdown period in the UK, proposes a new conceptual framework against which eukaryotic behaviour can be assessed, identifying key cellular innovations associated with eukaryogenesis, particularly the role of cell size – ability for the cell to overcome rotational diffusion and achieve deterministic trajectories, the role of cilia – an importance and ubiquitous organelle that enables finer structural and dynamic control, and the role of bioelectrical signalling – a means by which rapid sensory and motor cues can be transduced or enacted. This work has already received 30 citations and is now regularly used as a teaching resource.

On ciliary coordination and whole-organism navigation, we have made significant progress in developing data-driven models of self-propelled microswimmers, with particular focus on the model single-celled eukaryote Chlamydomonas reinhardtii and the mechanisms of active biciliary coordination. The modelling efforts are led by PDRA Dr Cortese and PI Wan, and has resulted in a number of publications (Cortese & Wan PRL 2021, Cortse & Wan 2022 biorxiv preprint, and Guo et al, J.Roy.Soc. Interface 2021). Our 2021 paper entitled ‘control of helical navigation by three-dimensional flagellar beating’ explained the biomechanical origin of the corkscrewing swimming motion for the first time, and received an editors’ suggestion in the journal Physical Review Letters.

In another study, co-led by project members Bentley and Laeverenz-Schlogelhofer and supervised by PI Wan, we present a novel droplet microfluidics-based assay for comprehensively phenotyping microswimmer movement at the single-cell level (including trajectory history and probability fluxes) in response to a variety of controlled physical, photo, and chemical cues. This major study was accepted and is now in press at the journal eLife, scheduled for publication later this month.

We have also published our first paper on roboflagellates (Diaz et al, 2021) – macroscopic robotic models of quadriflagellate microswimmers, in collaboration with our US collaborators. This first proof-of-principle design demonstrates feasibility, we are now extending this control architecture to model directional response such as phototaxis. In relation to diatom motility we have made significant progress in phenotyping the movement of diverse species, the first paper associated with this is currently being prepared by PDRF Bondoc-Naumovitz. New experimental and computational expertise developed directly as part of EvoMotion are currently being used in new collaborations that have unexpected become possible. PhD student Poon led our new paper on the cilia-driven movement of coral larvae (Poon et al, biorxiv preprint 2022).

In terms of dissemination of research results at conferences, in the first year the team gave a total of around 20 virtual presentations at national and international conferences, and invited seminars. Since the resumption of in-person meetings/travel, the team has given >30 further talks, ensuring that our results are widely disseminated and in a timely manner. PI Wan also secured a 3-month Eleonore-Trefftz Visiting Professorship to TU Dresden to explore collaborations related to EvoMotion.
We are currently progressing on several complementary fronts, guided by the aims and objectives of the Scientific proposal. In relation to behavioural phenotyping and testing the cognitive limits of single cells, we are now applying the innovations and concepts developed in our eLife paper to more complex behavioural scenarios. These observations and recordings made at the individual level contrasts from traditional approaches in which behaviour is recorded in bulk and allows us to target long-term or adaptive behavioural responses to environmental conditions in a more controlled manner than previously possible. For example, we can track fast single-cell responses to chemical perturbations that are delivered in real-time, greatly improving our resolution in terms of response specificity.

Concurrently, we have built a fully-functional custom apparatus to measure bioelectrical activity inside living, motile cells at the same time as taking high-speed, high-resolution measurements. This integrated approach linking signalling to behaviour is the ‘holy grail’ in the field, and is led by PDRA Laeverenz-Schlogelhofer who will present this work for the first time at the upcoming American Physical Society March meeting in 2023. The first paper is under preparation. Multiple projects are now anticipated to derive from this new measurement capability.

We continue to develop more sophisticated robotic realisations of the biological microswimmers, based on our initial proof-of-concept design. To our knowledge no similar models exist, and approach to using the robots to help us understand the biological origins of ciliary coordination, is unique. Related to this, our PhD student Poon will be paying an extended visit to our collaborator’s lab in the US next year.

Finally, as indication of the global attention already received by the project, the group has been invited to write a number of reviews on disparate topics in EvoMotion, all to appear in the next year in different interdisciplinary journals. This includes an article on morphological computation embodiment by ciliated organisms (single author paper by PI Wan), a second on the approaches and challenges of studying motility at the microscale, and a third on the origins and control of ciliary metachronism.