Eukaryotic cells contain organelle systems that organize and distribute molecular components. In this talk we will explore two such systems: mitochondria and the endoplasmic reticulum (ER), both of which form extensively networked architectures that span across the cell. While functionally distinct, both of these organelles give rise to…
For stable navigation, animals must coordinate ongoing sensory acquisition with motor output. Sensory acquisition can be tuned by active movement of sensors, increasing efficiency, volume or accuracy of sensory information. Further, additional information from several sensory modalities can contribute to stable movement, and influence motor…
I study how organisms integrate sensory information from multiple modalities across time and space to make decisions in complex naturalistic environments. My end goal is twofold: to understand how brains process sensory information, and to generate new, bioinspired, algorithms for engineered systems that enable the kind of resilience…
During morphogenesis, tissues integrate mechanical and biochemical signals to drive organ-scale geometric transformations. Understanding the dynamic interplay between genetic patterning, mechanical forces, and tissue geometry requires a physical framework that connects cell interactions to tissue shape change. Inner organs such as the gut and…
The concepts of energy and energy landscapes have been central to the understanding of many types of neural network computation. As Hopfield illustrated in the 1980's, generalizing the homogenous Ising model of magnetism to allow individually tunable symmetric point-to-point interactions yields a beautiful mathematical metaphor for…
Protein expression levels optimize cell fitness: Too low an expression level of essential proteins will slow growth by compromising essential processes; whereas overexpression slows growth by increasing the metabolic load. This trade-off naively predicts that cells maximize their fitness by sufficiency, expressing just enough of each essential…
The brain and body are inextricable in solving the pressing challenges faced by the animal. I will talk about our ongoing work with collaborators to build embodied models of the brain, where the nervous system interfaces explicitly with models of the body, including its kinematics, dynamics, and biomechanics. Our models are agent-based and…
Iron, despite its abundance in Earth's crust, remains a critical limiting nutrient for microbial growth due to its poor bioavailability. To acquire iron, most microbes produce siderophores — diverse small molecules with high iron-binding affinities. These siderophore-iron complexes are specifically recognized and uptaken by corresponding…
Molecular mechanisms that control cell growth and division enable bacteria and other microorganisms to maintain a narrow range of cell sizes within a population. While the control of cell size is ubiquitous in biology, the evolutionary benefit of maintaining a characteristic cell size is not understood in detail. In this talk, I will analyze…
How do brains compute? The Drosophila (fruit fly) larva is a small, semi-transparent crawling organism with about 10,000 neurons, compared to 100 billion in humans and 100 million in mice. Despite this simplicity, the larva carries out information-processing tasks, including navigation – moving towards a favorable location based on information…
Bacteria live complicated lives, in which they must swim through fluids of varying viscosities and interact with surfaces, sediment, and other cells. Accordingly, flagellar systems have evolved adaptive mechanisms to facilitate motility through a wide range of complex environments. At the molecular level, we characterize…
Movement control relies on continuously mapping sensory inputs to movement parameters, allowing an animal to compare its posture with its behavioral goals. This mapping must balance mechanical stability with the flexibility needed for goal-directed behavior in uncertain environments. In my lab, we investigate how self-generated visual…
Tangled active filaments are ubiquitous in nature, from chromosomal DNA and cilia carpets to root networks and worm collectives. How activity and elasticity facilitate collective topological transformations in living tangled matter is not well understood. In this talk, I will share our discoveries on why aquatic worms braid, tangle, and knot…
Systems neuroscience has traditionally progressed by recording neural activity and correlating it with external stimuli or behavior. While this approach has led to many key discoveries, it inherently requires a priori assumptions about the identity of the encoded variables. Recent advances in large-scale neuronal recordings in behaving animals…
Recent breakthroughs in experimental neuroscience and machine learning have opened new frontiers in understanding the computational principles governing neural circuits and artificial neural networks (ANNs). Both biological and artificial systems exhibit an astonishing degree of orchestrated information processing capabilities across multiple…
The human brain consists of billions of neurons, most of which communicate with each other by releasing different kinds of neuromodulators through chemical synapses, and therefore is able to control different physiological functions like perception, motion, learning and memory. To dissect the mechanism underlying how brain take part in…
Neurons often exhibit considerable fluctuations in their spontaneous (stimulus-free) activity, characterized by correlation functions. Neurons also react to time-dependent stimuli described by response functions. Because the neural raison d'etre is information processing and transmission (shaped by both their fluctuation and response properties…
Microbes have evolved genetically encoded machinery enabling them to utilize the abundant redox‐active molecules and extracellular minerals. Recently, the machinery enabling these redox reactions have been leveraged for interfacing cells and biomolecules with electrical circuits for biotechnological applications in energy harvesting, chemical…
Most proteins in the cell are only marginally stable, to allow their flexibility and plasticity and ultimately their easy recycling. The downside is the sensitivity of the structure of proteins to perturbations, in the form of environmental stresses and/or mutation, and the ensuing aggregation, which is in general toxic to all organisms.
Chirality is prevalent in nature and plays a crucial role in contexts ranging from left-right symmetry breaking in animal development to shaping material properties in synthetic systems. In this talk, I will discuss how chirality can emerge in multicellular systems, and how collectives of chiral particles exhibit novel material properties such…
Please join CPBF Center Directors Bill and Josh for an update on the state of the center.
Location: Joseph Henry Room (Jadwin Hall)
Circadian clocks regulate the timing of various behavioral and physiological activities in most organisms on a 24-hr scale such that they are phased appropriately to external, cyclic changes in the environment. The clock neuronal network in Drosophila melanogaster is comprised of ~150 neurons distributed bilaterally in the brain,…
Many of the physical processes in a cell consume energy, but we are only beginning to understand how these costs have influenced the course of evolution. Biology is strewn with counter-intuitively complex mechanisms whose evolutionary predecessors must have consumed significant energy resources without any clear fitness benefit. So…
In recent decades, much progress has been made in understanding how genes within cells contribute to organ-specific fates or disease phenotypes. However, it is becoming more widely acknowledged that increasing understanding at the molecular scale has not been sufficient to fully grasp how tissues comprised of thousands of cells generate their…
Pseudomonas aeruginosa is an opportunistic bacterial pathogen. Most P. aeruginosa isolates are infected by a filamentous virus (phage) called Pf. At sites of infection, filamentous Pf virions accumulate where they increase mucus viscosity, promote bacterial colonization, and directly stimulate innate anti-viral immune…
Groups of cells of all kinds work together as part of multicellular behaviors ranging from collective migration to development. These behaviors are coordinated at the level of single cells, where information about other cells and the environment are encoded in intracellular signaling dynamics that then drive cellular-level behaviors. We face…
Growth is central to life, shaping physiology, ecology, and evolution. In this talk, I discuss our efforts to elucidate the causes and consequences of bacterial growth across scales. Starting from resource allocation models and the molecular and energetic demands of protein synthesis, I first introduce how bacterial cells adjust their…
Behavioral strategies employed for chemotaxis have been studied across phyla, but the neural computations underlying navigational decisions remain elusive. By combining electrophysiology, quantitative behavioral analysis and computational modeling, we explore how olfactory signals experienced during free motion are processed by the olfactory…
Animal behaviors are complex and hierarchical spatiotemporal patterns. In the popular model organism Caenorhabditis elegans, behavioral sequences on a slower timescale emerge from ordered and flexible transitions between different motor states, such as forward movement, reversal, and turn. On a faster timescale, intricate head…
One governing principle of the microscopic world is "predictable randomness," where snapshots of a fluctuating process may appear random, but the average outcome of the process is predictable. An exciting frontier in biological physics is evaluating if predictable randomness extends to more complex, multi-component biophysical systems, such as…
Goal-reaching problems are ubiquitous in both the natural and engineered world. While learning to achieve goals is often considered an aspect of intelligence in biological systems, it is challenging to design practical algorithms for learning such behavior in high-dimensional environments. In this talk, I'll discuss recent work on contrastive…
The dynamic assembly and disassembly of the cytoskeleton can create waves and oscillations that are critical to cell migration and other important cell behaviors. Chemical signals have been found to trigger and steer these waves, facilitating the guidance e.g. of immune cells to their target. Here we consider the role of these…
In 1974 Purcell authored a paper “Life at Low Reynolds Number” to describe the counterintuitive world of microscopic organisms in which viscous dissipation so dominates inertia that “coasting” is impossible, and that the geometry of a path in an internal movement space dominates self-propulsion. It is typically assumed that a key difference…
Neural responses in association brain areas during cognitive tasks are heterogeneous, and the widespread assumption is that this heterogeneity reflects complex dynamics involved in cognition. However, the complexity may arise from a fundamentally different coding principle: the collective dynamics of a neural population encode simple…
Deep in the ocean or underground, where there is no oxygen, Geobacter “breathe” by projecting tiny hair-like protein filaments called "nanowires" into the soil, to dispose of excess electrons resulting from the conversion of nutrients to energy, cleaning up radioactive sites. Although it is long known that Geobacter use…
Recent advances in electrophysiology and optical imaging technologies enable recordings in behaving animals from hundreds or even thousands of neurons simultaneously. Since neural coding, computation, and communication rely on coordinated activity patterns across large cell populations, such data facilitate the study of the global structure of…
The interior of cells contains numerous components that need to be carefully organized in space to fulfill a wide range of biological functions. The most widespread form of intracellular compartments completely lack membranes. In the place of membranes, these compartments—so called biomolecular condensates—are sustained and segregated in space…
Earth’s atmosphere provides a thin barrier to the severe conditions of space. Globally, terrestrial microorganisms from our planet’s surface move through and interact with the blanketing atmosphere, analogous to how marine microbes drift through vast oceans. Whereas a century of exploration has allowed oceanographers to characterize…
TBA
Nanofluidic devices, e.g. based on nanochannels or nanopores, are networks of fluid-filled structures on a chip with dimensions ~1-100 nm. These dimensions are on order of molecular length scales, giving rise to the ability to directly analyze, manipulate and confine single biomolecules. In this talk I will focus on two different…
Infectious disease-causing pathogens have plagued humanity since antiquity, and the COVID-19 pandemic has been a vivid reminder of this perpetual existential threat. Vaccination has saved more lives than any other medical procedure, and effective vaccines have helped control the COVID-19 pandemic. However, we do not have effective vaccines…
In the first part of my talk, I will focus on mechanisms that regulate interactions between brain regions and describe how state-dependent frontal cortex dynamics can gate information flow from the sensory cortex during decision-making in mice.
In the second part, I will focus on information flow within the frontal cortex…
The actomyosin cytoskeleton is a naturally occurring active gel found in virtually all mammalian cells. Its ability to contract allows cells to move, change shape, exert force, sense stiffness, and maintain constant tension. In order for the “hardware” of actomyosin gels to support such a diverse set of mechanical tasks, it is tightly coupled…
Volume or 3D electron microscopy EM continues to expand its potential for imaging ever larger biological entities. Images from diamond knife cut sections launched the field of volume EM. An alternative of imaging the sequentially cut block face offered easier use and registration. FIB-SEM or Focused Ion Beam Scanning Electron…
Cell migration is a critical process underlying proper tissue maintenance. While a soft nucleus allows a cell to squeeze through small pores, the resulting physical stress can lead to nuclear damage and genomic variability. We have shown that the cytoskeletal intermediate filament protein vimentin protects against DNA damage…
Aggregations are common in biological systems at a range of scales and may be driven by exogenous constraints such as environmental heterogeneity and resource availability or by “self-organizing” interactions among individuals. One mechanism leading to self-organized animal aggregations is captured by Hamilton’s “selfish herd” hypothesis, which…
Super-resolution optical microscopy has become a powerful tool to study the nanoscale spatial distribution of molecules of interest in biological cells, tissues and other structures over the last years. Imaging these distributions in the context of other molecules or the general structural context is, however, still challenging. I will present…
In this talk, we propose to decipher the activity of neural networks via a “multiply and conquer” approach. This approach considers limit networks made of infinitely many replicas with the same basic neural structure. The key point is that these so-called replica-mean-field networks are in fact simplified, tractable versions of neural networks…
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…
Flies are among nature’s most agile flying creatures. This exquisite maneuverability is due in part to their possession of specialized mechanosensory organs known as the halteres. The halteres are evolved from the hindwings and provide flies with dynamic mechanosensory feedback on a wingstroke-to-wingstroke basis. Additionally, halteres are…
During early development gene expression patterns progressively emerge as cell fates are determined and the embryo takes form. The regulation of patterning occurs across a broad range of spatial and temporal scales. These scales range from the molecular scale dynamics of regulatory proteins binding to genomic loci to activate or repress…
The urgency to probe biological dynamics is impeded by a major challenge: the large dynamic range of biological processes—interactions of molecules within milliseconds can lead to changes across the whole-organism over days to years. It calls for measurements with both high spatiotemporal resolution and large-scale long-term coverage. However,…
Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop extruding cohesins. These loops and domains are thought to play critical roles in regulating gene expression by regulating long-range enhancer-promoter interactions. But whether CTCF/cohesin loops are stable or dynamic structures was…
In the event of metastatic disease, emergence of a lesion can occur at varying intervals from diagnosis and in some cases following successful treatment of the primary tumor. Genetic factors that drive metastatic progression have been identified, such as those involved in cell adhesion, signaling, extravasation and metabolism. However,…
Nov 1, 2022, 9:00 am – Nov 2, 2022, 5:00 pm
Location
Joseph Henry Room - Jadwin Hall
Sponsor
CPBF and NSF
We are interested in how physics at the colloidal scale instantiate life in biological cells. While principles from physics have driven recent paradigm shifts in how collective biomolecular behaviors orchestrate life, many mechanistic aspects of e.g. transcription, translation, and condensation remain mysterious because…
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…
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…