Measurement of natural systems typically involves perturbation and interpretation. In this talk, I will discuss the implications of measurement in the context of RNA in gene expression in human cells. I will focus on measurements of RNA biology using high-throughput sequencing, which are powerful for their scale but also involve perturbations…

The adaptive immune system is able to learn from changing experiences to better fit an unforeseen future, thanks to a large and diverse collective of cells expressing unique antigen receptors and capable of rapid Darwinian evolution. However, naturally occurring immune responses exhibit limits in efficacy, speed and capacity to adapt to novel…

My lab studies the brains of larval fruit flies as models of neural computation. We are interested in the rules by which the larval brain transforms sensory input into motor output to navigate an uncertain environment, how the larva’s brain changes these rules as it learns new information, and how these rules and changes are encoded in the…

How does learning occur? Neural networks learn via optimization, where a loss function is minimized by a computer to achieve the desired result. But physical networks such as mechanical spring networks or flow networks have no central processor so they cannot minimize such a loss function. An alternative is to encode local rules into those…

The new field of stochastic thermodynamics allows us to analyze the thermodynamic behavior of dynamic systems arbitrarily far from thermal equilibrium, and has produced many powerful theorems concerning phenomena completely absent in traditional statistical physics. However, to date stochastic thermodynamics has (mostly) been applied to systems…

Mechanical stability and shape changes of cells are determined by the dynamic interplay of four distinct cytoskeletal networks, made of actin filaments, microtubules, intermediate filaments and septins. These four filamentous systems contribute different structural and dynamical properties, enabling specific cellular…

Liquid-liquid phase separation of cell membranes exemplifies a biological system leveraging a physical concept to achieve a chemical end. Here, we show that yeast actively tune the transition temperature of their vacuole membranes to be close to the yeast's growth temperature, which implies that the membrane's proximity to the miscibility…

Understanding the physics of living systems allows us to design new materials that are active and adaptive, akin to cells and tissues. Conversely, these active matter systems can reveal fundamental principles in physics and biology. In this talk, I will discuss three systems that feature this synergy, ranging from the molecular to the…

To understand computation in the brain, one needs to understand the input-output relationships for neural circuits and the anatomical and functional properties of individual neurons therein. Optical microscopy has emerged as an ideal tool in this quest, as it is capable of recording the activity of neurons distributed over millimeter dimensions…

After a century of biochemical and genetic onslaught on the embryo we are left with an inexhaustive parts list with an increasingly baroque logic. How do we begin to assemble complex living systems from knowledge of the parts list? In this talk I will attempt to pursue a statistical (physics) approach to discerning the design principles that…

Controlling interfacial structure and dynamics of phase separating fluid mixtures is key to creating diverse functional materials. Traditionally, this is accomplished by controlling interface chemistry, through the presence of surface-modifying amphiphilic agents. Using a phase separating mixture of active and passive fluids, we study how…

The most celebrated corners of machine learning over the past decades are those successful at predicting - e.g., spam classification, medical diagnoses, or cat faces. But machine learning as actually used in practice is commonly prescriptive rather than predictive: decisions must be made in order to maximize a reward. The…

Many innate behaviors are the result of multiple sensorimotor programs that are dynamically coordinated to produce higher-order behaviors such as courtship or architecture. Extended phenotypes such as architecture are especially useful for ethological study because the structure itself is a physical record of behavioral intent. A particularly…

Natural ecological communities display striking features, such as high biodiversity and a wide range of dynamics, that have been difficult to explain in a unified framework. Using experimental bacterial microcosms, we have performed the first direct test of recent theory predicting that simple aggregate parameters…

Photosynthesis presents a paradox of solar energy: the maximum quantum efficiency of photosystem II likely surpasses that of any engineered system, but in environments with high solar flux, photosynthetic organisms are famously wasteful and resource inefficient. For example, even in agricultural systems bred for maximum resource efficiency such…

Membrane curvature is required for many cellular processes, from assembly of highly curved trafficking vesicles to extension of needle-like filopodia. Consequently, defects in membrane curvature play a role in most human diseases, including altered recycling of receptors in cancer and diabetes, targeting of filopodia by pathogens, and hijacking…

We have recently discovered that there are biological proteins that phase separate out of solution to form protein-dense droplets. These so-called protein condensates have been identified in an extremely large range of important biological processes. Increasingly, we find that the exact material nature of the liquid-like condensates (such as…

Pattern formation is ubiquitous in biological systems. While pattern formations are often associated with Turing-like reaction-diffusion systems, biology also exploits many other mechanisms such as mechanical instabilities and phase separation. In this talk, I will discuss how mechanical instabilities cause the wrinkling of bacterial biofilms…

Gene expression in all organisms is controlled by short DNA and RNA sequences called cis-regulatory elements (CREs). Proteins in the cellular milieu bind to nucleic acid sequences present within CREs, interact with one another, and thus form macromolecular complexes that modulate the expression of nearby genes. My lab uses…

The rod-shaped bacterium Escherichia coli proliferates by a process of elongation, followed by constriction at its centre to create new cell poles. Despite intense study, some apparently simple questions about the dynamics of growth and division in E. coli continue to be debated - these include whether the cell length increases exponentially or…

Active materials such as bacteria, molecular motors and eukaryotic cells continuously transform chemical energy taken from their surroundings to mechanical work. Dense active matter shows mesoscale turbulence, the emergence of chaotic flow structures characterised by high vorticity and self-propelled topological defects. I shall describe the…

Living systems need to remember information about their environment in order to take decisions that ultimately ensure survival. But storing information about past experiences costs energy, while only a fraction of the vast amount of information available can be useful to the living system. An intelligent memory formation strategy should take…

Active processes in living systems create a novel class of non-equilibrium material composed of many interacting parts that individually consume energy and collectively generate motion or mechanical stress. In this talk, I will discuss experimental tools and conceptual frameworks we develop to uncover laws governing order, phase transitions and…

Perception, attention and working memory are fundamental cognitive functions, which are based on parallel processing in many brain areas. Neuronal oscillations at sub-second timescales and their phase correlations a.k.a. phase-synchronization are putative mechanisms for the coordination of neuronal processing and…

One of the characteristic features of many marine dinoflagellates is their bioluminescence, which lights up nighttime breaking waves or seawater sliced
by a ship’s prow. While the internal biochemistry of light production by these microorganisms is well established, the manner by which fluid shear or mechanical
forces trigger…

Morphogenesis, the emergence of functional form in a developing organism, is one of the most remarkable examples of pattern formation in nature. Despite substantial progress, we still do not understand the organizational principles underlying the convergence of this process, across scales, to form viable organisms under variable conditions. We…

Simple organisms manage to thrive in complex environments. Remembering information about the environment is key to take decisions. Physarum polycephalum excels as a giant unicellular eukaryote being even able to solve optimisation problems despite the lack of a nervous system. Here, we follow experimentally the organism's response to a nutrient…

An animal eye is only as efficient as the organism’s behavioral constraints demand it to be. Efficient coding has been a successful organizational principle in vision, and to make a more general theory, behavioral, mechanistic, and even evolutionary constraints need to be added to this framework. In our work, we use a mix of known computational…

Many mature bacterial colonies and biofilms are complex three-dimensional (3D) structures. A key step in their developmental program is a transition from a two-dimensional (2D) monolayer into a 3D architecture. Despite the importance of controlling the growth of microbial colonies and biofilms in a variety of medical and industrial settings,…

The metabolic function of microbial communities emerges through a complex hierarchy of genome-encoded processes, from gene expression to interactions between diverse taxa. Therefore, a central challenge for microbial ecology is deciphering how genomic structure determines metabolic function in communities. Here we show, for the process of…

Cells across the tree of life respond to a sudden, nonlethal rise in temperature--heat shock--in similar ways. Following heat shock, proteins and mRNAs form clumps, certain genes turn on, and protein synthesis and cell growth sharply decline. The standard interpretation of these long-studied phenomena has held that thermal energy causes…

When experimenting with a large pool of species, a common problem is to determine a priori whether a certain subset of species can coexist when co-cultured. We propose a simple statistical model in which a number of species assemblages are observed, and the coexistence of novel assemblages is predicted out-of-fit. We…

We have been working to measure and understand how ion fluxes and ionic interactions regulate fundamental biological processes, and in particular promote stress tolerance in bacteria. I will present our recent work that builds on our discovery of action potentials generated within bacterial biofilms. Specifically, we showed…

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We review the dynamics of acute immunizing infections. We then use this as a backdrop to discuss the dynamics and control of the ongoing Coronavirus pandemic.

The study of small experimental communities has been key to the development of ecology as a discipline. Yet, for most ecological communities, the number of experiments required to build, model, or analyze the system vastly exceeds what is feasible, rendering these communities experimentally intractable. To address this challenge, we present a…

To understand computation in the brain, one needs to understand the input-output relationships for neural circuits and the anatomical and functional relationships of individual neurons therein. Optical microscopy has emerged as an ideal tool in this quest, as it is capable of recording the activity of neurons distributed over millimeter…

Cells across the tree of life respond to a sudden, nonlethal rise in temperature--heat shock--in similar ways. Following heat shock, proteins and mRNAs form clumps, certain genes turn on, and protein synthesis and cell growth sharply decline. The standard interpretation of these long-studied phenomena has held that thermal energy causes…

Our lab develops new imaging approaches for visualizing bacterial physiology in relevant contexts: We use live-cell single-molecule localization microscopy and lattice-light sheet microscopy to access 3D spatial and temporal information with high resolution. At molecular and cellular length scales, our research focuses on understanding how Gram…

Spinning disk confocal modules are “core facility friendly”; they insert conveniently between a commercial microscope base and camera, improve image quality and add no significant drawbacks. In contrast, high numerical aperture (NA) light sheet microscopy often requires radical sample modification, substantial user re-training and fully…

While efficient coding has been a successful organizational principle in visual neuroscience, to make a more general theory behavioral, mechanistic, and even evolutionary constraints need to be added to this framework. In our work, we use a mix of known computational goals and detailed behavioral measurements to add constraints to the notion of…

The immune responses that defend us against pathogens are driven by stochastic processes amongst populations of cells. Enormous progress in immunology over the last few decades has identified most of the components of this complex system, including the cell types and the molecules used for communication. But understanding how the dynamics of…

Bacteria exhibit a high degree of intracellular macromolecular crowding. To control the level of crowding cells must increase their volumes in response to the accumulation of biomass during growth. This coordination is fundamentally not understood in any cell type. Using rod-shaped bacteria Escherichia coli and Bacillus subtilis

Two of the most fundamental questions of sensory neuroscience are: 1) how is stimulus information represented by neuronal activity? and 2) what features of this activity are read out to guide behavior? The first question has been the subject of a large body of work across different sensory modalities. The second question remains a significant…

Macromolecular protein complexes perform essential biological functions across life forms. The assembly of such complexes is known to be regulated at the level of gene transcription, but little is known about the factors that control their assembly once the mature protein subunits enter their target space (cytoplasm, membrane, or cell wall)…

Organisms are an evolutionary masterpiece of feedback control, featuring a mind-boggling capacity to self-correct. In this talk, we discuss our attempts to both understand feedback control in cells and to forward engineer it with de novo designed proteins.

Visual systems detect many features of natural scenes, including motion. Motion detection guides critical behaviors like hunting, evading predators, and finding mates. It can be framed as an inference problem, in which light intensity measurements are combined to estimate a latent variable of image velocity. Interestingly, several patterns of…

Nucleosomes help structure chromosomes by compacting DNA into fibers.  Chromatin organization plays an important role for regulating gene expression; however, due to the highly crowded nuclear environment and the nanometer length scales of chromatin fibers, it has been very difficult to visualize chromatin in vivo. We have overcome this…

Microtubules are active biological polymers known to stochastically switch between phases of growth and shrinkage, a behavior termed ‘dynamic instability’. Microtubule treadmilling, in which the microtubule plus end grows while the minus end shrinks, is also observed in cells. While dynamic instability has been widely studied in vitro,…

I will describe a new approach that we are currently developing to describe developmental dynamics. We are using simple machine learning techniques to project the dynamics of the Drosophila gap genes onto a low dimensional space, allowing us to build "geometric" models. We uncover a relatively simple dynamics in latent space, where we identify…

In sperm, DNA is tightly compacted to create a small, hydrodynamic sperm head. This dramatic reorganization of the nucleus is carried out by protamine proteins that fold the DNA into loops and toroids. Here, I'll talk about the pathway and physical mechanism of that DNA folding.  We will look at images of single molecules of DNA with bound…

The immune repertoire responds to a wide variety of pathogenic threats. Immune repertoire sequencing experiments give us insight into the composition of these repertoires. Since the functioning of the repertoire relies on statistical properties, statistical analysis is needed to identify responding clones. Using such methods I will describe the…

 I will discuss studies of the mechanics and structure of metaphase chromosomes and nuclei extracted from mammalian cells using glass micropipettes. Using a combination of mechanical, biochemical and genetic approaches we have shown that the metaphase chromosome is a "chromatin gel", without a contiguous protein scaffold, and via SMC2 siRNA…

The physical limits to chemical sensing have been established and tested for single cells. However, recent experiments have demonstrated that cells can surpass these limits when they communicate. The theoretical limits to the precision of collective sensing are still poorly understood. In this talk, I will discuss three types of cell-cell…

JCVI-syn3A, a robust minimal cell with a 543 kbp genome and 493 genes, provides a versatile platform to study the principles of life (Breuer et al. eLife 2019). Using the vast amount of experimental information available on its precursor, Mycoplasma mycoides capri, we assembled a near-complete essential metabolic network with 98% of enzymatic…

Collective migration of cohesive groups of cells is a hallmark of the tissue remodeling events that underlie embryonic morphogenesis, wound repair and cancer invasion. In this collective migration, supra-cellular properties such as collective polarization or force generation emerge and eventually control large- scale tissue organization. This…

In physics and engineering dimensionless numbers frequently help to characterize the state of a system. I will present a series of vignettes about unusually large dimensionless numbers that arise in brain science. These can indicate issues that are poorly understood, and in some cases clearly misunderstood.

Early embryogenesis of most metazoans is characterized by rapid and synchronous cleavage divisions. After fertilization, Drosophila embryos undergo 13 swift rounds of DNA replication and mitosis without cytokinesis, resulting in a multinucleated syncytium containing about 6,000 nuclei. The very first cycles involve substantial flows, both in…

Optical reporters of neural activity have improved dramatically over the past decade. Recent developments in optical imaging approaches have unlocked the power of these indicators and can now provide real-time read-outs from large populations of brain cells in a wide range of living organisms. We have recently contributed two imaging methods to…

The human adaptive immune system makes robust decisions which regulate quantitative and qualitative parameters of a complex physiological system, to prevent invasion and destruction of tissues by the enormous array of microorganisms which share our environment. Remarkably, these decisions are made by a…

In vivo, the human genome folds into a characteristic ensemble of 3D structures. The mechanism driving the folding process remains unknown. A theoretical model for chromatin (minimal chromatin model) that explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data will be presented…

Since the discovery of Channelrhodopsin and the first demonstration of photo-evoked action potentials in mammalian cells, optogenetics is progressively revolutionizing neuroscience research, opening perspectives both in fundamental and in medical research still unimaginable until few years ago.
Joint progress in light delivering…

Complex life above a certain size would not be possible without a circulatory system. Both plants and animals have developed vascular systems of striking complexity to solve the problem of nutrient delivery, waste removal, and information exchange. Vascular networks are intimately linked to the fitness of organisms. Despite their importance,…

I will survey some of the research of my group in areas that sit at the intersection of mechanics and biology. First, I will offer some perspective of how classical physics, and in particular both fluid mechanics and elasticity, as they are considered in modern engineering curricula, are well suited to materials-centric  studies of biology in…

As an animal moves in space and receives external sensory inputs, it must dynamically maintain the representations of its position and environment at all times. How the hippocampus, a brain area crucial for spatial representations, achieves this task, and manages possible conflicts between different inputs remains unclear. To study this…