|08/30/2018||Anthony Aportela / Yasemin Ozkan Aydin||Fenton / Bhamla|
|09/06/2018||Olga Shishkov||Hu Lab|
|09/13/2018||Thomas Spencer||Hu Lab|
|10/11/2018||David Ryoo||JC Gumbart|
|10/18/2018||Guanlin Li||Weitz group|
|11/01/2018||Alireza Zamani||Peter Yunker|
|11/08/2018||Michael Ryan||Harold Kim|
Fall 2018 Abstracts
Anthony Aportela / Yasemin Ozkan Aydin
Genetic approach to cardiac modeling (Anthony)
Cardiac Models allow us to better understand the dynamics that occur within a heart. Heart related death is the number one killer in the United States. With models we can better understand the things that harm us in an effort to prevent and treat them. However, the heart is a chaotic system, small changes in parameters can lead to vastly distinct solutions. Finding the right parameters takes a combination of time, experience, and luck, especially for models with many tens of parameters. To expedite this process it is useful to take inspiration from biology and use a genetic algorithm. This talk goes through the theory behind creating a genetic algorithm as well as it’s successes and failures when used to fit real world data
Dynamics of a blob (Yasemin)
Organisms across all length scales (from cells to humans) cluster and forms large social groups for evolutionary advantages. In some cases, aggregates exhibit and enable new functionalities: floating on water (fire ants), nest-building (bees) and mobbing predators (birds). In this talk, we describe a recent discovery of aggregation in flexible living organisms and discuss emergent mechanics, dynamics and collective behavior.
Fly larvae feed by forming a flowing fountain
Black solder fly larvae are edible maggots that are raised by startups all over the world as a source of sustainable protein. A larva competes with its thousands of neighbors to eat twice its body weight per day in decomposing organic waste. We investigate how the collective motion of an aggregation of larvae “pumps” larvae towards a piece of food by considering the feeding behaviors of larvae from individuals to groups of 60,000. We perform time-lapse photography and particle image velocimetry analysis of top and bottom side views of larvae in glass dishes. Around food, larvae from a fountain with their bodies where larvae crawl towards food through the middle of the fountain and fall down the sides once they are done eating. This distributes food between the individuals in the fountain, rather than only allowing a select few larvae to eat.
Sniffing Scaling Study for Superior Sensing
Mammals such as dogs are known for their keen sense of smell and have been relied upon for their ability to find odor sources. A key component to the mammalian sense of smell is the dynamic sniff cycle. We find the rate at which mammals sniff scales at approximately the same rate as their maximum possible sniff frequency. We rationalize this trend due to the limits of their respiratory anatomy and physiology. Lungs of all mammals are constrained to approximately the same pressure whereas the geometry of the system increases with body size. This scaling argument and other literature suggests that mammals sniff as quickly as possible. Conversely, we find through oscillatory wind tunnel experiments and computational simulations that lower sniffing frequencies provide better odor collection in straight, rectangular channels. We proceed from rectangular channels to investigating the effect of biological nasal cavity shapes helps to mitigate odor collection. We apply insights gleaned from our biological and experimental results to design an electronic nose pre-concentrator for improved chemical sensing.
The Various Views on Killing – or: Antagonistic Interactions in Bacterial Biofilms
Biofilms constitute a relevant part of the microbiome of living organisms. Typically, a vast diversity of different microbial species exists inside a biofilm. This poses a series of challenges as individuals must avoid predation and compete for resources, space, and survival. In response, microbial species have evolved a variety of cooperative and competitive strategies. One potential mechanism for antagonistic killing is the Type VI secretion system (T6SS), which is present in a wide range of Gram-negative species. The T6SS enables bacteria to onject fatal toxins into other bacteria as well as eukaryotic cells. here, I will present studies on biofilms consisting of two antagonistic V. cholerae strains, as they provide an experimentally controllable and practically relevant system of mutual killers. From bacterial assays, the antagonistic behavior of T6SS-active V. cholerae strains has been proven previously by counting the survival rate of bacteria after exposure to an T6SS-active strain. More detailed information on the activity in the biofilm has been gained from microscopy. It shows that such an antagonistic one-on-one interaction causes an initially well-mixed culture to phase separate, providing protection by number. However, in experiments the typical size of clonal patches stops changing much earlier than expected from numerical results, which assume on-contact killing and replication. Here, I will present results on the biological and physical processes at the interface between mutual killing strains of V. cholerae with T6SS. I discuss the relevance of these findings for how clonal patches do – and do not – change, and derive consequences for the role of T6SS in dense biofilms.
Behaviorally Organizing and Buzzing Robots (BOB Bots)
In recent years, collective behavior has become a widely researched topic. Social insects like fire ants and bees, birds, fish schools, etc. provide good experimentation platforms for probing such collective behavior problems such as self-assembly, construction and transport. Alongside biological experimentation, computational modelling has helped understand a few principles governing the emergence of intelligent swarm behaviors from really simple local agents. A relatively new technique to approach these questions is to develop robo- physical swarm platforms for experimentation. The talk is going to introduce one such swarm of robots (BOB Bots) that we designed to help us with two interesting collective problems: a) jamming in active matter collectives and b) self-assembly, organization and transport in low memory or memoryless systems. BOB Bots house a vibrational motor in a 3d printed case and has rudimentary sensing and computation capabilities. These Bots interact with the environment and other BOB bots at a very local level based on contact and light sensing. The stochastic locomotion of each robot with no external control and minimal sensing manifests itself into interesting emergent phenomenon.
Synchronization in Bacterial Colonies
Recently, synthetic biology has made significant progress in reliably engineering microbial biocircuits. Manipulating transcription networks can create gene regulatory feedback loops that mimic the functions of electrical circuits. The oscillator, which can be constructed from simple negative feedback, is one of the simplest circuits. A natural extension is an interacting colony of oscillators. Such a system can exhibit mutual synchronization, which, in addition to having interesting dynamical properties, is useful for in vivo applications.
In this talk, I will discuss a novel example of a synchronizing bacteria system, the synchronized lysis circuit. By using quorum sensing to couple individual E. coli cells, the bacteria colony can be programmed to collectively lyse at a critical population threshold. This results in oscillatory dynamics that effectively limit the population size. On larger scales, synchronization gives way to wave-like propagations characteristic of excitable media.
Lateral gate and accessory protein dynamics of the BAM complex
Outer membrane proteins (OMPs) in Gram-negative bacteria are transmembrane β-barrel proteins that are involved in nutrition transport, signal transduction and export of virulence factors. The complex responsible for insertion and assembly of OMPs is the β-barrel assembly machinery (BAM). BAM structures have now been solved for all member proteins individually, and in complex, revealing two conformational states. However, a detailed mechanism for OMP insertion by the BAM complex is still not known. Currently, there are two leading models for this insertion process based on features proximal to the seam between the N-terminal (β1) and C-terminal (β16) strands of the BamA β-barrel: the assisted model and the budding model. The assisted model claims that, due to the decreased hydrophobic region near the lateral gate, the nascent OMP inserts itself into the outer membrane. In contrast, the budding model claims that the lateral gate opens and forms a β-sheet hybrid with the nascent OMP. While both models are backed by experimental evidence, no conclusive study yet exists. To shed a light on this issue, we have performed molecular dynamics simulations to identify key interactions related to the insertion process. Using the previously identified crystal structures, we have carried out microsecond-long equilibrium simulations of BAM complex systems with an open or a closed lateral gate and with or without the lipoprotein BamB. We discovered that the laterally open structure is unstable in the absence of accessory proteins and the rotational movement of the accessory proteins drives lateral gate dynamics.
Why be Temperate: On the Fitness Benefits of Lysis vs. Lysogeny
Many viruses exclusively infect and kill (‘lyse’) their hosts, releasing new viral progeny. In contrast, temperate bacteriophages have multiple strategies to interact with their bacterial hosts, including lysis and lysogeny. In the lysogenic mode, viral genomes are integrated with the bacterial chromosome and then replicated along with the infected cells. Subsequently, viruses in the lysogenic mode can ‘induce’, and restart the lytic pathway. The deferral of lysis (and the immediate generation of virus particles) has led to a
long-standing question: why be temperate? Here, we explore the dependency of viral fitness on infection mode given variation in susceptible host abundance. In doing so, we present a model of temperate phage-host dynamics, including mechanistic processes of integration and induction. We use the next generation method and a novel application of Levins’ loop analysis to compute viral fitness in terms of the basic reproduction number. We compute contributions from all possible infectious transmission paths that start and finish with infectious cells, rather than in terms of virus particles. In doing so, we provide evidence that lysogeny is favored at low host abundances and lysis is favored at high host abundances. In addition, we find that induction should occur rarely when integration is favored, consistent with experimental observations. Finally, we examine the robustness of viral strategies that maximize fitness by studying the competition outcomes from viruses with different strategies including regimes where temperate strategies outperform exclusively lytic strategies. Altogether, our results provide new eco-evolutionary insights into the benefits of being temperate.
The wind around moth wings: how unsteady environments affect agility and aerodynamics
Natural environments create unsteady airflow when wind interacts with flowers, trees, and other obstacles. Most small flying animals rely on coherent, but unsteady structures to maintain lift like the ubiquitous leading edge vortex (LEV). Many insects flap at Reynolds numbers where the LEV can burst while remaining attached to the wing, but this has not yet been observed on a freely behaving animal. Hawk moths hover feed at flowers and must interact with environmental disturbances including the flower wake. Using a robotic flower we show that maneuverability suffers most at the vortex shedding frequencies in the flower wake. Since flight dynamics are altered but overall hovering persists, is the structure of the LEV disrupted by interaction with shed vortices? We examined the structure and persistence of the LEV using smoke visualization over the wings and thorax of hawkmoths in the roboflower wake. Although LEV bursting is expected at the Reynolds number relevant for hawkmoth flight, the LEV in the flower wake remains bound throughout the wingstroke with no apparent bursting. The LEV also maintains the same qualitative structure seen in steady air. To quantify these changes in the LEV throughout a wingstroke, we performed 3D particle tracking velocimetry (3D-PTV) in the wake of freely flying and tethered hawkmoths downstream of the 3D-printed flower. Capturing flight aerodynamics at the scale of flapping insects requires high spatial and temporal resolution. High wingbeat frequencies suggest aerodynamics may change on a millisecond timescale and wingspan is on the order of centimeters. Within wingbeat time resolution was obtained with a 60mJ/pulse Nd:YLF laser operating at 1kHz. High spatial resolution was achieved in the 90mm x 50 mm x 20mm illuminated volume using micron-sized particles. We found that the downwash produced in the wake of the hawkmoth dominates the flow in the flower wake. Next we plan to quantify vortex interaction between the LEV and the environment on the wing surface with across a systematic range of vortex shedding frequencies.
Biomechanics of Superflakes yeasts
The evolution of multicellular life from single-celled ancestors is one of the most radical shifts in the history of life on earth, and sets the stage for evolution of more complex life forms. Despite the significance of this transition, we know little about the process by which cells first assemble groups and form multicellular organisms. We study this problem experimentally; a single mutation in the ACE2 gene of Baker’s yeast S. cerevisiae prevents mother and daughter cells from separating after cellular division. These yeast clusters, called ‘snowflake’ yeast, comprise a few hundred cells and grow to a maximum diameter of 200 microns. To evolve larger multicellular size, snowflake yeast clusters must mitigate forces strong enough to fracture cell-cell bonds. After a year of artificial selection for larger multicellular size, five populations of snowflake yeast surprisingly evolved to grow to a maximum diameter of 1 mm. In this work we will investigate how nascent multicellular clusters evolve to overcome substantial mechanical constraints and dramatically increase their size.
Exploring the Plectonemic Response of DNA
Aided by proteins, DNA is condensed to a small volume in order to fit inside the nucleus of a cell. In the process, the DNA strand develops regions of superhelicity, leading to plectoneme formation. These higher order loops have consequences in gene expression and protein kinetics. Despite their importance, they are difficult to probe as they are short lived (~0.1 s) and too small to see with traditional optical microscopes. We propose using horizontal magnetic tweezers in conjunction with fluorescence microscopy to directly visualize and control the superhelical density and stretching force on a single DNA molecule. Thus far, we have managed to reproduce force extension curves and characteristic hat curves representative of single tethers and plectoneme formation. We plan to implement fluorescence in the near future to directly visualize plectonemes, allowing us to characterize their nucleation and displacement with the addition of crowding agents to better represent their environment in vivo.
Repulsive Forces at the Cell-Substratum Interface
Cell adhesion and its dynamic regulation lie at the heart of many fundamental biological functions, including cell migration and related processes like embryonic development, wound healing, cancer metastasis and more. Much attention has been given to adhesive elements, the molecular assemblies that anchor the cell to the substratum. However, it is less appreciated that, together with adhesions at the cell-substratum interface, hyaluronan-rich glycocalyx is often correlated with changes in cell adhesion state and migration. Our data address a long-standing hypothesis, by showing that hyaluronan regulates cell adhesion and thereby, mediates cell migration. This work directly fills a fundamental gap in our knowledge, suggesting a mechanism of the adhesion regulation, and providing insight into whether hyaluronan glycocalyx and adhesion complexes are complementary systems that co-orchestrate cell-extracellular matrix adhesion and migration.
No speaker. Thanksgiving Break.
Tell-tale hearts: descent into cardiac chaos
Proper contraction of cardiac muscle relies on the coordinated propagation of transmembrane voltage, and disturbances of this propagation can result in deadly cardiac arrhythmias such as fibrillation. Even in healthy tissue, high heart rates can drive the system to a cellular-level dynamical instability known as alternans, a period doubling bifurcation in action potential duration (APD), which is strongly associated with the onset of fibrillation and sudden cardiac death. A functional relationship between the APD and preceding diastolic interval (DI) known as the restitution hypothesis aims to predict the onset of alternans. Much theoretical effort based on the restitution hypothesis has aimed to suppress the onset of alternans through cardiac stimulation at a constant DI with very positive results; however, few experiments have addressed these predictions. In this talk, I will discuss comparative cardiac dynamics in the hearts of species including rabbit, dog, cat, pig, frog, zebrafish, snake, lizard, and alligator through the use of microelectrode recordings and optical mapping of fluorescent voltage and calcium signals across the heart’s surface. Furthermore, I will discuss a closed-loop system for performing constant DI control and the highly unexpected results.