seminars & bulletins


10:30am (unless otherwise noted)
Refreshments follow the seminar


PBIO Special Events

Health Sciences Bulletin

Seminar Series archives


Tuesday - October 02, 2012 
Special lecture: 2012 Lamport Lecture

W. Jonathan Lederer
Director & Professor, Center for Biomedical Engineering and Technology, Professor of Physiology, University of Maryland, School of Medicine
"New signaling pathway in muscle: X-ROS"

4:00pm, D-209 HSB

X-ROS signaling is a novel redox signaling pathway that links mechanical stress to changes in [Ca2+]i. This pathway is activated rapidly and locally within a muscle cell under physiological conditions, but can also contribute to Ca2+-dependent arrhythmia in heart and to the dystrophic phenotype in heart and skeletal muscle 1, 2. Upon physiologic cellular stretch, microtubules serve as mechanotransducers to activate NADPH oxidase 2 (NOX2) in the transverse tubules and sarcolemmal membranes to produce reactive oxygen species (ROS). In heart, the ROS acts locally to activate ryanodine receptor Ca2+ release channels in the junctional sarcoplasmic reticulum, increasing the Ca2+ spark rate and "tuning" excitation-contraction coupling. In skeletal muscle, where Ca2+ sparks are not normally observed, the X-ROS signaling process is muted. However in muscular dystrophies, such as Duchenne Muscular Dystrophy and dysferlinopathy, X-ROS signaling operates at a high level and contributes to myopathy. Importantly, in skeletal muscle Ca2+ permeable stretch-activated channels are activated by X-ROS and contribute to the cellular pathology. In brief, X-ROS provides an exciting new mechanism for the mechanical control of redox and Ca2+ signaling in cardiac and skeletal muscle.

  1. 1. Khairallah RJ, Shi G, Sbrana F, Prosser BL, Borroto C, Mazaitis MJ, Hoffman EP, Mahurkar A, Sachs F, Sun Y, Chen YW, Raiteri R, Lederer WJ, Dorsey SG, Ward CW. Microtubules underlie dysfunction in duchenne muscular dystrophy. Sci Signal. 2012;5:ra56
  2. 2. Prosser BL, Ward CW, Lederer WJ. X-ros signaling: Rapid mechano-chemo transduction in heart. Science. 2011;333:1440-1445

Host: Stan Froehner

October 11, 2012 

Gautam Awatramani
University of Victoria
"Past, present and future: How the retina anticipates the future to “see” the present"

Slow neural processing is an inherent property that the brain must overcome in order to perceive the world in real time. For example, in the visual system, images are transduced by light detecting cells in the eye (photoreceptors) extremely slowly and the brain receives signals only ~1/10th of a second after the image first falls on the retina. Why is this problematic? For reading this sentence, it probably didn’t matter that the brain registered images with a slight delay. But consider what happens during tennis, when Nadal serves. While the image of the ball hits Federer’s eye almost instantaneously, it is processed for a tenth of a second before the ball can be perceived. During this time, the ball has continued to move, so that by the time Federer perceive the ball, it is actually in a different location. Since Nadal sends the ball rocketing at ~180 km/hour, neural delays of 100 ms would cause the ball to appear as if it lagged 5m behind its actual location, which would make it difficult for Federer to face his opponent’s serve. But we know Federer has no problem returning serve (on his good days!), meaning that his brain can somehow compensate for delays. How does the brain do this? I will present our latest results in which for the first time, we show that a few specialized motion coding cells in the retina (known as directionally selective ganglion cells), have a surprising ability to anticipate future motion and allow the retina to ‘see’ in real time. I will present evidence that a novel interaction between “chemical” and “electrical” synapses is used to perform this remarkable computation.

Host: Fred Rieke

Monday - October 15, 2012 

Dan Needleman
Assistant Professor of Applied Physics; Assistant Professor of Molecular and Cellular Biology, Harvard
"Physical Aspects of Spindle Assembly"

3:30 pm

The spindle is a complex assembly of microtubules, motors, and other associated proteins, which segregate chromosomes during cell division.
In metaphase, the spindle exists in a steady-state with a constant flux of molecules and energy continuously modifying and maintaining its architecture. While the self-organization of systems of microtubules and motors have been investigated using theory and experiments, there have been few attempts to test if the proposed theories can be used to understand the dynamics and structure of complex biological systems in vivo. Here we use polarized light microscopy, 3D time-lapse spinning disk confocal microscopy, single molecule imaging, second harmonic generation microscopy, and mechanical measurements to test the validity of continuum models of metaphase spindles. Our results show that a simple continuum model can quantitatively explain spindle structure and dynamics, demonstrate that rigorous physical theories can be used to quantitatively describe complex subcellular systems, and provides a framework for understanding the structure of the spindle and its response to physical and molecular perturbations.

Host: Chip Asbury
Co-hosting Department: Sackler Program, and Seattle Mitosis Club

November 01, 2012 

Adam Hebb
Assistant Professor of Neurological Surgery, University of Washington Neurological Surgery Dept.
"Searching for Synchrony between Cortical and Subcortical Oscillations in Parkinson's Disease"

Host: Eb Fetz

January 24, 2013 

Anthony Leonardo
Janelia Farm
"Guidance laws and neural circuits underlying prey capture in dragonflies"

Host: Adrienne Fairhall

January 31, 2013 

Zhuan Zhou
Professor and Senior Investigator, Peking University
"Calcium independent but voltage dependent secretion (ciVDS) in primary sensory neurons"

Host: Bertil Hille

March 28, 2013 

Richard Kitsis
Professor & Director Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine
"Unifying Cell Death Programs"

Host: Chris Liu

April 04, 2013 

David Warshaw
Professor and Chair of Molecular Physiology & Biophysics, University of Vermont
"Molecular Mechanics of Cardiac Myosin Binding Protein-C: Why Is It There?"

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament associated protein that is composed of 11 Ig- and fibronectin-like domains (C0-C10). Through its N-terminal domain interactions with actin and/or myosin, cMyBP-C is believed to regulate cardiac contractility. This regulation can be modulated by phosphorylation of 4 serines in the motif linker between C1-C2. At the molecular level:
1) How does cMyBP-C affect actomyosin force and motion generation when it is confined to discrete locations on the thick filament (i.e. C-zones)?
2) Which N-terminal domains of cMyBP-C are involved?
3) How does motif phosphorylation modulate cMyBP-C function and does phosphorylation alter the mechanical properties of the motif?
To address these questions, we used a combination of single molecule biophysical techniques (i.e. TIRFM, laser trap, AFM), in vitro protein expression, proteomics, and transgenic mouse models. Using native mouse cardiac thick filaments, which retain cMyBP-C’s spatial distribution on the thick filament, we characterized the motion of single actin filaments being propelled along the thick filament. These studies demonstrate that cMyBP-C slows actin filament velocity only within the C-zone and that the N-terminal 29kDa domain is responsible for this slowing. Using bacterially-expressed N-terminal fragments in the motility and laser trap assays, we further localized the N-terminal interaction domain to at least C1 and the first 17 amino acids of the motif. In native thick filaments, motif phosphorylation reduced the inhibitory effect of cMyBP-C on actin filament velocity in a graded manner, i.e., in proportion to the extent of overall motif phosphorylation. This was confirmed in the laser trap assay by characterizing the force:velocity relationship from a small ensemble of monomeric myosin (~16 heads) in the presence of C0-C3 fragments with 1 or more serines replaced by aspartic acids as phosphomimetics. We speculated that motif phosphorylation alters the structural stability of the motif, thus affecting the cMyBP-C’s binding affinity for actin and/or myosin. In fact, using atomic force microscopy, the motif in fully phosphorylated C0-C3 fragments adopts a more stable structure in comparison to the motif in unphosphorylated C0-C3, which is freely extensible. Therefore, cMyBP-C is a potent regulator of cardiac contractility through its N-terminal interactions with actomyosin, with itself being modulated through by the extent of motif phosphorylation.

Host: Sharona Gordon
Co-hosting Department: Sacker Scholars Program

April 11, 2013 

Valentin Dragoi
Assistant Professor, University of Texas, Houston
"Population coding in visual cortical networks"

Host: Adrienne Fairhall

April 15, 2013 

Frances Ashcroft - Hille Lecture
GlaxoSmithKline Royal Society Research Professor , Oxford
"ATP-sensitive potassium channels: their role in neonatal diabetes and neurological complications "

3:30, A-420 Hogness

Host: Stan Froehner

April 18, 2013 

Greg Horwitz
Assistant Professor , University of Washington
"Exploring V1 with adaptive stimulus selection and optogenetics"

Host: Jane Sullivan

May 09, 2013 

Elizabeth M. Quinlan
Associate Professor, University of Maryland
"Obligatory role for NARP-dependent recruitment of inhibition in critical period plasticity"

Host: Andres Barria

May 30, 2013 

Jim Berg, Ph.D.
Allen Brain Institute
"Establishing an electrophysiology pipeline to characterize cortical neuron subtypes"

Host: Rieke

June 27, 2013 

Jack Waters
Associate Investigator , Allen Institute for Brain Science
"Neocortical pyramidal neurons: dendritic excitability and modulation by nicotinic acetylcholine receptors"

Host: Jane Sullivan