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Living Systems Institute

If you would like to give an oral presentation, please ensure that you submit your abstracts by 17 Jan 2024, for consideration.

PoLNET Workshop - Biological filaments: Structure, dynamics, and function

Scientific organisers: Kirsty Wan and Bertram Daum.

Biological filaments are central to a plethora of biological processes, ranging from muscular activity at the macroscale to cellular motion at the microscale. A comprehensive understanding of their function requires cutting-edge approaches that transcend the traditional boundaries of science. This workshop aims to stimulate fresh conversations and forge new interdisciplinary networks between biologists and physicists aiming to elucidate the structure, dynamics, and function of biological filaments using diverse and state-of-the-art techniques. Bringing together world-leading experts, as well as ECRs from this broad and vibrant field, we aim to drive transformative discoveries into the underlying principles governing the diverse function of biological filaments as essential building blocks of life.

We are excited to announce a 2-day workshop entitled Biological filaments: Structure, dynamics, and function which will take place at the Living Systems Institute, University of Exeter, UK from Wednesday 31 of January 2024 to Thursday 1 of February 2024.

The aim of this workshop is to foster a network of physicists and biologists researching biological filaments across scales and from different conceptual, technical, and disciplinary angles.

Confirmed speakers:

Sonja-Verena Albers (University of Freiburg, D)
Morgan Beeby (Imperial College, London, UK)
Alexandra Brand (University of Exeter, UK)
Mack Durham (University of Sheffield, UK)
Benjamin Friedrich (Technical University of Dresden, D)
Vicki Gold (University of Exeter, UK)
Eric Keaveny (Imperial College London, UK)
Marco Mazza (Loughborough University, UK)
Danielle Paul (University of Bristol, UK)
Mitya Pushkin (University of York, UK)
Orkun Soyer (University of Warwick, UK)

Wednesday 31st Jan 2024 

9:30 -  Welcome by Kirsty and Bertram  

Session 1 – Structure and function of bacterial and archaeal filaments  

9:40 - Vicki Gold, University of Exeter - A new twist on bacterial type IV pili 

10:00 - Sonja-Verena Albers, University of Freiburg, Germany - Structure and function of archaeal cell surface filaments 

10:20 - Matt Gaines, University of Exeter - CryoEM of motile and biofilm-forming archaeal surface filaments  

10:35 - Coffee break

11:00 - Morgan Beeby, Imperial College London - Three stories about evolution of biological filaments as propellers 

11:20 Marcus Taylor, MPI for Infection Biology - The Super-molecular machines of the innate immune system: understanding how they work to building new ones

11:35 - Panel discussion

12:00 - Lunch  

Session 2 – Dynamics and coordination of swimming filaments 

12:50 Michael Gomez, King’s College London - Twist dynamics of bacterial flagella

13:05 Eric Keaveny, Imperial College London - Coordinated motion of active filaments

13:25 Benjamin Friedrich, TU Dresden, Germany - Synchronization of cilia and flagella

13:45 John Severn, University of Cambridge - Modal analysis and optimisation of swimming active filaments

14:00 Maria Tatulea-Codrean, University of Cambridge - Swimming with bacterial flagella: too many cooks spoil the broth

14:15 Panel discussion

14:40 Coffee break + Group photo

Session 3 – Future Strategy of PoLNet and the role of ‘disruptive’ research 

15:00 – 16:15 -  Mark Leake, University of York  

16:15 – 18:00 -  Poster Session with wine and nibbles  

19:00 - Dinner at Southgate Hotel  

Thursday 1st Feb 2024 

Session 4 – Surface-based motility 

9:30 - Mack Durham, University of Sheffield - Bacteria use chemical and mechanical stimuli to guide pili-based motility across surfaces

9:50 - Marco G. Mazza, Loughborough University - Gliding motility of filamentous bacteria  

10:10 - Hannah Laeverenz-Schlogelhofer, University of Exeter - Bioelectric control of ciliary dynamics in a walking single cell.

10:25 - Orkun S. Soyer, University of Warwick - Dynamics of gliding motility in a filamentous cyanobacterium  

10:45 - Panel discussion 

11:10 - Coffee break 

Session 5 – Group activity: defining the grand challenges in the field 

11:30 – 12:20  

12:20 - Lunch 

Session 6 – Filaments in multicellular systems 

13:15 - Danielle Paul, University of Bristol - Nature’s own coaxial cable  

13:35 - Mitya Pushkin, University of York - The chiral core of the collagen microfibril

13:55 - Isabella Guido, University of Surrey - Cytoskeletal active networks under external mechanical stimulation.

14:10 - Coffee break

14:30 - Anders Aufderhorst-Roberts, University of Durham - A cell-free approach to remodel and mechanically probe intermediate filament networks

14:45 -  Alexandra Brand, University of Exeter - Penetrative filamentous growth behaviours of the fungal pathogen, Candida albicans 

15:05 - Panel discussion 

Wrap up and end 

15:30 - Kirsty and Bertram Closing remarks and best poster prize. 

 

 

 

Vicki Gold, University of Exeter - A new twist on bacterial type IV pili 

Type IV pili (T4P) are protein filaments found on the surface of many bacteria. The filaments play a critical role in various cellular functions including adhesion, motility and DNA uptake. T4P represent an important area of research due to their role in biofilm formation and pathogenesis. Due to the multi-functional nature of T4P, it has historically been difficult to delineate filament properties that allow for specific function. We discovered that the model organism Thermus thermophilus assembles two different T4P, which presents an opportunity to investigate the unique properties of each filament in relation to the important roles they play in the cell. We used cryoEM to determine high-resolution structures of the two Thermus T4P, conducted molecular dynamics simulations to investigate their physical properties, and correlated this to functional assays to investigate the roles of the two filaments. Such exploration of T4P offers potential avenues for advancing medical and biotechnological innovations against bacterial challenges. 

Sonja-Verena Albers, University of Freiburg, Germany - Structure and function of archaeal cell surface filaments 

Archaea assemble many cell surface structures that are important for interacting with the environment on their cell surface. These can be type IV pili, the archaellum, or threads. In this talk, I will discuss how a selected number of these are assembled, their structure, and for which purpose they are employed. 

Morgan Beeby, Imperial College London - Three stories about evolution of biological filaments as propellers 

Cell motility has enormous selective benefit. Curiously, microbes from all three domains of life have independently evolved molecular propellers from biological filaments. Our lab is interested in using these propellers as case studies to understand how molecular machines evolve. I will describe three short stories about how filaments have evolved in which we have used 3-D in situ electron microscopy imaging to gain insights into evolution from the perspective of molecular structure. First, I will discuss how bacterial flagellar filaments, best know as whip-like appendages to model organisms such as Escherichia coli or Salmonella, have evolved more elaborate structures in bacteria who position their flagellar at their cell poles. Specifically, I will discuss the polar flagellate Campylobacter jejuni, which has evolved a shorter and more rigid flagellum more evocative of a corkscrew than a whip, and whose flagellum has co-evolved with its cell shape and flagellar motor. Second, I will describe how other species have evolved unusually large flagella. Finally, I will describe how the analogous archaella molecular propeller, the archaellum, co-opted part of a biological filament to serve an essential component when it first evolved propeller functionality. In all cases, we see co-option of pre-existing structures and functions for novel or adapted roles. 

Eric Keaveny, Imperial College London - Coordinated motion of active filaments 

Active filaments – self-actuated, slender, flexible bodies – are fundamental to fluid transport and propulsion in and around the cells to which they are attached. Often these filaments work in concert, producing intricate, spatiotemporal patterns with a prime example being metachronal waves exhibited by cilia arrays. In this talk, I will examine filament coordination for two different active filament models, one where filament beating arises dynamically through a buckling instability, and another where filament motion is linked to a dynamic phase variable that controls its evolution through a set sequence of shapes. In both cases, I will explore the effect of the underlying surface on the coordinated state, focusing both on surface topology and whether the surface is free to move or held fixed. In doing so, we will see that these two surface conditions can conspire to drastically alter the coordinated state, ultimately affecting the filament-driven fluid transport. 

Benjamin Friedrich, TU Dresden, Germany - Synchronization of cilia and flagella 

In this talk, I will first briefly review what we learned from microorganisms such as the bi-flagellate green alga Chlamydomonas on the physics of synchronization: how we can characterize each beating cilium as a noisy biological oscillator that slows down when its hydrodynamic load increases and how this load response facilitates synchronization by hydro-mechanical coupling [1]. I will then show how we can leverage this knowledge to understand tissue-scale synchronization in cilia carpets [2]. Using a multi-scale computational model, we show how hydrodynamic interactions couple cilia and synchronize their beat, resulting in local but not global synchronization in the presence of noise. We discuss the impact of cilia synchronization in the form of metachronal coordination on the magnitude of fluid pumping (substantial) and its direction (marginal). Finally, together with the Jurisch-Yaksi lab (NTNU), we quantitatively identify and characterize such local synchronization in the ciliated epithelium of the zebrafish nose, which provides an ideal model system due to its conserved properties and ease of accessibility [3]. 

[1] V. F. Geyer, F. Jülicher, J. Howard, B. M. Friedrich: Cell-body rocking is a dominant mechanism for flagellar synchronization in a swimming alga, PNAS 110:18058–18063, 2013 [2] A. Solovev, B.M. Friedrich: Synchronization in cilia carpets: multiple metachronal waves are stable, but one wave dominates, New J Physics 24:013015, 2021 [3] C. Ringers, S. Bialonski, M. Ege, A. Solovev, J.N. Hansen, Inyoung Jeong, B.M. Friedrich, N. Jurisch-Yaksi: C. Ringers: Novel analytical tools reveal that local synchronization of cilia coincides with tissue-scale metachronal waves in zebrafish multiciliated epithelia, eLife 12:e77701, 2023 

Mack Durham, University of Sheffield - Bacteria use chemical and mechanical stimuli to guide pili-based motility across surfaces

Bacteria use chemical and mechanical stimuli to guide pili-based motility across surfaces Bacteria use tiny filamentous grappling hooks called pili to pull themselves across solid surfaces. While this form of motility is orders of magnitude slower than flagella-based motility, it allows cells in developing biofilms to both navigate chemical gradients and collectively spread across surfaces. In this talk, I will discuss our recent work that reveals how surface attached bacteria can use both chemical and mechanical stimuli to regulate pili-based motility. First, we demonstrate that surface attached bacteria directly sense chemical gradients across the length of their bodies to guide pili-based chemotaxis towards nutrients. This stands in sharp contrast to the temporal sensing mechanisms used by swimming bacteria and conclusively demonstrates that bacterial are not too small to make spatial measurements, as has been previously postulated. Second, we developed new tools to resolve the behaviour of individual cells in densely packed conditions, which reveals that cells actively sense the movement of their neighbours and use this information to move more efficiently as a group. These two new findings show that surface attached bacteria actively can sense and respond to stimuli in ways previously not thought possible.

Marco G. Mazza, Loughborough University - Gliding motility of filamentous bacteria 

Filamentous cyanobacteria can show fascinating examples of nonequilibrium self-organization, which are not yet well understood from a physical perspective. We investigate the motility and collective organization of colonies of these simple multicellular lifeforms. As their area density increases, linear chains of cells gliding on a substrate show a transition from an isotropic distribution to bundles of filaments arranged in a reticulate pattern. Based on our experimental observations of individual behaviour and pairwise interactions, we introduce a nonreciprocal model accounting for the filaments’ large aspect ratio, fluctuations in curvature, motility, and nematic interactions. This minimal model of active filaments recapitulates the observations and rationalizes the appearance of a characteristic length scale in the system, based on the Peclet number of the cyanobacteria filaments. 

Orkun S. Soyer, University of Warwick - Dynamics of gliding motility in a filamentous cyanobacterium 

Gliding motility is a specific type of bacterial motility that comprises a characteristic back-and-forth movement pattern and that does not involve flagella. This type of motility is always found to involve secretion of polysaccharides, known as slime, and in some single-celled bacteria, membrane proteins that seem to traverse the cell body in a helical fashion. In gliding filamentous cyanobacteria, where each filament consists of multiple cells that are connected to each other, it is unclear how gliding motility is coordinated across a filament. Here, I will present results from our ongoing work on characterising gliding motility dynamics in the filamentous cyanobacterium Fluctiforma draycotensis, a freshwater species. Using transmitted internal reflection microscopy (TIRF), we find that the cells present membrane protein clusters that have a specific fluorescence. Tracking these proteins reveals that movement of filaments involves a closely coupled translation and rotation, and that movement happens inside slime tubes rather than on a layer of slime. We find that reversals of direction, during each back-and-forth movement set, involve filaments coming close to a full stop. We characterise this ‘dwell time’, as well as the speed and direction of travel, by analysing many individual filaments using time-lapse fluorescent microscopy. The resulting dynamics can be explained by a physical model that implements cellular translational forces and mechano-sensing of external and internal forces by each cell. 

Danielle Paul, University of Bristol - Nature’s own coaxial cable 

Actin is the most abundant protein in eukaryotic cells, it can take a globular form or polymerise into a helical filament. It has a central role in the cell and critical to many functions including motility, maintenance of shape and muscle contraction. The importance of this biological filament cannot be understated. However, in 2020 we discovered a novel population of actin filaments residing within the lumen of another biological filament -the microtubule a cylindrical tube of tubulin dimers another crucial protein in the cytoskeleton or ‘cell scaffolding’. This arrangement of proteins, in a co-axial formation, had never been observed before and gives rise to many questions about assembly and function. We have recently observed microtubule luminal actin in human platelets, platelets are a very specialised cell type involved in blood clotting, but are these biological co-axial cables in all cells? 

Mitya Pushkin, University of York - The chiral core of the collagen microfibril

Collagen is by far the most abundant protein in ECM and human body. It accounts for 90% of bone matrix protein content. Being one of the main structural biomaterials, it organises, directs and affects a multitude of multicellular processes, from bone mineralisation to cancer cells invasions. The ability to form fibres, bundles of fibres, and intricate fibrillar matrices underlies its ubiquity. Despite its importance, the physical principles of organisation of even the most elementary of collagen fibrillar structures, the microfibril, remain unknown. We will discuss them in this talk.

Alexandra Brand, University of Exeter - Penetrative filamentous growth behaviours of the fungal pathogen, Candida albicans 

The majority of the three – four million species of fungi grow in a filamentous (hyphal) form. Fungal exert a huge influence in the biosphere, from breaking down organic matter, supporting plants and microbes through symbiotic relationships, and through the biomineralization of inorganic material. Fungi are non-motile eukaryotes so, to forage for nutrients, their filaments must maintain polarised growth while penetrating diverse substrates and responding to directional cues. We investigate hyphal growth behaviours in the opportunistic pathogen, Candida albicans, a ‘filamentous yeast’ where hypha formation leads to invasion of a wide range of host tissues, from kidneys to cartilage. The use of microfabricated chambers, live-cell imaging and molecular genetics has allowed us to identify changes in apical dominance, directional memory, ‘helical’ growth within high-density substrates and to quantify the tip force applied by these hyphae. Ultimately, disruption of these behaviours might offer a combinatorial therapy approach to prevent deep-seated infections.

 

Matt Gaines, University of Exeter - CryoEM of motile and biofilm-forming archaeal surface filaments  

Archaea represent the most adaptable kingdom of life, conquering the most extreme of niches and thriving within. Much of their success has been owed to the evolution of their filamentous structures, allowing for motility, adhesion, cell signalling. Using CryoEM, an in-depth analysis can be conducted to study the comparison between archaeal filaments of different species, with those of their ancestral bacterial species, to shed light on how this kingdom evolved to what it is today.

John Severn,  University of Cambridge - Modal analysis and optimisation of swimming active filaments

Active flexible filaments are the classical continuum framework used to model the locomotion of swimmers driven by the periodic oscillation of flagella, such as spermatozoa. The same model can be used to address the locomotion of artificial swimmers. Classical work on active flexible filaments has been devoted to quantifying the relationship between internal forcing (both localised or distributed internal moments or forces) and external output (especially filament shape and swimming speed). Posing locomotion mathematically as an optimisation problem, we reveal that the swimming of an isolated active filament is governed by the dynamics of four forcing eigenmodes, only two of which are independent. We then demonstrate how this modal approach can be used to optimise recently created artificial swimmers wherein polymeric filaments are periodically driven by cardiac cells (cardiomyocytes).

Maria Tatulea-Codrean,  University of Cambridge - Swimming with bacterial flagella: too many cooks spoil the broth

Peritrichous bacteria like the model organism Escherichia coli have a variable number of flagella which they use, amongst other things, for swimming. What sets the number of flagella and could this be related to the motility of the cell? As the flagellar number is more easily controlled in silico than in vivo, we revisit this open question using slender-body theory simulations to quantify the hydrodynamic interactions between nearby flagella. In our model, we also incorporate the full torque-speed relation of the bacterial flagellar motor (BFM), in contrast to previous studies which assume the BFM operates at a constant torque. By coupling the dynamics of flagellar motors and filaments, we find that the torque-generating capacity of the BFM plays a crucial role in the overall swimming of the cell.

Michael Gomez, King’s College London - Twist dynamics of bacterial flagella

Bacteria swim in viscous fluid by rotating slender elastic organelles (flagella). While the steady rotation of a helical filament represents a classic problem in bacterial locomotion, the dynamic process by which a flagellum reaches a state of uniform rotation, following a change in motor speed, is much less understood. Here we present an 'effective-column' model for the flagellar filament, which replaces its helical geometry with a naturally-straight rod whose extensional and torsional deformations are coupled. The advantage of this model is that it may readily be combined with resistive-force theory, to predict the time-dependent hydrodynamic loads and swimming speed resulting from a spatially-varying rotation rate. We then extend our model to incorporate twist-induced stiffening of the 'hook' joint, which is known to control the 'flicking' observed in monotrichous bacteria - a type of instability in which the hook temporarily buckles to reorient the cell. Our analysis suggests that flicking relies on moments arising from 'wobbling' between the cell head and flagellum during swimming.

Hannah Laeverenz-Schlogelhofer, University of Exeter - Bioelectric control of ciliary dynamics in a walking single cell 

Unicellular eukaryotes are able to control and coordinate their motile appendages to achieve remarkably complex behaviours, such as animal-like hunting, predator-evasion, mating and feeding activities. To address the question of how single cells control behaviour, we study locomotor patterning in the unicellular eukaryote Euplotes, a single cell that walks and swims with 15 leg-like appendages called cirri (each a bundle of ~25-50 cilia). We combine high-speed imaging with simultaneous electrophysiological recordings to show how the cell’s membrane potential coordinates cirri movement, with distinct cirri behaving differently. A minimal mechanical model maps cirri dynamics to locomotor gait.

Isabella Guido, University of Surrey - Cytoskeletal active networks under external mechanical stimulation

Cytoskeletal networks such as microtubules and motor proteins drive vital cellular processes that, together with cargo delivery and cell division, also include providing mechanical stability when cells are exposed to external stresses. However, how the cytoskeleton orchestrates its components to respond to the environment is not yet clear. Here we show bioinspired systems resembling cytoskeletal networks and characterise their activity under the influence of external mechanical stimulation. We confine active networks of microtubules and kinesin motors in evaporating aqueous droplets. The flow field generated by Marangoni and capillary flow couples with the active stress of the microtubule-motor-protein network. We observe that this coupling influences the spatio-temporal distribution of the driving forces and the emergent behaviour of the system, which shows contraction and relaxation. By analysing such non-equilibrium systems, our study can contribute to understanding the response of biological structures to cues from external environment.

Anders Aufderhorst-Roberts, University of Durham - A Cell-Free Approach to Remodel and Mechanically Probe Intermediate Filament Networks

Cells are fundamental to all life, a role which demands mechanical versatility. Cells are soft, which enables them to divide but cells are also strong, which enables them to withstand stretching and shear. A major contributor to this versatility are the intermediate filaments (IFs) - cytoskeletal polymer-like proteins that can withstand large stresses and rapid deformations. I will describe IF networks can be probed in custom microfluidic chambers that allow network structural changes to be induced in situ. IF mechanics are probed through the video tracking of embedded passive probe particles. We show that homogeneous IF networks can be controllably assembled and demonstrate that their mechanics and structure can be adjusted through changes in ionic strength. I will also discuss how this approach may be useful for identifying the mechano-structural origins of other chemical processes in live cells.

Marcus Taylor, MPI for Infection Biology - The Super-molecular machines of the innate immune system: understanding how they work to building new ones

A feature of innate immune signalling is the self-assembly of helical protein filaments that activate downstream effectors. The critical biophysical properties of these helical assemblies required for signalling are not clearly defined. The Myddosome is an example of a helical oligomer composed of death domain (DD)-containing proteins MyD88 and members of the IRAK family. Myddosomes activate TRAF6 via repeating interacting motifs found in IRAKs. Here, we engineered a single-component signalosome composed of a chimeric MyD88. We further deconstructed this chimeric MyD88 and found the DD and helical assembly to be essential for signal transduction. We found a bacterial DD homolog, predicted to assemble in a helical filament, to be functionally interchangeable with the MyD88 DD. This work reveals that the de novo assembly of helical protein filaments is an ancient signalling mechanism and lays out a reductionist framework to dissect the required properties of signal transduction through these macromolecular assemblies.

 

P1

Becky Conners, University of Exeter - Filamentous phages 

Viruses are the most abundant biological entities on Earth; existing in many different shapes and sizes and affecting every ecosystem on our planet. Bacteriophages (or phages) are viruses that specifically infect bacteria. In addition to their impact on microbial life, phages are exploited as tools in molecular biology and biotechnology. The Ff (f1, fd or M13) phages represent a widely distributed group of filamentous viruses. Their genomes are protected from the environment by being packaged inside a protein capsid, forming a long, flexible filament of 1µm in length. We use cryo-electron microscopy techniques to determine the structure of these viruses and to investigate their mechanisms of infection, assembly, and egress from the host cell.

P2

Eli Cohen, Imperial College London - Co-evolution of cell shape, surface glycosylation and flagellar filament in C. jejuni. 

The human pathogen Campylobacter jejuni uses its bipolar flagella to drill through the thick gastric mucous in the host GI tract to reach favourable colonization sites. The selective pressure to be able to swim effectively in this high viscosity environment has resulted in a helical body shape, allowing the cell body to act as a drill, and a high-torque flagellar motor. Here, we will present additional adaptations to the flagellar filament and cell surface that allow C. jejuni to thrive in the host.

P3

Jade Sum, Imperial College London - Flagellar Fortitude: How does Campylobacter jejuni’s flagella confer flagellotropic phage resistance? 

As a major cause of gastroenteritis in the world, focus has shifted to Campylobacter jejuni and its interaction with bacteriophages to explore alternatives to antibiotic therapy, amidst the growing emergence of antibiotic-resistant bacteria. This review delves into the multifaceted roles of C. jejuni’s flagellins, FlaA and FlaB, highlighting their distinct functionalities and implications in defending against bacteriophages, particularly the flagellotropic bacteriophage CP220. Various investigations explored the different roles of these flagellins, showcasing FlaA’s involvement in motility and autoagglutination, juxtaposed with FlaB’s potential as a defense mechanism against flagellotropic bacteriophages. But despite these advancements, the precise mechanisms underlying FlaB’s resistance against bacteriophages remain elusive. It is imperative to examine in depth the process of flagellotropic phage attachment and infection, to unlock further insights into bacterial survival mechanisms and potential avenues for novel infection control strategies.

P4

Trishant Umrekar, Imperial College London - Altered mechanical properties in Campylobacter jejuni flagellins FlaA and FlaB demonstrate adaptations for motility  

Cellular motility across the three domains of life independently evolved molecular propellors composed of biological filaments. Motility in prokaryotic bacteria is facilitated by the flagellum, a molecular motor which turns a microns-long, proteinaceous, helical filament. Campylobacter jejuni, commonly found in the gastrointestinal tract of animals and a leading cause of human gastroenteritis, has co-evolved its flagellum and cell shape to corkscrew through viscous medium utilizing two polar filaments that wrap and trail the cell body. These filaments are composed of stretches of two near-identical flagellins. We use CryoEM to understand which residues cause mechanical differences between filaments of FlaA and FlaB. Our data yields near-atomic resolution maps of FlaA and FlaB. Molecular modelling reveals four key inter-subunit interactions causing stiffer FlaB filament segments. These differences in flexibility and superstructure facilitate wrapping (FlaA) and torque transmission (FlaB).

P5

Jan Cammann, Loughborough University - Active Spaghetti Collective Organization in Cyanobacteria 

Filamentous cyanobacteria can show fascinating examples of nonequilibrium self-organization, which, however, are not well understood from a physical perspective. We investigate the motility and collective organization of colonies of these simple multicellular lifeforms. As their area density increases, linear chains of cells gliding on a substrate show a transition from an isotropic distribution to bundles of filaments arranged in a reticulate pattern. Based on our experimental observations of individual behaviour and pairwise interactions, we introduce a nonreciprocal model accounting for the filaments large aspect ratio, fluctuations in curvature, motility, and nematic interactions. This minimal model of active filaments recapitulates the observations and rationalizes the appearance of a characteristic length scale in the system, based on the Péclet number of the cyanobacteria filaments. Reference: M. Faluweki, J. Cammann, et al. Phys. Rev. Lett. 131, 158303 (2023)

P6

Xiaomeng Ren, University of Bristol - Swimming by spinning: spinning-top type rotations regularize sperm swimming into persistently symmetric paths in 3D

Sperm modulate their flagellar symmetry to navigate through complex physico-chemical environments and achieve reproductive function. Yet it remains elusive how sperm swim forwards despite the inherent asymmetry of several components that constitutes the flagellar engine. Despite the critical importance of symmetry, or the lack of it, on sperm navigation and its physiological state, there is no methodology to date that can robustly detect the symmetry state of the beat in free-swimming sperm in 3D. How does symmetric progressive swimming emerge even for asymmetric beating, and how can beating (a)symmetry be inferred experimentally? Here, we numerically resolve the fluid mechanics of swimming around asymmetrically beating spermatozoa. This reveals that sperm spinning critically regularizes swimming into persistently symmetric paths in 3D, allowing sperm to swim forwards despite any imperfections on the beat. The sperm orientation in three-dimensions, and not the swimming path, can inform the symmetry state of the beat, eliminating the need of tracking the flagellum in 3D. We report a surprising correspondence between the movement of sperm and spinning-top experiments, indicating that the flagellum drives “spinning-top” type rotations during sperm swimming, and that this parallel is not a mere analogy. These results may prove essential in future studies on the role of (a)symmetry in spinning and swimming microorganisms and micro-robots, as body orientation detection has been vastly overlooked in favour of swimming path detection. Altogether, sperm rotation may provide a fool proof mechanism for forward propulsion and navigation in nature that would otherwise not be possible for flagella with broken symmetry.

P7

Samuel Bentley, University of Exeter - Flagella Beat and Motility Strategy in Microswimmers

Motility is a fundamental characteristic of life at all scales. At the microscale, free living cells often possess flagella for locomotion in the fluid environment. Microscopic algae show great variety in arrangements and coordination patterns of flagella, while displaying clear motile behaviours in response to stimuli e.g. photosynthetic algae navigating towards light sources (phototaxis). This project uses a range of techniques from population wide-assays to single-cell observation using micropipettes, across several microalgae species, to investigate motile responses to stimuli and understand motility strategy and behaviour.

P8

Finn Lobnow, MPI for Infection Biology Berlin, Germany - Bacterial Protein Domains can Restore Signaling in a Reductionist Signalosome

The formation of helical filaments is a recurring thresholding and amplification system in the innate immunity of metazoans. In particular, the architecture of signalosomes depends on the presence of protein domains with a six-helical bundle fold, present in all members of the so-called Death Domain Superfamily. The long-held belief that this superfamily evolved as part of the metazoan lineage was overturned when recent studies revealed the widespread presence of such protein domains in bacteria. AlphaFold-based protein complex predictions suggest a propensity of these domains to form higher-order assemblies. To investigate functional replaceability, we used a reductionist signalosome system in a eukaryotic cell line and exchanged the metazoan DD for various bacterial Death-Like Domains. The resulting signalosome assembly dynamics and signaling events were monitored using TIRF microscopy. Interestingly, several death-like domains from bacteria with “multicellular” life styles closely resemble assembly dynamics of metazoan DDs and rescued innate immune signaling in mammalian cells.

P9

Kelsey Cremin, University of Warwick - Formation of spatially organised structures driven by a filamentous cyanobacteria within a microbial community

Adapting a freshwater derived sample into lab conditions, we have recently developed a mid-complexity microbial community, dominated by a filamentous cyanobacteria that is named Fluctiforma Draycotensis. Combined with studies of the microscale motility mechanisms in this cyanobacterium, we are developing an across-magnitude understanding of spatially organised structures and associated function within this derived microbial community. In this work macro- and milli-scale imaging platforms are used to observe the formation of structures. We observe the cyanobacteria forming free-floating cyanobacteria granules, which encase a yellow material core found to be an iron-rich bacterial precipitate. Time-lapsed imaging reveals these granules form due to a foraging-like behaviour from the cyanobacteria, resulting in multiple iron precipitates being collected together and then enveloped by growing cyanobacteria. This granule formation creates an iron-rich, anoxic micro-environment that significantly differs from the greater culture environment. Herein, we take a community-wide view to explore both the production of the granule components and suggest possible species and community level consequences for such activities.

P10

Joseph Knight, University of Edinburgh - Probing the spatial networks of Labyrinthula zostera colonies

Labyrinthula zostera is a marine protist named after the seagrass species Zostera marina (or eelgrass) upon which it is resident and is believed to be pathogenic towards. Labyrinthula colonies are characterised through the secretion of an ectoplasmic net whose filament forms a connected network around which cells can move and drive colony expansion. In this poster, I outline a novel method for characterising these networks to gain spatiotemporal insight into colony growth through various network science metrics. Utilising a machine learning driven approach, we demonstrate a pipeline for processing timelapse microscopy data to show that Labyrinthula colonies form well defined spatial networks. This work hopes to further elucidate an understanding of Labyrinthula networks across a range of length scales, from the microscopic mechanisms of filament growth and alignment to the macroscale logic and organisation of the network as a whole.

P11

Alexander Boggon, University of Exeter - Emergent behavioural complexity in a ciliated microorganism

Many eukaryotic microorganisms display a range of motile behaviours characterised by the dynamic movement of cilia. We present a detailed biophysical characterisation of motility in the unicellular marine alga Pterosperma. We show the cell displays highly excitable behaviour collapsing into three distinct motility macrostates identified by stereotyped beating of its four cilia, exhibiting multiple discrete oscillatory modes. This includes a quiescent state of small amplitude, low frequency oscillations of unbundled cilia. Conversely, a bundled, synchronously beating ‘compound cilium’ allows swimming by propagating high amplitude waves with frequencies spanning an order of magnitude, and ultra-fast reorientations via large curvature bends. We map the dynamics of Pterosperma's behaviour across multiple spatio-temporal scales to reveal the behavioural complexity present. Low spatio-temporal resolution elucidates the population-wide context in which to understand the function of variable cilium beating, while high resolution allows tracking of ciliary waveforms and to resolve the dynamics of transitions between multistable modes. We complement this with sub-cellular imaging thereby providing the basis upon which to study the underlying physical principles that connect intracellular structures to ecologically relevant function.

P12

Luis Alberto Bezares Calderón, University of Exeter - Multiscale study of ciliary based flow sensation in zooplankton 

Ciliary structures are ideal structures to monitor changes in flow, as their bending is a function of the force exerted by the fluid. Such forces are transduced into a bioelectrical signal that leads to rapid or chronic changes in cell and organismal physiology. An integral understanding of the different steps in this process is still lacking. In this work, we introduce a system of motile sensory ciliated neurons in a planktonic animal larva that are exposed to the environment and activated by flow, but not by vibrations. Using calcium imaging we characterised the activation profile of these cells. With a combination of high temporal and spatial resolution microscopy, as well as molecular tools we are unravelling the mechanics of cilia deformation, the molecular players involved in the transduction cascade, and the underlying axonemal structures that may confer the sensitivity to flow. Behavioural assays and whole-body calcium imaging will help us determine how the larva uses the signals relayed cilia to control swimming in the face of flow-changing environments.

P13

Rebecca Poon, University of Exeter - Metachronal waves in the ciliary band of Platynereis dumerilii larvae 

Arrays of oscillating cilia often coordinate into a pattern known as a metachronal wave. Many theoretical and computational studies have shown that hydrodynamic coupling is sufficient to produce such waves. Various internal biological mechanisms are also hypothesized to affect the coordination of real ciliary arrays. However, relatively few experimental studies have characterised ciliary coordination in living organisms. We present a detailed study of the metachronal wave exhibited by the ciliary band of the larvae of a marine annelid, Platynereis dumerilii. Quantifying the wave reveals that it is far from uniform: instead, the underlying complexity of the cellular organisation results in discrete patterning of the frequency and wavelength. We then perturb the system by the addition of neurotransmitters, and by physically ‘interrupting’ the wave. Our results highlight complex features of ciliary metachronism not captured by simple hydrodynamic models.

P14

Tom Mason, Loughborough University - Active Particles immersed in nematics

Microswimmers exhibit fascinating behaviour due to the interplay of activity and hydrodynamics. In many natural environments, microswimmers have to navigate complex fluids containing elongated filament-like biopolymers, such as sperm in the reproductive tract. By means of nematic multi-particle collision dynamics simulations and analytical modelling, we find a rich dynamical behaviour of swimmers immersed in a nematic environment and confined within a channel. The confinement has drastic effects on the dynamics of the swimmers, and on their steady state. We find that pullers and neutral swimmers settle along the channel centerline, whereas pushers can hover in front of the walls, or display oscillatory dynamics depending on the strength of their propulsion and degree of confinement. These different dynamics depend on the competition between nematodynamic torque, wall-induced torque, and elastic forces. These interactions offer the opportunity for both control and transport in active nematic systems.

P15

Clément Moreau, CNRS Paris, France - Odd elastohydrodynamics: a novel description of active material and swimming patterns in a viscous fluid

Swimming in a fluid results in an interplay between elasticity, hydrodynamic interaction and internal activity. While the first two ingredients of this mix follow well-known physical principles, fundamental mechanical laws for its last component are yet to be fully understood. Recently, the concept of odd elasticity has been proposed to describe characteristic non-reciprocal interactions within active matter. Here, I will present our recently developed framework for micro-swimming dynamics based on an odd-elastic description of active interactions. After an introduction to odd elasticity and flagellar swimming modelling, I will go through the different building blocks of the odd-elastohydrodynamic theory, which notably relies on a canonical description of periodic swimming with a Hopf bifurcation and leads to defining ''odd elastic modulus'', measuring non-local and non-reciprocal interactions within the swimmer. I will discuss its physical interpretation and an application to experimental data on spermatozoon flagella. This work was conducted in collaboration with Prof. Kenta Ishimoto and Dr. Kento Yasuda.

P16

Rosie Cates, University of Cambridge - Instability of wall-bound filaments induced by molecular motors

Microtubule filaments found in biological cells may be anchored to the cell membrane at one end. Motor-driven transport of various organelles along these filaments generates flows of the cytoplasmic fluid (cytosol) inside the cell, which in turn produces motion and deformations of the filaments. By investigating the behaviour of the resulting fluid-structure problem, we reveal a novel instability of the filaments resulting in their alignment with the cell walls. We discuss different behaviours and investigate the effect of varying both the forcing and the wall anchoring condition. This instability mechanism may play a role in the generation of cell-spanning rotational fluid flows observed in Drosophila ooctyes.

P17

Lubna Danish, University of Exeter - Dynamics of Augmin and g-TuRC in Microtubule Branching 

Microtubules (MTs) are components of the cytoskeleton involved in the internal organization of eukaryote cells. They are highly dynamic polymers, composed of tubulin dimers, that grow and shrink depending on the presence of nucleating, stabilizing, or destabilizing proteins. The fine-tuned dynamics of MTs, as a population, are responsible for the formation of a bipolar mitotic spindle, capable of aligning and then segregating duplicated chromosomes during mitosis. Dynamic instability and polarity are two fundamental properties of the microtubules on which the proper functioning of mitosis depends. Research over the last years has identified the importance of two multisubunit protein complexes, known as g-TuRC and Augmin in the formation of microtubule branches from already existing MTs (microtubule branching) during cell division. It has been shown by our lab that in Drosophila, certain regions on Augmin subunits (Dgt3, Dgt5, and Dgt6) can directly bind to g-TuRC subunit dgp71WD and accumulate this MTs nucleator to the microtubule spindle. During my Ph.D research, I aim to comprehensively understand the structure of the g-TuRC using HDX-MS (Hydrogen-Deuterium Exchange Mass Spectrometry) and how its conformation changes when interacting with other proteins, particularly Augmin.

P18

Mike Deeks*, Jordan Hembrow, David Richards, University of Exeter - Reconfiguring actin networks in plant cells under microbial attack

The actin cytoskeleton of plant cells drives exocytosis, supports cytoarchitecture and is a dynamic high-speed distribution system for plant organelles. Invasion of plant cells by pathogenic microbes is met by rapid reconfiguration of the plant actin network.  Mutants and drug studies show that this is essential for preventing a breach of the plant cell by the microbe, but little is understood about how these rearrangements are achieved. We have identified a protein component required to consolidate these changes, but we have also confirmed that the responses can occur in seconds by another mechanism that remains elusive. In collaboration with David Richards (LSI) we have developed a means to measure and compare network metrics to improve phenotyping during hypothesis testing and are currently exploring means to compare localised network characteristics.

P19

Chisato Tsuji, University of Bristol - Composition of microtubule lumenal actin

Crosstalk between the actin and microtubule cytoskeletons is essential for many cellular processes. Recent studies have shown that microtubules and F-actin can assemble to form a composite structure where F-actin occupies the microtubule lumen. Whether these cytoskeletal hybrids exist in physiological settings and how they are formed is unclear. We show that the short-crossover Class I actin filament previously identified inside microtubules in human HAP1 cells is cofilin-bound F-actin. Lumenal F-actin can be reconstituted in vitro, but cofilin is not essential. Moreover, actin filaments with both cofilin-bound and canonical morphologies reside within platelet microtubules under physiological conditions. We propose that stress placed upon the microtubule network during motor-driven microtubule looping and sliding may facilitate the incorporation of actin into microtubules.

 

 

By train

Exeter has two railway stations - Exeter St David's (main station) and Exeter Central. Exeter St David's Station is approximately 10 minutes walk from the Streatham Campus and taxis are available. The average journey time from London Paddington is 2 hours 30 minutes to Exeter. See Streatham Campus map for the walking route.

Use National Rail Enquiries to plan your route. For passenger information phone 08457 484950.

By plane

Direct flights operate into Exeter Airport and some airports in the United Kingdom.

Taxis from the airport can be pre-booked from Apple Central Taxis, previously Gemini Taxis. The journey takes approx 1.5 hrs.

Alternatively you can fly to Bristol Airport. Taxis from the airport can be pre-booked from Apple Central Taxis (see above) or you can use the train service to Exeter St David’s via Bristol Temple Meads. See the National Rail website for details.

Another option is to fly to London Heathrow Airport. Use the Heathrow Express to London Paddington and then take a train from there to Exeter St David’s (this will be the Great Western Railway Service to Exeter, Paignton, Plymouth or Penzance). See the National Rail website for details.

Hotels

There are a number of hotels in town (about 15-20 minute walk from the university), participants should book early to avoid disappointment. Some suggested hotels (including approximate prices) are shown below. There are also a number of B&Bs in the area (Queens court, the Clock Tower, Raffles Hotel etc).

  • Premier Inn Exeter Central – £61 per night
    (0.7 miles to conference venue, 0.6 miles from city centre,)
  • Mercure Exeter Rougemont – £102 per night
    (1 mile to Conference Centre, 0.2miles to City Centre, right opposite Exeter Central Station,)
  • Leonardo Hotel Exeter – £120 per night
    (1.1 miles to Conference Venue, 0.5 miles to City Centre)
  • Hotel Indigo – £102 per night
    (1.2 miles to Conference Centre, 0.1 miles to city centre,)
  • Mercure Exeter Southgate Hotel – £213 per night
    (1.4 miles to Conference Venue, 0.2 miles to City Centre,)
  • Holiday Inn Express Exeter City Centre – £78 per night
    (1.5 miles to Conference Centre, 0.3 miles to city centre)
  • Hotel du Vin Exeter – £104 per night
    (1.5 miles to conference venue, 0.3 miles from city centre)

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Thank you to PoLNet3 and the LSI for their financial support.