Seminars are held
on Tuesdays from 4:00 p.m. at 114 Dana Research Center, with
refreshments served beforehand at 3:45. All are welcome to
attend!
May 28th, 2002
Title:"How do we
learn? Learning theory in the 21st Century."
By: Donna Qualters, PhD
Director for Center for Effective
University Teaching
Northeastern University
ABSTRACT:
Is the lecture dead? Who's responsible for learning? How can I
possibly cover material AND do active learning in a quarter? Modern
science has opened the window to the brain and in doing so has
revealed some interesting facts about why and how people learn. This
seminar will explore the most recent learning theories such as
social cognition, brain based/neuroscience, multiple intelligences,
and constructivism and explore the implications and impact of these
theories on a modern day science classroom.
May 14 th, 2002
Title:"Localized
States and Biophysics"
By: Professor
David Nelson
Department Of Physics
Harvard
University
ABSTRACT:
Localized and extended states play important roles in a number of
biological problems. We discuss in some detail the delocalization in
DNA when the two strands are pulled apart by a constant force. When
the force exceeds a critical threshold, a remarkable unzipping
transition occurs which is strongly influenced by randomness in the
base pair sequence. The DNA unzips via a series of discrete jumps
which allow it to reach successively deeper energy minima. Above the
threshold force, the dynamics of the unzipping force is related to
that of a particle diffusing in a random force field. Time
permitting, we will describe related problems involving bacterial
growth in an inhomogeneous medium with diffusion and convection and
the stalling out of detachable motor proteins, such as DNA and RNA
polymerase, while moving along linear
filaments with quenched
randomness.
y:
May 7th, 2002
Title:"Identifying
Importance of Amino Acids for Protein Folding"
By: Dr. Nikolay V. Dokholyan
Department Of Chemistry
and Chemical
Biology
Harvard University
ABSTRACT:
The concept of the protein transition state ensemble (TSE), a
collection of the conformations that have 50% probability to convert
rapidly to the folded state and 50% chance to rapidly unfold,
constitutes the basis of the modern interpretation of protein
engineering experiments. It has been conjectured that conformations
constituting the TSE in many proteins are the expanded and distorted
forms of the native
state built around a specific folding
nucleus. While this view is supported by a number of simplified
lattice model simulations, the TSE in structurally and dynamically
realistic folding simulations has not been seen. Here we report the
first direct observation and characterization of the TSE by
molecular dynamic folding
simulations of the C-Src SH3 domain, a
small protein that has been extensively studied experimentally. Our
analysis reveals a set of key interactions between residues,
conserved by evolution, that must be formed to enter the kinetic
basin of attraction of the native state.
y:
April 30th, 2002
Title:"Genomics
and Proteomics Analysis Using Time-of-Flight Mass
Spectrometry"
By: Norman Chiu
Department of
Chemistry
Northeastern University
ABSTRACT:
As the studies of various genomes and proteomes are intensified,
the development of new technology for improving the analysis of
nuclei acids and proteins has become more important than ever.
Currently, mass spectrometry is the most commonly used analytical
technique for both genomics and proteomics studies. In mass
spectroscopic measurements, a molecular sample is first ionized and
the ions are subsequently separated in a selected mass analyzer
according to their mass-to-charge ratios. Using the soft ionization
technique called matrix-assisted laser desorption/ionization (MALDI)
or electrospray ionization (ESI), the molecular integrity of nucleic
acids and proteins can be preserved. To separate these molecular
ions, the simplest way is to utilize the differences in their
mobilities within a time-of-flight mass analyzer. Mass accuracy of
<100ppm can be repeatedly achieved from different biological
samples using time-of-flight mass spectrometers that are
commercially available. In this seminar, the basic principle and the
latest development on time-of-flight mass spectrometry will be
discussed. In addition, selected applications of time-of-flight mass
spectrometry for the genomics and proteomics analysis will be
described.
y:
April 23d, 2002
Title:"From
crumpling to cell growth"
By: Dr. Arezki
Boudaoud
Department of Mathematics, MIT and
Laboratoire de
Physique Statistique,
Ecole Normale Superiour,
FRANCE
ABSTRACT:
I will discuss two problems related to the remarkable properties
of thin sheets. First, when a piece of paper is crumpled,
deformations are focused along lines (ridges) and points (cone
tips). We have studied experimentally and theoretically the
compression of a ridge. This model situation could give a mechanism
for small scales generation in crumpling. Second, cells having walls
can be considered as shells filled with a liquid under pressure.
Mechanical arguments lead to predictions for cell sizes which I have
tested with data from the biology literature.
y:
April 16th, 2002
Title:"Collective behavior in mixtures of molecular motors
and
microtubules"
By:Dr. Andreas
Hanke
Clarendon Laboratory
Oxford University
UK
ABSTRACT:
The cooperative action of polymers, proteins, and other
macromolecules together with their interaction with energy
providers, such as ATP, determines fundamental processes in living
organisms. One instance of such collective behavior is the assembly
of microtubules in the spindle apparatus of cells during mitosis,
driven by motor proteins of the kinesin family under consumption of
energy from ATP. Reconstituted experiments on mixtures of
microtubules and motors indeed exhibit an ordered phase of the
microtubules in terms of aster and vortex patterns. In this talk, I
will discuss recent attempts to explain these experimental results
by a dynamic field theory approach in terms of coupled Langevin
equations, giving rise to nonequilibrium physics of coupled, driven
systems.
y:
April 2nd, 2002
Title:"Sensitivity of Wave Field Evolution and Manifold
Stability in Chaotic Systems"
By: Prof.
Steve Tomosvic
University of Washington at Pullman and Physics
Department at Harvard University
ABSTRACT:
The sensitivity of a wave field's evolution to small
perturbations is of fundamental interest. For chaotic systems, there
are two distinct regimes of either exponential or Gaussian overlap
decay in time. We develop a semiclassical approach for understanding
both regimes and give a simple expression for the crossover time
between the regimes. The wave field's evolution is considerably more
stable than the exponential instability of chaotic trajectories
seems to suggest. The resolution of this paradox lies in the
collective behavior of the appropriate set of trajectories. Results
are given for the standard map.
y:
February 11th, 2002
Title:"Biochemical studies on
recombinant prion protein-nucleic acid
interaction"
By:
P.K. Nandi
Pathologie Infectieuse et Immunologie, Institut
National de la Recherche Agronomique, FranceBy:
ABSTRACT:
The fatal neurodegenerative prion disease is both genetic and
infectious and can inflict on humans and other animals. Unlike in
viruses and bacteria, where nucleic acids carry the infection, a
structural change in the a-helix rich normal cellular prion protein,
PrPC to its b-sheet rich, scrapie isoform, PrPSC has been considered
as an obligatory step of the occurrence and propagation of the prion
disease (C, normal cellular prion protein, Sc stands for scrapie,
the prion disease in sheep). PrPSC-amyloid as well as intermediate
oligomers are associated with the neuropathology of the prion
disease. The process of conversion to PrPSC form has been postulated
to require the binding of a still unidentified cofactor 'protein X'
to PrPC . Nucleic acid can induce structural change of recombinant
prion protein to its b-sheet rich form which results in
polymerization of the protein to amyloid. The protein in turn
induces stepwise association of nucleic acid molecules to condensed
ordered aggregates or nucleoprotein complex globules which
spontaneously dissociate. This has led to the demonstration of
functional properties of the nucleoprotein complex. Our results may
indicate that nucleic acid can be the much sought for cofactor for
the conversion of prion protein to amyloid related to the prion
disease.
February 5th, 2002
Title: "DNA
Topology "
By: Professor Maxim
Frank-Kamenetskii
Center for Advanced Biotechnology and
Department of Biomedical Engineering
Boston University
By:
ABSTRACT:
By the virtue of DNA chemical structure, its
termini can be easily locked with each other forming the circular
molecule. As a result, numerous topological states are inherent in
DNA. The DNA molecule can form knots. The two strands in closed
circular duplex DNA form links of a high order (high linking
numbers). Topological invariants of knots and links play very
important role in the field of DNA. DNA topology is crucial for DNA
functioning. Special enzymes, DNA topoisomerases, resolve the DNA
topological problems in the cell. Very recently, various artificial
DNA topological (and pseudotopological) nanostructures have been
elaborated. They include relatively short single-stranded DNA
circles assembled sequence specifically on single-stranded and
double-stranded target DNA. Padlock and earring (pseudo)topological
probes are most promising for DNA diagnostics.
January 29th, 2002
Title: "Gating of the Nicotinic Acetylcholine Receptor.
Applications to Protein Function and Drug Binding"
By: Dr. Michael Ziebell
Department of
Neurobiology, Harvard Medical School
220 Longwood Ave. , Boston,
MA 02115
ABSTRACT:
Understanding the role of molecular
motion in biological cells is essential to answering the larger
question of how living creatures exist. Proteins perform their many
functions through dynamic shifts of domains that expose active sites
of the molecule involved in catalysis or interactions. These domain
movements are most often triggered by the binding of a ligand, and
require energy. Structures of proteins are useful in understanding
how a protein functions, but this information is greatly enhanced by
data showing which domains shift as a part of the protein's
function.
In this study we examine the motion of a membrane bound
ion channel in response to binding a ligand. This protein, the
nicotinic acetylcholine receptor, is a component of nervous
stimulation of muscle and its structure and function have been
studied for many years. This receptor consists of five heterologous
subunits that span the plasma membrane of mucsle cells at the
neuromuscular junction. Upon binding ligands in the extracellular
domain, the channel opens, allowing the passage of cations out of
the cell. We wish to understand how ligand binding, which occurs
many angstroms away from the channel pore, triggers a change in
conformation leading to channel opening.
To understand this
effect, we use unique photo-activatable drugs that covalently attach
to to the receptor. We can build a model of the receptor in
different conformations (open, closed or desensitized) based on the
sensitivity of key amino to drug attachment. Molecular modeling,
together with experimental data may give us a step-by-step process
by which the acetylcholine receptor operates. This study is of
particular interest since other ligand gated channels such as GABA,
glycine and 5HT3 receptors, may be gated using similar
mechanisms.
January 22th, 2002
Title: "Fast computation based on spike
rate"
By:
Dr. Mark van Rossum
Dept. of Biology
and Center for Complex Systems, Brandeis University
Waltham, MA
02454
ABSTRACT:
One of the classic neural coding schemes is rate
coding. In rate coding the information is coded in the firing rates
of the cells. This idea is been based on the experimental
observation that presenting the preferred stimulus often leads to an
increase in the firing rate of a neuron. However, rate coding has
been criticized because given the typical firing rate (up to 100 Hz)
and given the Poisson-like variability in typical cortical spike
trains, substantial averaging time would be needed for an accurate
estimate of the signal. Experimental data, however, suggests there
is only very little time for such averaging, as humans can
categorize stimuli within 150 ms (Thorpe et al., 1996).
In this paper we show how firing
rate can be coded in a population of neurons. More precisely, we
study how activity propagates through a layered feed-forward network
with some 50 integrate-and-fire neurons per layer. All neurons are
primed with an independent noise current and a net excitatory
current. Time varying stimuli is rapidly transmitted through many
layers (10 layers within 50 ms, not taking axonal delays into
account), whereas the temporal shape of the stimulus is highly
conserved.
Next, we show how this mode of operation can be used
for motion detection. We build a Reichardt-type motion detector,
which calculates motion by cross correlating the image with a
translated, time-delayed version of the image (Reichardt, 1957).
Instead, of relying on detailed biophysics to perform such
calculation, we perform motion detection in a simple feed-forward
circuit.:
January 15th, 2002
Title:
"Fluctuating energy landscapes and enzymes, molecular motors, and
ion pumps"
By: Professor Dean
Astumian
Department of Physics and
Astronomy, University of Maine,
ABSTRACT:
Non-equilibrium Fluctuations, whether imposed externally or
driven by an energy releasing chemical reaction, can cause a protein
to cycle through several conformations. This cycling can drive a
process thermodynamically uphill even though any one conformation
considered independently catalyzes the process in the downhill
direction. The results apply equally to driving a biochemical
reaction away from equilibrium by an enzyme, to formation of an
osmotic gradient across a membrane by a molecular pump, or to motion
and generation of force by a molecular motor.
December 10th, 2001
Title: "Attractor model of working memory
in the neocortex: theory meets experiment"
By: Professor
Xiao-Jing Wang
Center for Complex Systems, Brandeis University
By:
ABSTRACT:
In this talk, I
will give a survey of experiments and theoretical work on cortical
networks that show attractor-type dynamics underlying short-term
memory. I will discuss cellular and synaptic mechanisms and
collective network dynamics that may underlie short-term memory. I
will also show how such networks can perform `cognitive
computations' such as perceptual decision making.
December 4th, 2001
Title: "Computing with Neural
Synchrony"
By: Dr. Paul
Tiesinga
Sloan-Swartz Center for Theoretical Neurobiology, The
Salk Institute, La Jolla California By:
ABSTRACT:
The neural response elicited in response to a
stimulus presentation is often the product of two stimulus
attributes: firing rate=f(x)g(y). Here g is the gain function that,
for instance, represents the effects of attention or stimulus power.
The neural substrate for this fundamental computation remains
elusive. Recent experiments show that when attention is shifted to
the receptive field of a neuron, the firing of the neuron may become
more synchronized with other similar units, as observed in
somatosensory cortex [Steinmetz et al, Nature 404,187 (2000)], or
with the local field potential at gamma frequencies, as reported for
extrastriate cortex [Fries et al, Science 291, 1560 (2001)]. Here I
show using model simulations and in vitro experiments how synchrony
may subserve attentional gain modulation. I find that (1) synchrony
in interneuron networks can be modulated independently from mean
firing rate; (2) the firing rate of a neuron is the product of the
synchrony and the mean of the drive it receives. Hence, attention
may modulate the response of a circuit and change its sensitivity to
stimuli by shifting the synchrony of local inhibitory neurons.
November 13th, 2001
Title: "Application of Statistical Physics
to Physiology: Scaling Features in Human Heartbeat Dynamics"
By: Dr. Plamen Ch. Ivanov
Center for
Polymer Studies, Physics Department, Boston University and Beth
Israel Deaconess Medical Center, Harvard Medical School
By:
ABSTRACT:
We explore the degree to which
concepts developed in statistical physics can be usefully applied to
physiological signals. We illustrate the problems related to
physiologic signal analysis with representative examples of human
heartbeat dynamics under healthy and pathologic conditions. We show
that intrinsic scale-invariant properties of the heartbeat
fluctuations can be revealed even when embedded in noisy,
nonstationary time series. Our analyses of long records (up to
100,000 beats) indicate that the fluctuations in the beat-to-beat
intervals exhibit: (i) long-range power-law anticorrelations; (ii)
follow a universal scaling form in their distributions which is
stable over a wide range of time scales; and (iii) are characterized
by a broad multifractal spectrum. These scaling features indicate
hierarchical self-similar organization in the heartbeat
fluctuations, which breaks down with disease. The observed fractal
properties can help elucidate key aspects of the mechanisms of
cardiac neuroautonomic regulation. We present a physiologically
motivated stochastic feedback mechanism to address the question of
how the heart rhythm spontaneously self-regulates.
November 6th, 2001
Title: "Is the micro-rheology of living
cells governed by a glass transition?"
By: Dr. B. Fabry
Harvard School of Public Health,
Physiology Program, Boston, MA 02115
ABSTRACT:
Current descriptions view cell mechanics as an
interaction of distinct elastic and viscous components expressing a
limited range of characteristic relaxation times, with elasticity
thought to be regulated through a sol-gel transition. We developed a
micro-rheometer based on magnetically twisted beads that were bound
to integrin-receptors to measure the mechanical properties of
isolated adherent cells (airway smooth muscle cells, neutrophils,
bronchial epithelial cells and alveolar macrophages) over
frequencies spanning 5 orders of magnitude. Elastic stresses
dominated at frequencies below 300 Hz, increased only weakly with
frequency and followed a power law. Frictional stresses were also
weakly dependent on frequency below 30 Hz but approached a viscous
limit at higher frequencies. Surprisingly, data for all cell types,
frequencies and interventions studied could be scaled onto universal
master curves. This scaling identifies these cells as soft glassy
materials existing close to a glass transition, with an effective
noise temperature, x, of about 1.2. These results contradict current
models in that 1) relaxation processes exhibited no intrinsic
time-scale, implying stress relaxation proportional to t^(1-x), and
2) frictional stresses seemed to reside within solid cytoskeletal
structures and did not correspond to a viscous friction. These
findings point to the hypothesis that cytoskeletal proteins regulate
cell mechanical properties mainly by modulating the effective noise
temperature.
October 30th, 2001
Title: "Microstructure evolution in
polycrystals"
By: Dr. Alexander
Lobkovsky
Physics Department and CIRCS, Northeastern University
ABSTRACT:
Most material properties are strongly influenced by
the structure on the microscopic length scales. I will review types
of microstructures observed in casting of metals and focus on the
crystalline grains. To predict the formation and evolution of the
crystal grain structure, it is essential to understand the way grain
boundaries move and interact with impurities. I will present a
summary of previous modeling efforts in that direction and focus on
the phase field method for capturing the physics of grain
boundaries.
October 23, 2001, 2001
Title:
Tuning DNA "Strings": Controlling the Speed (and Direction) of
Molecular Engines that Replicate DNA
By: Anita Goel
Department of Physics, Div. of
Health,Sciences and Technology (HST), Harvard University and MIT and
Harvard Medical School
ABSTRACT:
Recent single molecule experiments are elucidating
new information about the dynamics of motor enzymes that move along
polymer substrates,includingtheir sensitivity to external control
parameters such as mechanical tension on the template. Meanwhile,
X-ray crystallographers have taken high-resolution snapshots of the
intricate machinery of these molecular motors (DNA polymerases)
involved in the act of replication. Drawing upon both recent
structural and single molecule data, we discuss how mechanical
forces might couple into the chemical reaction of DNA replication.
Time permitting, we might speculate on some possible relevances for
biophysics and nanotechnology.
October 16th, 2001
Title: "How HIV nucleocapsid protein aids
the folding of nucleic acids"
By: Professor
Mark Williams
CIRCS and Physics Department, Northeastern
UniversityBy:
ABSTRACT:
When single DNA molecules are stretched beyond
their normal B-form contour length to forces of ~65 pN, they undergo
a cooperative overstretching transition, such that very little
additional force is required to extend the molecule to 1.7 times its
contour length. By using an optical tweezers instrument to measure
the transition force as a function of pH and temperature, we have
demonstrated that the overstretching transition is a transition from
the double-stranded helical form of DNA to its single-stranded form.
We have measured the effect of HIV-1 nucleocapsid protein (NC) on
this helix-coil transition. The NC protein is regarded as a nucleic
acid chaperone, since it catalyzes the folding of nucleic acids into
conformations containing the maximum number of base pairs. We show
that NC accomplishes its chaperone activity, which is essential for
HIV replication, by inducing electrostatic attraction between
nucleic acids and lowering the barrier to melting small sections of
helical DNA.
October 9th, 2001
Title: "Secrets of Alien Technology Revealed! or
Chirality Transformations Propagating on Bacterial Flagella"
By: Professor Greg Huber
Physics
Department, University of Massachusetts, Boston MA
By:
ABSTRACT:
Chemotaxis in many bacterial species is made
possible by the remarkable dynamics of their multiple, rotating,
helical flagella. They bundle and de-bundle as their rotary motors
episodically change rotational direction. When the flagella are
bundled, the bacterium moves linearly, but the dissolution of the
bundle leads to a tumbling event that effectively randomizes the
cell's orientation. The motor reversal that initiates the tumbling
not only torques the flagella oppositely, but also reverse the
chirality of the filament, turning a left-handed helix into a
right-handed helix. Hotani has performed careful experiments on
helical flagella in external flows and he observed that regions
within the filament periodically flip to the opposite chirality, and
that those domains propagate stably downstream. I'll present a
dynamical model for this phenomenon based on the existence of two
competing locally stable states of opposite chirality whose
interaction with the flow is through the torque they produce. The
model displays a number of the key features seen in the experiments.
Tuesday, April 17th 2001
Title: "Nanoscale Electrostatics in
Mitosis"
By: Professor L. John Gagliardi
Rutgers University,
Camden, New Jersey
ABSTRACT:
Primitive biological
cells had to divide with very little biology. This work simulates a
physicochemical mechanism, based upon nanoscale electrostatics,
which explains the anaphase A poleward motion of chromosomes. In the
cytoplasmic medium that exists in biological cells, electrostatic
fields are subject to strong attenuation by Debye screening, and
therefore decrease rapidly over a distance equal to several Debye
lengths. However, the existence of microtubules within cells changes
the situation completely. Microtubule dimer subunits are assumed to
be electric dipolar structures that can act as intermediaries which
extend the reach of the electrostatic interaction over cellular
distances. Experimental studies have shown that intracellular pH
rises to a peak at mitosis, and decreases through cytokinesis. This
result, in conjunction with the electronic dipole nature of
microtubule subunits and the Debye screened electrostatic force is
sufficient to explain and unify the basic events during mitosis and
cytokinesis: (1)assembly of asters, (2)motion of the asters to
poles, (3) poleward motion of chromosomes(anaphase A), (4)cell
elongation(anaphase B), and (5)cytokinesis. This paper will focus on
simulation of the dynamics of anaphase A motion based on this
comprehensive model. The physicochemical mechamisms utilized by
primitive cells could provide important clues regarding our
understanding of cell division in modern eukaryotic cells.
Wednesday, February
21th 2001
Title: "Electrical
Alternans and Cardiac Fibrillation"
By: Robert F. Gilmour
Jr.
Professor of Physiology, Department of Biomedical Sciences,
Cornell University Jo
ABSTRACT:
The leading cause of death in the US is
ventricular fibrillation(VF), a rapid and highly irregular heart
rhythm. Despite intensive study,the mechanism for VF is poorly
understood. It has been proposed that theonset of VF involves the
disintegration of a single spiral wave of excitation into many
self-perpetuating waves. Such a process requires that the slope of
the relationship between the duration of the cardiacelectrical
impulse and the interval between impulses (the restitutionrelation)
be > 1. The same theory anticipates that a single spiral wavewill
not disintegrate if the slope of the restitution relation is < 1.
Using a novel dynamical method we have shown that the slope of
therestitution relation normally is > 1 and that drugs that
reduce the slopeto < 1 suppress VF. A steeply sloped restitution
relation is associatedwith beat-to-beat alternation of cardiac
electrical properties (electricalalternans). Propagation of
alternans may not be uniform, resulting inconcordant (in-phase) and
discordant (out of phase) alternans acrossspatially distributed
systems. The dispersion of electrical propertiesthat accompany such
patterns of activation and recovery may facilitate theinitiation of
reentrant (spiral wave) excitation.
Tuesday, February 20th 2001
Title: "Nonlinear DNAmics:
Designer Gene Networks"
By: J.J.
Collins
University Professor, Professor of Biomedical Engineering,
Boston University
ABSTRACT:
Many fundamental cellular processes are governed by
genetic programswhich employ protein-DNA interactions in regulating
function. Owing to recent technological advances, it is now possible
to designsynthetic gene regulatory networks, and the stage is set
for thenotion of engineered cellular control at the DNA level.
Theoretically, the biochemistry of the feedback loops associated
withprotein-DNA interactions often leads to nonlinear equations, and
the tools of nonlinear analysis become invaluable. In this talk,
wedescribe how techniques from nonlinear dynamics and molecular
biologycan be utilized to model, design and construct synthetic
generegulatory networks. We present examples in which we integrate
the development of a theoretical model with the constructionof an
experimental system. We also discuss the implications ofsynthetic
gene regulatory networks for gene therapy,
biotechnology,biocomputing and nanotechnology.
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