Physiology and Biophysics

Seminars

Jan
19
Thu
2017
PBIO Seminar Series: Polina Lishko @ HSB G-328
Jan 19 @ 9:30 am – 10:30 am

An ion channel on steroids: the unconventional pathway of calcium regulation by endogenous cannabinoids

Polina Lishko, PhD Assistant Professor of Cell and Developmental Biology Department of Molecular and Cell Biology UC Berkeley Host: Sharona Gordon Ion channels control sperm activity by regulating intracellular levels of calcium, which stimulates cell motility and fertility. Steroid hormone progesterone produced by an ovulated egg promotes the entry of calcium through sperm channel CatSper- an event so central for fertilization that men lacking these channels are infertile. We have demonstrated that human CatSper is associated with a membrane progesterone receptor, which makes human spermatozoa controlled by the female reproductive cycle. The identity of this receptor has been recently revealed to be serine hydrolase ABHD2 that degrades endogenous CatSper inhibitor 2-arachidonoylglycerol upon progesterone exposure. ABHD2 is ubiquitously expressed, and the pathway we have discovered in spermatozoa, is likely a universal pathway that defines membrane steroid signaling in other tissues.
Mar
20
Mon
2017
PBIO seminar – Manu Ben-Johny, Ph.D. @ HSB G-328
Mar 20 @ 9:30 am – 10:30 am
Feedback control of sodium and calcium channels – from shared molecular underpinnings to synthetic modulation. Manu Ben-Johny, Ph.D. Department of Bioengineering Johns Hopkins University   Abstract: The voltage-gated sodium (NaV) and calcium (CaV) channels constitutes two major ion-channel superfamilies with custom molecular attributes that enable a multitude of unique biological functions. For example, the NaV channels support brisk spatial propagation of action potentials while the CaV channels couple excitability to contraction, secretion, and transcription. Yet, one similarity of these channels is their homologous carboxy-tail, a segment that is a hotspot for diverse cardiac arrhythmogenic and neurological disorders. If this region were to support like-functions, deep mechanistic insights could be gleaned from the joint investigation of these channels, and shared principles derived for approaching related channelopathic diseases. For CaV channels, dynamic interactions between their tail domains and calmodulin elaborate rapid and recognizably similar forms of Ca2+-feedback regulation. However, for NaV channels, Ca2+ effects have long-appeared to be subtle and variable with divergent purported mechanisms, dimming prospects for unification. Here, using quantitative Ca2+-photouncaging and single-channel recordings, we show that these differences are only apparent and that Ca2+ regulatory function and mechanism are fundamentally conserved across the two channel families. Despite this high similarity and dependence on a modular structural element, we demonstrate how cells employ distinct auxiliary proteins to selectively switch feedback control of NaV versus CaV channels and vice versa. Overall, these results help substantiate the persistence of an ancient Ca2+-regulatory design across channel superfamilies, unravel the sophisticated mechanisms by which cytosolic proteins tune cellular excitability and calcium signaling, and reveal new strategies to engineer the molecular function of ion channels. host: Stan Froehner
Mar
23
Thu
2017
PBIO seminar – Yao Chen, Ph.D. @ HSB G-328
Mar 23 @ 9:30 am – 10:30 am
Unexpected lessons on neuromodulator action from imaging molecular signals Yao Chen, Ph.D. Department of Neurobiology Harvard Medical School   Abstract: Neuromodulators such as acetylcholine and dopamine have profound effects on neural circuits and behavior. However, how neuromodulator-induced molecular signals influence behavior represents an outstanding gap in our understanding of neuromodulator action. In order to go beyond the identity to the action of molecular signals, we need to know the subcellular and cellular specificity as well as temporal dynamics of neuromodulator-induced molecular signals. One of the major challenges to uncover these features is the lack of methods to dynamically monitor the molecular signals induced by G protein-coupled receptor (GPCR) activation with high spatial resolution. A critical intracellular integrator of GPCRs is protein kinase A (PKA). PKA activity is stimulated by Gαs-coupled and inhibited by Gαi-coupled neuromodulator receptors, and this push-pull relationship can bidirectionally modulate synaptic function as well as transcription. In order to monitor PKA activity in the brain, we modified a PKA activity sensor and developed optical approaches that enable quantitative analysis of endogenous GPCR signaling in brain tissue with two-photon fluorescence lifetime imaging microscopy. Using this reporter, we have found that, contrary to the canonical model of GPCR signaling, endogenous Gαq-coupled neuromodulator receptors elevate phosphorylation by PKA in the mouse hippocampus. I will present this discovery that highlights PKA as a central integrator of three major types of GPCR signals. Furthermore, I will share ongoing work suggesting that the same neuromodulator input (e.g. acetylcholine) can produce different PKA signals depending on the context of cellular physiology and animal experience. Finally, I will outline my future directions that aim to examine the spatial location, temporal dynamics and context dependence of neuromodulator-induced molecular signals, and how these features of molecular signaling contribute to cellular physiology and animal behavior.       host: Stan Froehner
Mar
30
Thu
2017
PBIO seminar – Arnold Hayer, Ph.D. @ HSB G-328
Mar 30 @ 9:30 am – 10:30 am

Collective endothelial cell migration – cadherin fingers lead the way

Arnold L. Hayer, Ph.D. Department of Chemical and Systems Biology Stanford University Abstract: The development and maintenance of the vasculature requires collective cell movement, during which neighboring cells coordinate the polarity of their migration machineries. We addressed the unresolved question of how polarity signals are transmitted from one cell to another across symmetrical cadherin junctions, using an in vitro model of collective endothelial cell migration. We found that collectively migrating endothelial cells have polarized VE-cadherin-rich membrane protrusions, ‘cadherin fingers’, which leading cells extend from their rear and follower cells engulf at their front. In follower cells, engulfment of cadherin fingers occurs along with the formation of a lamellipodia-like zone with low actomyosin contractility, and requires VE-cadherin/catenin complexes and Arp2/3-driven actin polymerization. Lateral accumulation of cadherin fingers in follower cells precedes turning, and increased actomyosin contractility can initiate cadherin finger extension as well as engulfment by a neighboring cell, to promote follower behavior. Cadherin fingers create positively curved membrane surfaces only in the front of follower cells, which selectively recruit and polarize curvature sensing regulatory proteins. Thus, engulfment of cadherin fingers at the cell front converts symmetric cadherin junctions into polarized structures that support collective cell guidance. Further, I will discuss our recent identification of a BAR domain and RhoGAP protein, which is required both for coordinated endothelial cell movement and vascular sprouting in vitro, and therefore establishes an intriguing mechanistic link between the asymmetric cadherin finger structure and RhoGTPase signaling. host: Stan Froehner
Apr
6
Thu
2017
2017 Hille Lecture – Thomas Schwarz @ Foege Auditorium
Apr 6 @ 4:00 pm – 5:00 pm
Moving and Removing Axonal Mitochondria Thomas L. Schwarz, PhD Professor Neurology F.M. Kirby Center for Neurobiology Children’s Hospital, Boston and Dept. of Neurobiology, Harvard Medical School Time: 4:00PM Location: Foege Auditorium, GNOM S060 seminar abstract: Mitochondria are dynamic organelles.  In every cell they move and undergo fission and fusion.  Their distribution and associations with the cytoskeleton change in response to many signals, including the mitotic cell cycle.  In addition, because neurons look like no other cell in the organism, with axons of up to a meter in humans, mitochondrial motility is particularly crucial to the survival of the neuron. The neuron also needs to clear away damaged mitochondria efficiently wherever in the cell they may arise.  Not surprisingly then, defects in the transport machinery of neurons and in their mechanisms for removing damaged mitochondria have been linked to several neurodegenerative diseases, including ALS and Parkinson’s disease.  This talk will present the evidence for a motor/adaptor complex that is responsible for and regulates the movement of mitochondria and will discuss how that movement is regulated by the cell cycle, Ca++, and glucose.  We will look at the operation of two proteins PINK1 and Parkin that are mutated in forms of Parkinson’s disease and examine how these proteins operate in axons to clear away damaged mitochondria that might otherwise compromise the health of the cell.  Particularly in the case of mitophagy, we will consider the special challenges posed for neurons by their extended geometry and the difficulty of having a PINK1-dependent pathway operating far from the soma.  
Apr
13
Thu
2017
PBIO seminar – Rui Chang @ HSB G-328
Apr 13 @ 9:30 am – 10:30 am
From body to brain: control of autonomic physiology by the sensory vagus nerve Rui Chang, Ph.D. Department of Cell Biology Harvard Medical School Seminar abstract: Cardiac, respiratory, and other autonomic functions are precisely controlled by the nervous system, yet many autonomic reflexes remain poorly characterized at a molecular and cellular level. The sensory vagus nerve is a major conduit between body and brain, and is critical for many autonomic physiology. Using a genetic approach, we molecularly deconstructed the vagus nerve, and successfully identified neuron populations that are critically involved in respiratory physiology and digestive functions. We further elucidated the molecular mechanism for lung inflation-mediated apnea. Together, these findings lay the groundwork for a molecular dissection of respiratory and gastrointestinal physiology.
Apr
20
Thu
2017
PBIO seminar – Claudia Moreno @ HSB G-328
Apr 20 @ 9:30 am – 10:30 am

Couple, amplify, fire!

Coupling of L-type calcium channels and excitability

L-type CaV1.2 and CaV1.3 calcium channels are key players in the generation and regulation of electrical activity in different cell types, including neurons and myocytes. In the pacemaker cells of the heart, the spike of the action potential that initiates each heartbeat depends entirely on the entry of calcium through these channels. Recently, we discovered a novel cooperative gating mechanism, on both CaV1.2 and CaV1.3 channels, which facilitates calcium entry and modulates the excitability of ventricular cardiomyocytes and neurons. We found that these channels establish a calcium-dependent physical interaction via their c-termini, which results in an increase in their open probability. Our more recent project aims to answer two new questions: Do CaV1.2 and CaV1.3 channel undergo functional coupling in the pacemaking cells of the heart? And, if so, is this coupling modulated by physiological stimuli? Our new results point to a mechanism by which beta-adrenergic signaling increases the coupling of CaV1.2 channels in the pacemaker cells. These exciting results add to our understanding on how the sympathetic nervous system increases heart rate.   Claudia Moreno, Ph.D. Department of Physiology and Membrane Biology School of Medicine University of California, Davis host: Stan Froehner
Apr
27
Thu
2017
PBIO Seminar Series: Chris Liu @ HSB G-328
Apr 27 @ 9:30 am – 10:30 am
“Molecular Signaling Mechanisms of Cardiac Remodeling and Heart Failure” Chris Liu University of Washington Dept of Physiology & Biophysics   host: Stan Froehner
May
4
Thu
2017
PBIO Seminar Series: Dr. Felix Viana @ HSB G-328
May 4 @ 9:30 am – 10:30 am
“Molecular physiology of cold-activated TRP channels” Dr. Félix Viana Tenured Investigator of the Spanish Council for Scientific Research (CSIS) Instituto de Neurociencias de Alicante  Institute of Neurosciences, Alicante (Spain) Visiting Scholar in the Department of Biological Structure, UW Transient receptor potential (TRP) channels are a family of cationic channels with important roles in many aspects of sensory physiology, from vision to taste. Several of these channels are highly sensitive to temperature and have been shown to play critical roles in thermoreception, thermoregulation and pain. I will provide an overview of our work with two cold-activated channels, TRPA1 and TRPM8, highlighting their differential function in cold transduction, thermoregulation and nociception, and some newly discovered pathophysiological roles outside the nervous system. host: Bertil Hille
May
11
Thu
2017
PBIO Seminar Series: Daniel Polley @ HSB G-328
May 11 @ 9:30 am – 10:30 am
Rebooting sensory processing after afferent loss: probing the capabilities and limitations of adult cortical plasticity  Daniel Polley, PhD Harvard Medical School Massachusetts Eye and Ear Infirmary host: Ed Rubel abstract: Following a near-complete loss of auditory nerve fibers that convey signals from the cochlea to the brain, all evidence of central sound processing grinds to a halt. Over the ensuing weeks, neurons at higher stages of central auditory processing increase the gain on the small fraction of remaining inputs and restore perceptual awareness and normative rate coding, even when markers of brainstem processing indicate complete deafness. I will describe our efforts to understand the mechanisms and limitations of this “cortical amplifier” that supports a partial compensatory plasticity. The second half of the talk will address whether further gains of function might be possible through auditory training tasks that activate cholinergic neurons in the basal forebrain. In particular, we are motivated to discover ways to ‘de-noise’ cortical representations of stimuli embedded in high levels of background noise. These experiments describe a multiplexed encoding of auditory stimuli and behavioral reinforcement signals in cholinergic neurons of Nucleus Basalis that project to the auditory cortex. We ask how these neurons are activated during auditory learning, first through simple auditory fear conditioning and ultimately through complex audiomotor tasks that generate high levels of sensory prediction errors. We conclude by showing how training on closed-loop audiomotor behavioral tasks can broadly enhance cortical and perceptual processing of faint sounds near the noise floor both in unit recordings from the mouse auditory cortex and through measurements of speech processing in elderly human subjects with profound hearing loss.
Jun
15
Thu
2017
PBIO Seminar Series: Jean Claude Beique @ HSB G-328
Jun 15 @ 9:30 am – 10:30 am
Jun
20
Tue
2017
2017 Crill Lecture – William Bialek @ D-209 HSB
Jun 20 @ 4:00 pm – 5:00 pm
Thinking about a thousand neurons William Bialek John Archibald Wheeler/Battelle Professor in Physics Princeton University
Sep
21
Thu
2017
PBIO Seminar Series: Andrei Smertenko @ HSB G-328
Sep 21 @ 9:30 am – 10:30 am

How plants conquer the space: the cell’s flying plates

Plant cytokinesis is orchestrated by a specialized structure, the phragmoplast. The phragmoplast first occurred in representatives of Charophyte algae and then became the main division apparatus in land plants.  Major cellular activities, including cytoskeletal dynamics, vesicle trafficking, membrane assembly, and cell wall biosynthesis, cooperate in the phragmoplast under the guidance of a complex signaling network. My research focuses on the self-organization processes that govern phragmoplast functions. I will give a general overview of plant cytokinesis, and present our recent data on the gamma-tubulin independent microtubule nucleation by the plant-specific protein MACERATOR and a conserved member of TPX2 protein family.

Andrei Smertenko, Ph.D. Assistant Professor, Molecular Plant Sciences Washington State University host: Linda Wordeman
Sep
28
Thu
2017
PBIO Seminar Series: [no speaker scheduled] @ HSB G-328
Sep 28 @ 9:30 am – 10:30 am
Oct
5
Thu
2017
PBIO Seminar Series: [no speaker scheduled] @ HSB G-328
Oct 5 @ 9:30 am – 10:30 am
Oct
12
Thu
2017
PBIO Seminar Series: Liangyi Chen @ HSB G-328
Oct 12 @ 9:30 am – 10:30 am

High spatiotemporal resolution, three-dimension fluorescence imaging of biological samples in vivo

Dr. Liangyi Chen Professor Laboratory of Cell Secretion and Metabolism Institute of Molecular Medicine, Peking University, Beijing, China Host: Bertil Hille Abstract: I will give two stories. (i) One story describes unpublished ultrasensitive Hessian structured illumination microscopy that enables ultrafast and long-term super-resolution (SR) live-cell imaging. At a photon dose one order less than point-scanning microscopy, Hessian-SIM has achieved 88-nm and 188-Hz spatial-temporal resolution for live cells imaging and lasted thousands of images without artifacts. Operating at 1 Hz, Hessian-SIM enables hour-long, time-lapse SR imaging with mitigatable photobleaching, highlighting the possibility of achieving SR imaging with commonly used fluorophores for an unlimited period of time. (ii) The second story is our recent Nature Methods paper, our invention of the fast high-resolution miniature two-photon microscope for brain imaging in freely-behaving mice at the single-spine level. With a headpiece weighing 2.15 g and a new type of hollow-core photonic crystal fiber to deliver 920-nm femtosecond laser pulses, the mini-microscope is capable of imaging commonly used biosensors at high spatiotemporal resolution (0.64 μm laterally and 3.35 μm axially, 40 Hz at 256 × 256 pixels). It compares favorably with benchtop two-photon microscopy and miniature wide-field fluorescence microscopy in the structural and functional imaging of Thy1-GFP- or GCaMP6f-labeled neurons. Further, we demonstrate its unique application and robustness with hour-long recording of neuronal activities down to the level of spines in mice experiencing vigorous body and head movements or engaging in social interaction.
Oct
19
Thu
2017
PBIO Seminar Series: [no speaker scheduled] @ HSB G-328
Oct 19 @ 9:30 am – 10:30 am
Oct
26
Thu
2017
PBIO Seminar Series: Brian Kalmbach @ HSB G-328
Oct 26 @ 9:30 am – 10:30 am
“Of Mice and Men: Intrinsic Membrane Properties of Human Cortical Pyramidal Neurons” Brian Kalmbach, Ph.D. Allen Institute for Brain Science host: Nikolai Dembrow
Nov
2
Thu
2017
2017 Lamport Lecture – Gilles Laurent @ T-739 HSB
Nov 2 @ 4:00 pm – 5:00 pm

Evolution and brain computation

I will introduce our work towards identifying principles of brain function and computation, focused on using comparative approaches and exploiting unusual model systems (reptiles, cephalopods) to study sleep, texture perception and cerebral cortex evolution. Gilles Laurent, PhD, DVM Director Max Planck Institute for Brain Research http://www.brain.mpg.de/home/   4:00 PM Location: T-739, HSB   host: Stan Froehner
Nov
9
Thu
2017
PBIO Seminar Series: [no speaker scheduled] @ HSB G-328
Nov 9 @ 9:30 am – 10:30 am
Nov
16
Thu
2017
PBIO Seminar Series: [no speaker scheduled] @ HSB G-328
Nov 16 @ 9:30 am – 10:30 am
Nov
30
Thu
2017
PBIO Seminar Series: [no speaker scheduled] @ HSB G-328
Nov 30 @ 9:30 am – 10:30 am
Dec
7
Thu
2017
PBIO Seminar Series: Nikolai Dembrow @ HSB G-328
Dec 7 @ 9:30 am – 10:30 am
Title: TBA Nikolai Dembrow, PhD host: Stan Froehner
Dec
14
Thu
2017
PBIO Seminar Series: [no speaker scheduled] @ HSB G-328
Dec 14 @ 9:30 am – 10:30 am
Dec
21
Thu
2017
PBIO Seminar Series: [no speaker scheduled] @ HSB G-328
Dec 21 @ 9:30 am – 10:30 am
Jan
4
Thu
2018
PBIO Seminar Series: save for CompNeuroSearch @ HSB G-328
Jan 4 @ 9:30 am – 10:30 am
Save for Computational Neuroscience Search
Jan
9
Tue
2018
PBIO Seminar: Rishidev Chaudhuri @ HSB G-328
Jan 9 @ 9:30 am – 10:30 am
“Cognitive manifolds and their dynamics across states and areas” Rishidev Chaudhuri, PhD. Center for Learning & Memory The University of Texas at Austin Host: Stanley C. Froehner
Jan
16
Tue
2018
PBIO Seminar: Ashok Litwin-Kumar, PhD @ HSB G-328
Jan 16 @ 9:30 am – 10:30 am
“Randomness and structure in neural representations for learning” Ashok Litwin-Kumar, PhD Center for Theoretical Neuroscience Columbia University Host: Stanley C. Froehner
Jan
25
Thu
2018
Canceled – Seminar: Amy Bastian, PhD @ HSB G-328
Jan 25 @ 9:30 am – 10:30 am

Canceled

Dr. Bastian’s seminar will be rescheduled for a later date.

   

Learning and Relearning Movement

Human motor learning depends on a suite of brain mechanisms that are driven by different signals and operate on timescales ranging from minutes to years. Understanding these processes requires identifying how new movement patterns are normally acquired, retained, and generalized, as well as the effects of distinct brain lesions. The lecture focuses on normal and abnormal motor learning and how we can use this information to improve rehabilitation for individuals with neurological damage Amy Bastian, Ph.D. Professor of Neuroscience Johns Hopkins University   Host: John Tuthill  
Feb
1
Thu
2018
PBIO Seminar: Julijana Gjorgieva, PhD @ HSB G-328
Feb 1 @ 9:30 am – 10:30 am
Organizing principles in developing networks and sensory populations Julijana Gjorgieva, PhD Research Group Leader, Max Planck Institute for Brain Research Assistant Professor for Computational Neuroscience, Technical University of Munich Host: Stanley C. Froehner