Title: Constraints on cultures and characters

Professor Seppe Kuehn, University of Illinois at Urbana-Champaign
October 27, 2017 at 4pm in PAB 4-330

Abstract: Can we predict evolutionary and ecological dynamics in microbial communities?  In this talk I argue that understanding constraints on biological systems provides a path forward to build predictive, phenomenological models.  I present two vignettes which illustrate the power of elucidating constraints.  First, in Nature microbial populations are subjected to variable levels of nutrients.  Models of microbial growth stipulate that the rate of biomass production depends instantaneously on the levels of nutrients available.  To test this assumption we subject populations of bacteria to periodic pulses of nutrients (feast) and long periods of starvation (famine) with varying frequency and amplitude.  Exploiting precise measurements we show that that growth rate during feasts depends on the duration of famine.  Our results are explained by a simple phenomenological model and have important implications for understanding abundance dynamics in microbial communities. In second study we ask how constraints on phenotypic variation limit the capacity of organisms to adapt to multiple simultaneous selection pressures.  We select Escherichia coli for faster migration through a porous environment, a process which depends on both motility and growth. We find that a trade-off between swimming speed and growth rate constrains the evolution of faster migration. Evolving faster migration in rich medium results in slow growth and fast swimming, while evolution in minimal medium results in fast growth and slow swimming. A model of the evolutionary process shows that the genetic capacity of an organism to vary traits can qualitatively depend on its environment, which in turn alters its evolutionary trajectory [eLife, 2017].  We explore the possibility that phenotypic constraints and genetic architecture can provide a route to predicting evolutionary dynamics.

Title: Mathematical modeling of transport processes in cell biology

By Heather Zinn Brooks, University of Utah
October 13, 2017 at 4pm in PAB 4-330

Cells rely on combinations of diffusion and molecular motor transport of macromolecules for proper development and functionality. In this talk, I will present mathematical models of two scenarios where intracellular transport plays a key role. Using analysis of a model of partial differential equations, I show that synapse density maintenance in the ventral cord of C. elegans can be explained by a Turing-type mechanism, namely interactions of diffusion and actively transported proteins. I will then discuss a second scenario that shows the dark side of intracellular transport: molecular motors can be hijacked by viruses in order to travel more efficiently to the host cell's nucleus for replication. In this work, we derive an effective stochastic differential equation for viral transport to quantify first passage times to the nucleus.

Title: Antigen Affinity Discrimination in Germinal Center B-Cell Immune Synapses

Milos Knezevic, UCLA
October 6, 2017 at 4pm in PAB 4-330

Abstract: Efficient antibody responses need expansion of high affinity B cell clones. The initial stimulations of B cells occur when their B cell receptors (BCRs) bind to antigens found on the surfaces of antigen-presenting cells (APCs). These contacts lead to formation of immune synapses, which B cells use to extract antigen from the APCs. Typically B cells that express high-affinity BCRs obtain more antigen and compete better for T cell help. Immune synapses in naive and memory B cells form a large cluster of BCR-antigen complexes in the synapse center. Once this central cluster is assembled, B cells extract antigen from it via mechanical forces produced by the cortical cytoskeleton. However, in recent experiments it has been shown that germinal center (GC) B cells extract antigen by a distinct pathway which involves small peripheral clusters of BCR-antigen complexes. In this talk, we use Monte Carlo simulations to study pattern formation during GC B-cell – APC adhesion. We apply mechanical forces on BCR-antigen clusters above a certain threshold size, and investigate their effect on the quality of antigen affinity discrimination.

Title: Landau Theory for Assembly of Viral Capsids

Sanjay Dharmavaram, UCLA
September 22, 2017 at 4pm in PAB 4-330

The talk will discuss why the theory of the assembly of viral shells leads to fundamental problems with the Landau description of phase transitions. The talk will apply the Landau-Brazovskii theory for the solidification of chiral molecules on a spherical surface into an icosahedral density modulation. If assembly is based on assembling pentamer and hexamers then robust, weakly chiral icosahedral structures appear via first-order transitions. If it is based on the assembly of individual protein, then fragile icosahedral structures with a pronounced chiral character appear via weakly first-order or continuous transitions. Here, the icosahedral state is in close competition with states that have tetrahedral, octahedral and five-fold (D_5) symmetries. The application of the Landau theory of phase transitions to the problem of solidification on spherical surfaces requires allowing multiple irreducible representations of the symmetry group of the uniform phase to be realized at the transition point.

Encoding of distance, axis of travel, and topology at the juncture of hippocampal and posterior parietal systems for spatial mapping

Douglas Nitz, UC San Diego
June 20 2017, 4pm PAB 1-434

The subiculum and retrosplenial cortex together form a robust connection between hippocampal representations of position in the environment and posterior parietal cortex representations of position in route space. Our recent work examining the spatial firing properties of neurons within subiculum and retrosplenial cortex indicate that, in different ways, these structures encode conjunctions of spatial information concerning route spaces and their positioning and orientation in the larger environment. Furthermore, novel forms of spatial information encoding emerge in each structure. These forms include 'axis-tuning' and encoding of 'spatial analogies' in subiculum, and, in retrosplenial cortex, the encoding of position within route sub-spaces and distances between all route locations. The former are integrated temporally with the hippocampal CA1 sub-region through 'theta phase precession'. The latter, when considered in the context of retrosplenial encoding of head direction, could, in principle, form the basis for knowledge of overall path geometry. The results of these recent findings will be considered with respect to anatomical pathways that appear to represent the transformation of spatial cognition into action. 

Formation of two-dimensional DNA films at the air/water interface

Jaime Ruiz-Garcia, Autonomous University of San Luis Potosí, Mexico
May 26, 2017, 4pm PAB 4-330
The central dogma in Langmuir monolayers studies is that they are formed when amphiphilic molecules are deposited and spread spontaneously on the water surface to form a monomolecular film. A typical characteristic of these systems is that they are formed by molecules with a hydrophilic head group and a large hydrophobic tail, such as fatty acids, phospholipids, etc. In this talk, we will show that monomolecular films at the air/water interface can also be formed using water soluble molecules. DNA is a highly charged polyelectrolyte and it is considered to be completely soluble in pure water. We show that DNA can be trapped at the air/water interface and does not go back into a water subphase. DNA is trapped in an energy minimum at the interface, much bigger that KBT, that does not permit its return to the water subphase. Once at the interface, DNA molecules condense to form two-dimensional foam-like mesostructures. This condensation occurs without the presence of multivalent cations. At high density, the molecules form a remarkable monomolecular network. At the interface, DNA is only partially immersed in water, which originates that the chains get only partially charged, but the charges are of the same sign. Therefore, this can be considered another case of like-charge attraction, similar to that found in colloids in restricted geometries such as the air/water interface and between glass plates. However, the origin of the attractive part of the interaction potential is unknown. In addition, we found that DNA at the air/water interface can form large 2D tetratic phase domains. Both the DNA monomolecular networks and the tetratic phase domains are interesting from theoretical and application standpoints.

Odd viscosity in chiral active fluids

Anton Sousolv, Leiden University
May 19, 2017, 4pm PAB 4-330

Abstract: Chiral active fluids are materials composed of self-spinning rotors that continuously inject energy and angular momentum at the microscale. Out-of-equilibrium fluids with active-rotor constituents have been experimentally realized using nanoscale biomolecular motors, microscale active colloids, or macroscale driven chiral grains. I will discuss how chiral active fluids break both parity and time-reversal symmetries in their steady states, giving rise to a dissipationless linear-response coefficient called odd (equivalently, Hall) viscosity in their constitutive relations. This odd viscosity provides no energy dissipation, but can give rise to a transverse flow – for example within a hypersonic shock. Such a viscosity term has been previously examined in the context of electron fluids subject to a magnetic field. However, only in active fluids does odd viscosity: (i) arise out of equilibrium, (ii) always come accompanied by an antisymmetric stress, and (iii) become ill-defined in the regime in which active rotations are hindered by interactions. I will examine the origins of odd viscosity and suggest how this property may be exploited to buildmachines powered by active fluids.

Optimizing self-assembly kinetics for biomolecules and complex nanostructures

William Jacobs, Harvard University
April 14, 2017, 4pm PAB 4-330

Abstract: In a heterogeneous self-assembling system, such as a large biomolecule or nanostructure, there is no guarantee that the lowest-free-energy state will form.  Defects and mis-interactions among subunits often arise during a self-assembly reaction, particularly in systems comprising many distinct components.  As a result, if we wish to assemble complex nanostructures reliably, we need to design robust kinetic pathways to the target structures, and not focus  solely on their thermodynamic stabilities.  In this talk, I shall describe a theoretical approach to predicting self-assembly pathways, with applications to both engineered nanostructures and natural biomolecules.  First, I shall discuss design principles that can be used to tune the nucleation and growth rates of DNA 'bricks'.  These principles have crucial implications for low-defect self-assembly and the design of time-dependent experimental protocols.  Then, to highlight the biological importance of self-assembly kinetics, I shall present evidence that evolutionary selection has tuned ribosome translation rates to optimize the folding of globular proteins.

Dynamics of elastic waves on curved planar rods

Jonathan Matthew Kernes, UCLA
4pm PAB 4-330

Abstract: Lower dimensional elastic structures break isotropic symmetry of the material, introducing a preferred coordinate frame. Correspondingly, for an embedded structure the local tangential and normal components deformations respond in a separate but geometrically linked fashion. We exhibit the interaction between normal direction bending undulations, and tangential direction stretching deformations in the simplest case of a rod with local background radius of curvature. Curvature is found to decrease the availble oscillators in our system, as well as restrict the allowed frequencies.


Special Joint AMO/CM/CBP Seminar: Biomagnetic sensing with nitrogen vacancies in diamond

John Barry, Harvard University and MIT Lincoln Laboratory
March 3, 2017, 4pm PAB 1-434A

Abstract: Nitrogen vacancy (NV) color centers in diamond are rapidly emerging as a viable technology for quantum sensing. At the smallest scales, single NVs provide angstrom-scale spatial resolution with sensitivity sufficient for individual electron, proton, or protein detection. At much larger scales, bulk magnetometers harnessing large NV ensembles presently exhibit sensitivities surpassed only by SQUIDs and atomic vapor cells. Between these two limiting regimes, shallow surface layers of NVs allow for wide field-of-view magnetic imaging with diffraction-limited performance. The achieved combination of resolution and magnetic sensitivity remain unmatched for non-invasive imaging under ambient conditions, making solid state magnetic imaging favored for future investigations of various physical and biological phenomena. This talk presents progress towards one primary application: magnetic detection and imaging of action potentials from single neurons. We demonstrate this method using excised axons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to intact, live, opaque marine worms.  Extended-duration magnetic sensing is performed with no adverse effect. We discuss future steps to enable non-invasive imaging of functional mammalian neural networks in real time.

Statistical physics of molecular evolution: from gene regulation to the immune system

Armita Nourmohammad, Princeton University
March 3, 2017, 3pm PAB 4-330

A venerable question in evolutionary biology is: if the tape of life was replayed, would the outcome be the same? We do not know how evolutionary predictability relates to different molecular scales, ranging from genotypes (DNA and amino acids) to molecular phenotypes (functions such as protein activity). I discuss universal properties of molecular phenotypes, encoded by genotypes with large degrees of freedom, which allow for the predictive description of their evolution. Populations are often subject to time-dependent pressure from the environment. I introduce a non-equilibrium framework for adaptive evolution of molecular phenotypes in time-dependent conditions. As an example, I present strong evidence that environmental fluctuations drive the evolution of gene expression levels in Drosophila. Co-evolving populations reciprocally affect the fitness of each other, acting as time-dependent environments with feedback. I show evidence of co-adaptation between interacting cellular populations of HIV viruses and the antibody repertoire of a patient over the course of an infection. In particular, I discuss the conditions for emergence of broadly neutralizing antibodies, which are recognized as critical for designing an effective vaccine against HIV.

Step-by-step shape evolution of tubular solids by defect motion

Daniel Beller, Harvard University
February 24, 2017, 4:00pm PAB 4-330 

Abstract: Two-dimensional crystalline order on surfaces with cylindrical topology gives rise to helical lattices. This type of packing occurs in biology at many scales, from biofilaments to viral capsids to botany, as well as in carbon nanotubes and in colloidal crystals. Shape changes in the tubular surface generally require changes in the crystalline tessellation of the surface. This evolution can be undertaken step-by-step via the motion of elementary defect pairs through the tubular crystal. I will discuss the physics of plastic deformation in tubular crystals by the unbinding and glide separation of dislocation pairs. Through theory and simulation, this work examines how the tube’s radius and helicity affect, and are in turn altered by, the mechanics of dislocation glide. The system’s bending rigidity plays an important role, and can resist, arrest, or even reverse the deformations of tubes with small radii. I will also discuss the equilibrium shapes of tubes containing dislocations, with potential implications for biofilaments such as microtubules. 

Activity, specificity, selectivity: new approaches for micro-assembly

Carl Goodrich, Harvard University
February 10, 2017, 4:00pm PAB 4-330

Abstract: Biology is able to build remarkable machines through a combination of programmable interactions and specific energy input through small molecules (ATP). However, we are largely unable to manufacture artificial structures of comparable complexity at the microscopic scale. The development of specific DNA glues has revolutionized our ability to program interactions, but we have barely scratched the surface of what can be built. I will discuss new approaches for micro-assembly, focusing on the use of self-propelled particles (a potential alternative to ATP) to drive out-of-equilibrium assembly. Under the right conditions, for example, the motion of active colloids can be programmed to pull semiflexible filaments into topological structures such as braids and weaves. I will also discuss how DNA interactions can be used to program a selectively permeable gel. 

Aggregation of proteins: growth of glucagon fibrils and bacterial growth

Andrej Kosmrlj, Princeton University
February 3, 2017, 4:00pm PAB 4-330

Abstract: Misfolding and aggregation of peptides and proteins are the hallmarks of many human diseases. With the advancement of microscopes, it is now possible to observe the kinetics of individual aggregates and fibrils in vitro. Interestingly, in some cases the growth of fibrils is intermittent, where the periods of growth are interrupted by periods of stasis. In this talk I will focus on the intermittent fibrillation of glucagon and I will describe how E. coli bacteria deal with harmful aggregates of misfolded proteins. Glucagon is a peptide hormone that upregulates blood sugar levels and is used to treat diabetic patients in situations of acute hypoglycemia. When dissolved in a fluid state, glucagon can form fibrils and become useless, as the fibrils cannot be absorbed and used by the body. The observed intermittent growth of glucagon fibrils can be explained with a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers. The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well. Finally, I will discuss how E. coli bacteria deal with harmful aggregates of misfolded proteins that develop, when bacteria are under heat or antibiotic stress. In order to maximize the fitness of the whole population, bacteria distribute aggregates asymmetrically between their daughters, such that one daughter inherits the whole aggregate, while the other daughter receives none of it. Over time such asymmetric distribution of aggregates produces many “rejuvenated” bacteria with small aggregates that are quickly dividing at the expense of a few bacteria with large aggregates that are dividing very slowly.