Times are shown in Japan time (JST). 


Monday 6 Tuesday 7 Wednesday 8

Thursday 9

9:40   Sawai Nourmohammad Fakhri
10:20   Shen Furusawa Kawaguchi
17:00   Rodenfels Mitarai Sartori
17:40   Ritort Bhat Kusumi
20:10 Introduction      
20:20 Esposito Tlusty Roldan (Canceled) Tang
21:00 Horowitz Murugan Sivak Sagawa


Monday 6

Massimiliano Esposito (U. Luxembourg)

"Energy and information transduction from synthetic molecular motors to metabolism"

"The complexity of cellular biology has its root in chemistry. I will briefly summarize the state of the art in the nonequilibrium thermodynamics of open chemical reaction networks (CRNs) and show how it can be used to study energy and information transduction from simple synthetic molecular motors to complex CRNs such as metabolism.

Jordan Horowitz (U. Michigan)

"Nonequilibrium limits to biochemical sensitivity"

Living things must be very sensitive to small chemical changes to accomplish key functions, such as sensing or DNA replication. While at thermodynamic equilibrium there are well-known sensitivity limits, many biochemical functions are carried out away from equilibrium opening the possibility for drastic enhancements. This raises fundamental questions about the trade-offs between nonequilibrium driving and a system’s sensitivity to external changes. Inspired by this question, I will introduce in this talk a decomposition of nonequilibrium response into three physically-motivated families of perturbations. For each family, I will discuss an equality or inequality valid arbitrarily far from equilibrium that links the system’s sensitivity to the strength of nonequilibrium driving. I will then discuss how these predictions rationalize known energetic requirements for some common biochemical motifs and provide new limits to others.

Tuesday 7

Satoshi Sawai (U. Tokyo)

"Tissue patterning dynamics in social amoebae and its relation to heterogeneity in the cellular metabolism"

Cell-cell heterogeneity in growth and metabolism is at the basis of understanding the origin of symmetry breaking and how tissue-level heterogeneity arises during multicellular development. The social amoeba Dictyostelium is known for its unique life-cycle that switches from the solitary growth phase to multicellular development under nutrient scarcity. A large body of work in this system points to strong correlation between the cell-cycle position/length during the solitary growth stage and the eventual cell-type fate determination, however how it relates to the metabolism and the survival of single-cells is still largely unexplored. In this talk, I will present our ongoing works that address the self-organizing nature of the tissue forming dynamics and its relation to metabolic heterogeneity early in the solitary growth stage.

Amy Shen (OIST)

"Population genetics of bacteria in microchannels"

Many microbial populations proliferate in small channels. In such environments, reproducing cells organize in parallel lanes. Reproducing cells shift these lanes, potentially expelling other cells from the channel. In this work, we combine theory and experiments to understand how this dynamics affects the diversity of a microbial population. We theoretically predict that genetic diversity is quickly lost along lanes of cells. Our experiments confirm that a population of proliferating E. coli in a microchannel organizes into lanes of genetically identical cells within a few generations. Our findings elucidate the effect of lane formation on populations evolution, with potential applications ranging from microbial ecology in soil to dynamics of epithelial tissues in higher organisms.

Jonathan Rodenfels (MPI-CBG)

"The energetic costs of embryonic development"

Living biological systems are metabolically active, open systems that constantly exchange matter and energy with their environment. They function out of thermodynamic equilibrium and continuously use metabolic pathways to obtain energy from chemical bonds derived from nutrients to fulfill the system's energetic requirements. To understand how cells and organisms function, we need to determine how metabolic energy is partitioned among the complex array of cellular processes that are necessary for life at any scale, from isolated biochemical networks to quiescent and highly proliferative cells to organismal growth and development. To investigate the energetics of embryonic development, we use calorimetry to quantitatively measure the flow of energy in form of heat between developing embryos of phylogenetically distant species and their surroundings. During early cleavage stage development, the heat dissipation rate increased over time and with cell number. Unexpectedly, we found that the heat dissipation rate oscillated with periods matching the synchronous early embryonic cell cycle. By combining these measurements with specific perturbations, energetic cost estimates, and modeling, we will show that the energetic costs associated with a given biological process during early development can be estimated, and thus, provides a means towards understanding the energetics of biological systems.

Felix Ritort (U. Barcelona)

"Dissipation reduction in nonequilibrium systems with feedback: from
protocols to strategies"

Single-molecule experiments permit us to experimentally test fundamental
results in the thermodynamics of information in the nanoscale [1]. Recently, we introduced a continuous Maxwell demon for information-to-energy conversion in equilibrium systems and applied it for a DNA hairpin pulled with optical tweezers [2]. In this talk I present a new application of information-to-energy conversion in nonequilibrium systems, aimed to reduce dissipation and improve free energy
determination in DNA pulling experiments (information-to-measurement efficiency)[3,4]. We introduce feedback strategies as a correlated sequence of feedback protocols and show how they markedly reduce dissipation enhancing information-tomeasurement efficiency. Our study underlines the role of temporal correlations in feedback strategies for efficient information-to-energy conversion in small systems [5].

1. F. Ritort, The noisy and marvelous molecular world of biology, Inventions, 4(2)
(2019) 24

2. M. Ribezzi-Crivellari and F. Ritort, Large work extraction and the Landauer limit in
Continuous Maxwell Demon, Nature Physics 15 (2019) 660–664
3. M. Rico-Pasto, R. K. Schmitt, M. Ribezzi-Crivellari, J. M. Parrondo, H. Linke, J.
Johansson and F. Ritort,
Dissipation reduction and information-to-measurement
conversion in DNA pulling experiments with feedback,
Physical Review
11 (2021) 031052
4. R. K. Schmitt, P. P. Potts, H. Linke, M. Rico-Pasto, J. Johansson and F. Ritort, P.
Information-to-work conversion in single molecule experiments: from
discrete to continuous feedback,, submitted
5. J. P. Garrahan and F. Ritort,
Generalized Continuous Maxwell Demons,, submitted

Tsvi Tlusty (IBS, Ulsan)

"A general theory of specific binding: insights from a genetic, mechano-chemical protein model"

Proteins need to selectively interact with specific targets among a multitude of similar molecules in the cell. Despite a firm physical understanding of binding interactions, we lack a general theory of how proteins evolve high specificity. We will discuss a model that combines chemistry, mechanics, and genetics and explains how their interplay governs the evolution of specific protein-ligand interactions. The model shows that harder discrimination tasks require more collective and precise coaction of structure, forces, and movements. Proteins can achieve this through correlated mutations extending far from a binding site, which finetune the localized interaction with the ligand. Thus, the solution to more complicated tasks is aided by increasing the protein, and proteins become more evolvable and robust when they are larger than the bare minimum required for discrimination. Altogether, the model proposes a possible answer to the natural question “why are proteins so big?'': molecular discrimination is often a hard task best performed by adding more layers to the protein.

Arvind Murugan (U. Chicago)

"The evolution of proofreading"


Wednesday 8

Armita Nourmohammad (U. Washington)

"Organization and encoding of memory in evolving environments"

Biological systems, ranging from the brain to the immune system, store memory of molecular interactions to efficiently recognize and respond to stimuli. However, the strategies to encode memory can vary largely across different systems. In this talk, I will discuss how statistics and dynamics of stimuli should determine the optimal memory encoding strategies in biological networks. In particular, I will contrast the compartmentalized memory in the adaptive immune system, which primarily interacts with evolving pathogens, with the distributed memory in the olfactory cortex, which interacts with relatively static odor molecules. Focusing on the adaptive immune system, I will discuss how memory encoding could be understood in light of host-pathogen coevolution. Specifically, I will show that to achieve a long-term benefit for the host, immune memory should be actively regulated, with a preference for cross-reactive receptors with a moderate affinity against pathogens as opposed to high affinity receptors. Our theory also predicts that an organism’s life-expectancy should strongly impact the cross-reactivity of its immune memory, and we expect organisms with shorter life expectancy to carry more cross-reactive memory. This theoretical prediction can guide more comprehensive cross-species comparisons of immune systems, which is currently missing from immunological studies.

Chikara Furusawa (U. Tokyo, RIKEN)

"Toward prediction and control of microbial evolution: Analysis of phenotypic constraints in laboratory evolution"

Biological systems change their state in order to adapt and evolve to changing environmental conditions. However, despite the recognition of the importance of clarifying the adaptive and evolutionary capabilities of organisms, research on the evolvability and plasticity of organisms remains at a qualitative level. To clarify how evolutionary processes are constrained in high-dimensional phenotypic and genotypic space, we performed laboratory evolution under various (>100) stress environments and analyzed phenotypic and genomic sequence changes [1,2]. These comprehensive analyses revealed that changes in expression are restricted to low-dimensional dynamics, while diverse genomic changes contribute to similar phenotypic changes. To further analyze the nature of the evolutionary constraints, we performed computer simulations of adaptive evolution using a simple cellular model. Again, we found that changes in cell state in adaptation and evolution are generally restricted to low-dimensional dynamics [3]. Based on these results, we would like to discuss the nature of phenotypic plasticity and constraints in bacterial evolution and possible strategies to predict and control evolutionary dynamics.
[1] S. Suzuki, T. Horinouchi, and C. Furusawa, Nature Comm., 5:5792 (2014)
[2] T. Maeda et al, Nature Comm., 11:5970 (2020)
[3] C. Furusawa and K. Kaneko, Phys. Rev. E, 97(4-1):042410 (2018)

Namiko Mitarai (U. Copenhagen)

"Protection of bacteriophage-sensitive Escherichia coli by lysogens: importance of virus adsorption process"

Some viruses that infect bacteria, temperate bacteriophages, can confer immunity to infection by the same virus. Here we report λ-immune bacteria could protect λ-sensitive bacteria from killing by phage λ in mixed culture. The protection depended on the extent to which the immune bacteria were able to adsorb the phage. Reconciling modeling with experiment led to identifying a decline in protection as bacteria stopped growing. Adsorption of λ was compromised by inhibition of bacterial energy metabolism, explaining the loss of protection as bacterial growth ceased.

Deepak Bhat (OIST)

"Speed variations of bacterial replisomes"

Replisomes are multi-protein complexes that replicate genomes with remarkable speed and accuracy. In bacteria, two replisomes initiate replication at a well-defined origin site on the circular genome, progress in opposite directions, and complete replication upon encountering each other in a terminal region. Precise features of replisome dynamics, such as whether their speed is approximately constant or varies along the genome, are important to determine the location of their encounter point and the distribution of replication errors on the genome. But this detailed information is hard to obtain. We developed a mathematical model to infer the replisome dynamics from the DNA abundance in a growing bacterial population. I will discuss our findings in detail in this talk.

Edgar Roldan (ICTP)

"Modelling Active Non-Markovian Oscillations in the ear of the Bullfrog"

Modelling noisy oscillations of active systems is one of the current challenges in physics and biology. Because the physical mechanisms of such processes are often difficult to identify, we propose a linear stochastic model driven by a non-Markovian bistable noise that is capable of generating self-sustained periodic oscillation. We derive analytical predictions for most relevant dynamical and thermodynamic properties of the model. This minimal model turns out to describe accurately bistable-like oscillatory motion of hair bundles in bullfrog sacculus, extracted from experimental data. Based on and in agreement with these data, we estimate the power required to sustain such active oscillations to be of the order of one hundred kBT per oscillation cycle.

[1] G. Tucci, et al.,  arXiv:2201.12171 (2022)

David Sivak (U. Simon Fraser)

"Information thermodynamics of the transition-path ensemble"

The reaction coordinate describing a transition between reactant and product is a fundamental concept in the theory of chemical reactions. Within transition-path theory, a quantitative definition of the reaction coordinate is found in the committor, which is the probability that a trajectory initiated from a given microstate first reaches the product before the reactant. Here we develop an information-theoretic origin for the committor and show how selecting transition paths from a long ergodic equilibrium trajectory induces entropy production which exactly equals the information that system dynamics provide about the reactivity of trajectories. This equality of entropy production and dynamical information generation also holds at the level of arbitrary individual coordinates, providing parallel measures of the coordinate's relevance to the reaction, each of which is maximized by the committor.

Thursday 9

Nikta Fakhri (MIT)

"Odd dynamics of living chiral crystals"


Kyogo Kawaguchi (RIKEN)

"Probing the rules of interaction in biological agents"

An outstanding theme of biophysics is to understand the rules of the collective dynamics at multiple scales, ranging from multicellular tissues to biomolecules. For the tissue level dynamics, we have been studying how cultured neural progenitor cells (NPCs), which undergo self-propelled motion with liquid-crystal-like cell-to-cell interactions, can exhibit large structures with handedness by controlling the initial seeding condition. This chirality also leads to a robust unidirectional cell flow localized near the boundary of the culture substrates. Here we will describe our recent results on estimating the interactions between the cells that consistently explain such macroscopic behavior. For the molecular level phenomena, we have been interested in finding the rules of condensation in heteropolymers such as protein molecules and chromatin. We will introduce a data-driven approach to probe these rules by building a subcellular localization estimator of intrinsically disordered regions in proteins.

Pablo Sartori (Gulbenkian Institute)

"Evolutionary conservation of structural mechanics in ATP synthase"

The function of proteins and their assemblies is determined by changes in their atomic structure. However, despite tremendous experimental and computational advances on determining protein structures, analysis of such structures relies on visual inspection and rudimentary quantitative methods.

I will present a method to quantify structural changes of protein assemblies based on non-linear mechanics. This method provides two types of local information: alignment-dependent properties, e.g. rotation angles; and alignment-independent properties, e.g.principal stretches. Applying this method to the ATP synthase reveals, despite prevalent asymmetries, strong conservation of mehanically strained residues on chains that perform the same function. Furthermore, comparing mechanical strain among ATP synthases of different species reveals that functional conservation across different species dominates over conservation within species.

Our general method therefore provides a quantitative approach to quantify structural deformations, and is capable of identifying stable patterns across the tree of life.


Akihiro Kusumi (OIST)

"Metastable signal integration platform as revealed by single-molecule imaging"

Using single-molecule imaging, we found a nanometer-scale (50-80 nm) liquid-like protein assembly on the PM cytoplasmic surface (at a density of ~2-µm apart from each other on average, with a lifetime of ~10 s), working as the signal transduction and integration platform for receptors, including GPI-anchored receptors (GPI-ARs), receptor-type tyrosine kinases (RTKs), and GPCRs. The platform consists of integrin, talin, RIAM, VASP, and zyxin, and is thus termed iTRVZ. These molecules are known as focal-adhesion constituents, but iTRVZ is distinct from focal adhesions, because iTRVZ exists on both the apical and basal PMs and lack vinculin. The iTRVZ formation is driven by specific protein-protein interactions, liquid-liquid phase separation, and interactions with the actin filaments and raft domains via PI(4,5)P2. iTRVZ integrates and amplifies the GPI-AR and RTK signals in a strongly non-linear fashion, and thus works as the AND gate (coincidence detector) and noise filter. These findings greatly advance our understanding of the mechanism for crosstalk between signalling pathways.

Evelyn Tang (U. Rice)

"Protected edge currents in stochastic and cellular systems"

Cells exhibit various emergent dynamics necessary for system regulation, growth, and motility. However, how robust dynamics arises from the stochastic components remains unclear. Towards understanding this, we develop topological theories that support robust edge states, effectively reducing the system dynamics to a lower-dimensional subspace that is qualitatively different from stability within parameter space. In particular, we will introduce stochastic networks in molecular configuration space that enable different phenomena from a global clock, stochastic growth and shrinkage, to synchronization. These nonequilibrium systems further possess uniquely non-Hermitian features with new implications for system energetics. More broadly, our work provides a blueprint for the design and control of novel and robust function in living and active systems.

Takahiro Sagawa (U. Tokyo) 

"Non-Hermitian and Nonlinear Topology of Active Matter"

Topological materials have attracted much interest not only in condensed matter physics but also in various fields including active matter. An important concept is the principle called the bulk-boundary correspondence, which guarantees the one-to-one correspondence between nonzero bulk topological invariants and gapless boundary-localized modes. Unlike conventional condensed matter, dynamics of active matter is relevant to non-Hermitian or nonlinear physics. In this talk, we focus on unconventional topological aspects of active matter and discuss unique topological phenomena. First, we find that one can protect boundary modes in an unconventional manner by utilizing exceptional points, gapless structures unique to non-Hermitian systems, leading to the breakdown of the bulk-boundary correspondence [1]. Second, we extend the notion of topology to nonlinear oscillators and demonstrate a phenomenon named topological synchronization, where the edge oscillators are synchronized while the bulk ones are chaotic [2].
[1] K. Sone, Y. Ashida, and T. Sagawa, Nat. Commun. 11, 5745 (2020).
[2] K. Sone, Y. Ashida, and T. Sagawa, arXiv:2012.09479 (2020).