Eric Sembrat's Test Bonanza

The viruses that infect bacteria have a hallowed position in the development of modern biology, and once inspired Max Delbruck refer to them as "the atom of biology".  Recently, these viruses have become the subject of intensive physical investigation.  Using single-molecule techniques, it is actually possible to watch these viruses in the act of packing  and ejecting their DNA.    This talk will begin with a general introduction to viruses and their life cycles and will then focus on simple physical arguments about the forces that attend viral DNA packaging and ejection, predictions about the ejection process and single-molecule measurements of ejection itself.

Many different types of biological cells have the capability of sensing and generating mechanical forces.  These biophysical properties of cells are utilized for many different aspects of cell physiology, including cell migration and division as well as building multi-cellular assemblies.  To a large degree, the active mechanical behavior of cells is regulated by the filamentous actin (F-actin) cytoskeleton.  F-actin is a semi-flexible biopolymer that forms the basis of larger length scale structures in the cell through the action of other proteins that regulate assembly, cross-linking and force generation. 

Nearly all of these processes are driven far from thermal equilibrium by processes that rely on the consumption of chemical energy to regulate the spatial and temporal organization of network mechanics and force generation. To elucidate the physical properties of the actin cytoskeleton, we have studied the dynamics and biophysical properties of actin networks formed with myosin motors both in live cells and reconstituted networks of purified proteins.  A common feature among both actin/myosin and adhesive structures is that their stability and mechanics is highly tuned based on the amount of external tension.  This property enables rapid remodeling under low tension, but stabilizes the structures as forces are increases.   Thus, cellular materials provide insight into design principles that are utilized by highly adaptive matter.

Neutron stars are observed to rotate as fast as 716 Hz. Astrophysicists believe that they are spun-up by accretion of matter and angular momentum in binary star systems. However, the "r-mode" instability of rotating neutron stars, which is driven by gravitational radiation reaction, appears to prevent spin up via accretion to rotation frequencies above about 350 Hz.

We all know that modern science is undergoing a profound transformation as it aims to tackle the complex problems of the 21st Century.  It is
becoming highly collaborative; problems as diverse as climate change, renewable energy, or the origin of gamma-ray bursts require understanding
processes that no single group or community alone has the skills to address. At the same time, after centuries of little change, compute, data, and network environments have grown by 9-12 orders of magnitude in the last few decades.  Moreover, science is not only compute-intensive but is dominated now by data-intensive methods.  This dramatic change in the culture and methodology of science will require a much more integrated and comprehensive approach to development and deployment of hardware, software, and algorithmic tools and environments supporting research, education, and increasingly collaboration across disciplines.

Most biological processes are mediated by mediated by protein association, and often are under kinetic rather than thermodynamic control. We have developed the transient-complex theory for protein association, which presents a framework for elucidating the mechanisms of protein association and for predicting the association rates. The transient complex refers to an intermediate along the association process, in which the two associating molecules have near-native separation and relative orientation but have yet to form the short-range specific interactions of the native complex. Our theory rationalizes the variations in association rates over 10 orders of magnitudes and gives accurate prediction of the association rates based on the structures of the native complexes. In the cellular context, association processes occur in the presence of a high concentration of background macromolecules. We have developed methods to model the effects of the crowded cellular environments on the affinities and rate constants of protein association. These studies allow us to achieve a quantitative understanding of biological processes in the cellular context, based on fundamental physical principles.

"From Cardiac Cells to Genetic Regulatory Networks"
R. Grosu, G. Batt, F. Fenton, J. Glimm, C. Le Guernic, S.A. Smolka, and E. Bartocci

A fundamental question in the treatment of cardiac disorders, such as tachycardia and fibrillation, is under what circumstances does such a disorder arise? To answer to this question, we develop a multiaffine hybrid automaton (MHA) cardiac-cell model, and restate the original question as one of identication of the parameter ranges under which the MHA model accurately reproduces the disorder. The MHA model is obtained from the minimal cardiac model of Fenton by first bringing it into the form of a canonical, genetic regulatory network, and then linearizing its sigmoidal switches, in an optimal way. By leveraging the Rovergene tool for genetic regulatory networks, we are then able to successfully identify the parameter ranges of interest.

To view and/or participate in the webinar from wherever you are, click on:
evo.caltech.edu/evoNext/koala.jnlp?meeting=MDMaM8292nDIDB999tD99D

A cell is not just a small test tube in which biochemical reactions take place, but it also has a complex and highly dynamic mechanical structure. I will discuss the underlying physical principles that govern cellular mechanics on the nanoscale, and explore how DNA mechanics, on its own and within the context of a heavily crowded, constrained and perpetually fluctuating cellular environment, affects biological function. For example, forces of less than hundred femtonewtons can mechanically switch genes on and off by preventing the formation of regulatory DNA-protein complexes. Special emphasis will be placed on the role of intracellular fluctuations and noise, as our data indicate that active non-equilibrium fluctuations from molecular motor action, as opposed to purely thermal noise, may play a crucial role in efficiently assembling the genetic machinery.

A quantum computer uses superposition states to accomplish tasks (e.g., database search and factoring of integers) more efficiently than any known classical computing strategy. In conventional registers for quantum information processing, quantum bits are associated with individual two-level quantum systems. Separate addressing and interaction with these systems permit one-bit gates, while an interaction between systems is needed
to accomplish two-bit gates.

The seminar will review recent theoretical proposals to implement quantum computing in collective excitation degrees of freedom in ensembles of
identical quantum systems. In these proposals one does not address individual particles, but one needs a suitable global interaction to perform
quantum logic operations in the system.

Such a global interaction exists in hybrid systems where large ensembles of electron or nuclear spins in a solid are collectively coupled to
superconducting qubit elements via a quantized cavity field. These physical components are optimal for the very different tasks of stable memory and
rapid processing functions, needed in a quantum computer  The main ideas of the spin-ensemble encoding and impressive preliminary proof-of-principle
experiments will be discussed.

In the framework of the Fitzhugh-Nagumo kinetics and the oscillatory recovery in excitable media, we present a new type of meandering of the spiral waves, which leads to spiral break up and spatiotemporal chaos. The tip of the spiral follows an outward spiral-like trajectory and the spiral core expands in time. This type of destabilization of simple rotation is attributed to the effects of curvature and the wave-fronts interactions in the case of oscillatory damped recovery to the rest state. This model offers a new route to and caricature for cardiac fibrillation, and when we apply the feedback resonant drift method, for defibrillation all wave activity gets eliminated at the unexcitable boundaries.