Fall 2015 Schedule

Date      Speaker                            Lab

08/27    Claire Yanyan Ji            Flavio Fenton

&               Tingnan Zhang           Dan Goldman

09/03    Mark Kingsbury            Dan Goldman

09/10    Maksym Korablyov      JC Gumbart

09/17    Wenbin Wei                    Jennifer Curtis

09/24   Chen Rui                          David Hu

10/01    Perrin Schiebel               Dan Goldman

10/08   Luis Jover                       Joshua Weitz

10/15    Gable Wadsworth          Harold Kim

10/22    Bradford Taylor            Joshua Weitz

10/29    Patrick Chang               Jennifer Curtis

11/05    Jiyoun Jeong                 Harold Kim

11/12     Ram/Krishma              Flavio Fenton

11/19    Gorman Stock               JC Gumbart

12/03   Patricia Yang                David Hu

 

Fall 2015 Abstracts


27 August 2015

Claire Yanyan Ji
Modeling the electrical interaction between tissue and MIFI catheter

Abstract: Thermal ablation is a procedure to turn active tissues into electrically inactive scars in order to terminate abnormal signals in heart. The ablation catheter that delivers the current which is used to burn abnormal tissues can also be used in sensing electrical interaction between the tissue and the injected current. In this presentation I will compare experiment, modeling and theory to show how to use the voltage measured by the catheter to determine the contact between tissue and catheter.

Tingnan Zhang
Internship experience at Google working on compilers, software architecture and Chrome sandbox

 

03 September 2015

Mark Kingsbury
Two-foot interaction during bipedal walking over granular media

Abstract: Bipedal walking of humans and robots is well studied on ground where feet neither slip nor penetrate the substrate. In such situations, walking is characterized by a swing phase (during which one foot is lifted and the other is planted on the ground) and a double support phase (during which both feet are in contact with the ground). When walking through flowable media like sand or snow however, a finite duration double support phase must occur: of interest to us are such interactions that take place during the foot (and lower limb) intrusion and extrusion phases. In such phases, motion of the two feet relative to each other and the resultant drag forces on each foot will determine if a foot slips in the material, thus degrading the kinematic performance of the walker. To examine these issues, we study the locomotion of a planarized bipedal walking robot (1.6 kg, 40 cm tall) which can translate only in the vertical and fore-aft directions. The 8 motor robot (4 per limb) walks on a fluidized bed of poppy seeds at different granular compactions. The motors are controlled to generate gaits with varying foot insertion trajectories. An asymmetry within the robot’s gait allowed us to explore the differential slipping that can occur during the traditional double support phase in granular media. During this phase, when there is motion between the two feet relative to each other (as would occur in an asymmetric gait), only one foot will slip while the foot lower in the ground will remain planted because objects deeper in granular media experience proportionally higher drag forces. We define this slip as the “double support slip.” We modeled the robot in the Chrono simulation engine and used experimentally validated Resistive Force Theory to calculate the granular ground reaction forces on the feet and lower limbs. Even without inputting an asymmetry between the two steps, the simulated robot experienced slip during the intrusion phase in the granular media. The amount of slip depended on the angles of foot insertion. We define this slip as the intrusion slip. When adding the intrusion slip measured from simulation to the double support slip measured experimentally, we modeled the total slip that the asymmetrically stepping experimental robot experienced while walking over granular media. We conclude that the dynamics of bipedal walking over granular media can be strongly affected by differential slipping experienced during the two-foot interaction with the material.

 

10 September 2015

Maksym Korablyov
Studying viral capsid protein conformational changes with molecular dynamics

Abstract: In this work we applied two different molecular dynamics approaches to study two unrelated problems of viral capsid protein flexibility. In the first case we studied the change in shape of the viral capsid related to its maturation. Because maturation involves reverse synthesis of the DNA on the RNA template, the amount of negatively charged nucleic acid inside the core doubles. We studied the conformational changes in the viral capsid using Molecular Dynamics Flexible Fitting approach. Our findings show that viral core itself may be a viable target for drug design.
In the second case, we studied behaviour of the capsid protein dimer – a minimal assembly unit, in water using the special-purpose molecular dynamics supercomputer Anton developed by DE Shaw Research. Because of the features of its construction, Anton allows us to obtain trajectories approximately a hundred times longer than on general-purpose machines. A microsecond-long molecular dynamics trajectory revealed new movements of the protein invisible on a shorter timescale.

 

17 September 2015

Wenbin Wei
Polymer Degrafting Force and Molecular Counter

Abstract: In this work we applied two different molecular dynamics approaches to study two unrelated problems of viral capsid protein flexibility. In the first case we studied the change in shape of the viral capsid related to its maturation. Because maturation involves reverse synthesis of the DNA on the RNA template, the amount of negatively charged nucleic acid inside the core doubles. We studied the conformational changes in the viral capsid using Molecular Dynamics Flexible Fitting approach. Our findings show that viral core itself may be a viable target for drug design.
In the second case, we studied behaviour of the capsid protein dimer – a minimal assembly unit, in water using the special-purpose molecular dynamics supercomputer Anton developed by DE Shaw Research. Because of the features of its construction, Anton allows us to obtain trajectories approximately a hundred times longer than on general-purpose machines. A microsecond-long molecular dynamics trajectory revealed new movements of the protein invisible on a shorter timescale.

 

24 September 2015

Rui Chen
Beetle wings are inflatable origami

Abstract: Beetles keep their wings folded and protected under a hard shell. In times of danger, they must unfold them rapidly in order for them to fly to escape. Moreover, they must do so across a range of body mass, from 1 mg to 10 grams. How can they unfold their wings so quickly? We use high-speed videography to record wing unfolding times, which we relate to the geometry of the network of blood vessels in the wing. Larger beetles have longer unfolding times. Modeling of the flow of blood through the veins successfully accounts for the wing unfolding speed of large beetles. However, smaller beetles have anomalously short unfolding times, suggesting they have lower blood viscosity or higher driving pressure. The use of hydraulics to unfold complex objects may have implications in the design of micro-flying air vehicles.

 

01 October 2015

Perrin Schiebel
Slithering on sand: kinematics and controls for success on granular media

Abstract: Elongate, legless organisms, such as snakes, seemingly use simple body undulations to move on and within deformable substrates like sand. Previously, we have gained insight into the response of granular media (GM) to subsurface intrusion and used this understanding to find principles of subsurface undulatory locomotion. However, our knowledge of the physics of GM at the surface is limited. Therefore, when we challenged a variety of snake species to travel across the surface of a GM we found that performance was widely variable–ranging from efficient movement to complete failure–without an immediately obvious connection between various locomotor strategies and success. To understand what factors contribute to successful locomotion on challenging GM substrates, we focused on the study of a desert-dwelling snake Chionactis occipitalis (the Mojave Shovel-nose snake). We collected high-speed video of Chionactis (N = 10) moving on ~0.3 mm glass particles (a similar size to the GM in its natural habitat) and digitized the snake body for analysis. Using the organism studies in combination with resistive force theory calculations, GM drag experiments, and tests of a physical model (a snake-like robot), we find several factors which, acting together, contribute to animal performance; the body kinematics—targeting an ideal waveform, the ability to lift portions off of the substrate, and the properties of the GM. Based on the sensitive nature of the relationship between these factors, we hypothesize that having an element of force-based control, where the waveform is modulated in response to the forces acting between the body and the environment, is necessary for successful locomotion on flowing, granular substrates.

 

08 October 2015

Luis Jover
Inferring who infects whom in host-phage systems

Abstract: Bacteria and their viral parasites, i.e., phages, are found in natural environments from oceans, soils to the human gut. There are an estimated 1030 bacteria on Earth, with estimates of phages approximately 10-fold higher . Phages are not only abundant, but they are also key players in ecosystems. For example, phages can be responsible for a significant portion of microbial mortality, e.g., with estimates ranging from 20%-80%. These estimates of lysis are at the community scale. However, individual phages infect a subset of bacteria in a community. Quantifying who infects whom in a community is essential to understand how the individual-based traits affect ecosystem functions in complex environments. Phage host range has been traditionally determined using plaque essay which relay on the ability to isolate the host and are hard to scale up to community-level analysis with hundreds or even thousands of potential interactions. In this ongoing project we propose an alternate way of determining host-phage infection networks from measurements of the densities in experiments where several host and viruses interact

15 October 2015

Gable Wadsworth
Quantification of RNA Transcript level in single yeast cells

Abstract: Quantitative determination of the copy number of RNA transcripts in single cells is crucial to understand the genotype-phenotype connection.  mRNA FISH (Fluorescence In Situ Hybridization) is a popular technique used to quantify mRNA transcripts in many organisms including Saccharomyces Cerevisiae.  This technique relies on concentrating multiple fluorescent dyes on the target mRNA by DNA-RNA hybridization.  The downside to this protocol are the long mRNA that the DNA probe set needs to occupy and the cost of the modified probes.  We propose a new RNA FISH technique that utilizes a single 24-nucleotide DNA probe labeled with a single fluorophore. We demonstrate single-fluorophore sensitivity of this method  with both constitutive and inducible genes in budding yeast, and determine the false negative rate to be ~17%. The technique presented offers a cost effective and efficient means of quantifying short RNA transcripts at the single cell level.

 

22 October 2015

Bradford Taylor
Emergence of elevated levels of coinfection spatial host-virus dynamics

Abstract: Coinfection, when multiple viruses infect the same host cell, allows viruses to directly interact. This can alter ecological dynamics by varying burst sizes and complicate viral evolutionary dynamics through viral sex. Despite the well-documented effects of coinfection in vitro less is know about the effects in vivo and how these effects scale up to a population level. In this talk, I use an individual based spatial model to explore the rates and magnitude of coinfection. By varying the adsorption rate of viruses, different spatial patterns emerge. As the populations become clustered spatially the rates of coinfection increase when compared to expectations from the mean field model. Additionally, a larger fraction of the population are infected by more viruses than in the mean field model. These phenomena occur because of strong spatial correlation between hosts and viral populations in the clustered environments. Ultimately, this work suggests that coinfection can be a major factor in biofilms, which are naturally occurring bacteria-dense environments

 

29 October 2015

Patrick Chang
Cell Adhesion Strength Decreases due to Tethered Polymer Cushions  

Abstract: Cellular adhesion has been subjected to intense studies over the past several decades due to its importance in crucial physiological events including embryonic development, wound healing, cell migration, cell proliferation, synaptogenesis and cancer metastasis. One common but understudied theme in all of these systems is the presence of excess hyaluronan and proteoglycan. In particular, these molecular components often appear grafted to the cell surface in the form of the pericellular matrix (or perineuronal net on neurons). In this study, we test the hypothesis that pericellular matrix is expressed in patches beneath the cell, working in conjugation with integrin-mediated adhesion (focal contacts) to mediate cell adhesion. We present quantitative measurements of cell adhesion strength of cells with pericellular matrix before and after its degradation with various enzymes. We find that after partial digestion of proteoglycans, which significantly swell the polymers, the cell adhesion strength increases by a factor of two. These data represent the first quantitative measurements of the influence of pericellular matrix on cell adhesion and provide concrete evidence in support of the frequently cited but unproven statement that the polymer cushion provided by the surface-grafted hyaluronan inhibits or weakens cell adhesion. Future studies in our lab will focus on how critical this mechanism is in facilitating migration and proliferation in cancer.

 

05 November 2015

Jiyoun Jeong (JJ)
The effect of local melting of DNA on DNA loop formation

Abstract: Statistical mechanics of double-stranded DNA (dsDNA) is well described by the wormlike chain model (WLC) which assumes a harmonic bending potential. Such smooth bending potential may no longer be valid for large bending angles to form small loops (< 100 bp). Instead, DNA may rely on rare structural transitions such as local melting (opening) of base pairs to lower the energetic cost. In theory, open base pairs called bubbles can increase the looping probability of short DNA molecules by a few orders of magnitude, but a robust experimental validation of this theoretical prediction is lacking. Here, we investigated the correlation between local melting probability and looping dynamics of dsDNA using single-molecule fluorescence resonance energy transfer (FRET). We designed two groups of short DNA molecules with low and high melting probabilities around their center and measured their looping and unlooping rates in equilibrium. Our data allow rigorous tests of meltable wormlike chain (MWLC) models at short length scales for setting the lower limit for the free energy of bubble formation.

 

12 November 2015

Ramprasath Rajagopal (Ram)
Filter wheel for Multi-Signal Optical Mapping experiments

Abstract: Optical Mapping has been successfully used to measure electrophysiological signals like membrane potential and intracellular calcium. Dual camera systems have been devised in order record two signals simultaneously but such systems have not been able to be extended to measure more signals. We present a single camera filter wheel system capable of multiple signal recording. It consists of a custom made wheel with filters mounted in an alternating fashion. The wheel is synchronized with a camera to guarantee that only one filter will be present in the optical path during an exposure period and that no filters are skipped. The system is capable of operating at speeds of up to 1000fps. We utilized this system to  record Vm and Ca signals of a rabbit heart under various pacing protocols in order to verify operation.

Krishma Singal
Solving Mazes using Reaction Diffusion Equations

Abstract: Excitable systems driven by reaction diffusion equations have been shown to not only find solutions to mazes but to also to find the shortest path between the beginning and the end of the maze. In this talk we describe how we can use the Fitzhugh-Nagumo model, a generic model for excitable media, to solve a maze by varying the basin of attraction of its two fixed points. We demonstrate how two dimensional mazes are solved numerically using a Java Applet and then accelerated to run in real time by using graphic processors (GPUs). An application of this work is shown by guiding phototactic brine shrimp through a maze solved by the algorithm. Once the path is obtained, an Arduino directs the shrimp through the maze using lights from LEDs placed at the floor of the Maze. This method running in real time could be eventually used for guiding robots and cars through traffic.

 

19 November 2015

Gorman Stock
Pore Formation and Dynamics of CFTR

Abstract: Due to its importance in human health, the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein has been studied rigorously for the last 25 years. Even under meticulous study, a high-resolution structure of full length CFTR has yet to be resolved, but many CFTR homology models have been created in an attempt to alleviate this issue. To characterize the dynamics of this recalcitrant protein we have performed all-atom equilibrium Molecular Dynamics on a recently published and experimentally verified homology model of CFTR. In order to generate different starting states we have performed MD flexible fitting (MDFF) using structural data from a 9-Å cryo-EM map of CFTR in a two-dimensional crystal (Rosenberg et al., 2011). It is unclear which state, open or closed, that this map represents with dimerized Nucleotide Binding Domains (NBDs) within an environment lacking ATP. Crystal contacts may be responsible for the unusual conformation, as the largest structural differences from the original model are found there. Within our simulations, each of the fitted models retains various known open-state characteristics, although pore analysis shows the channel to be closed. The validity and dynamics of this homology model and its corresponding MDFF fits will be evaluated via a collection of conformational and experimental parameters, in an attempt to deduce structure-function relationships of CFTR.

 

03 December 2015

Patricia Yang
The hydrodynamic of digestion

Abstract: Despite the significance of gastrointestinal tract to human health, the physics of digestion remain poorly understood.  In this talk, we will discuss the transportation of processed food in rectum and small intestine.  We filmed the defecation event from cats to elephants.  All mammals defecate over nearly constant duration of 15 ± 12 seconds (N=16).  We rationalize the trend by the non-isometric dimension of rectum and the lubrication system on the wall of rectum.  We also filmed the motion of small intestine in vivo on rats.   The radial intestinal contraction is function of distance from stomach.  From stomach to cecum, the contraction frequency increases three folds with 80% decrease in amplitude as processed food moved distally.  The gas fraction of processed food increased from 0% to 90% in the distal portion.  These bubbles are the results of the generation of gas from microbial activity.  Bubbles decrease the effective cross-sectional area of the intestine, causing contractions of the wall to increase the velocity of the processing food, and the rate of mixing.   Our findings may help to diagnose digestive diseases and drug delivery mechanism for humans.