Physiology and Biophysics


2018 Lamport Lecture – Richard Vallee @ HSB T-639
Sep 25 @ 4:00 pm – 5:00 pm
2018 Lamport Lecture

Cytoplasmic Dynein and Kinesins in Brain Development and Autophagy

Microtubule Motor Proteins Are Involved in a Wide Range of cellular activities.  Recent work in our lab has involved the role of the motor proteins in neuronal migration and neurogenesis in the developing brain.  We have worked out mechanisms by which cytoplasmic dynein, its regulators Nde1 and Ndel1, and LIS1  and the kinesin Kif1a contribute to these functions as well as brain developmental disease. We have also found a new role for the dynein adaptor protein RILP as a master regulator of mTOR-dependent autophagy in neurons. Richard Vallee Professor of Pathology & Cell Biology Columbia University time: 4:00pm location: HSB, T-639 host: Stanley C. Froehner
PBIO seminar series: Mohan Gupta @ G-328 H.S.B.
Oct 4 @ 9:30 am – 10:30 am
The role of microtubule-generated tension in accurate mitotic chromosome segregation Mohan ‘Moe’ Gupta, Ph.D. Assistant Professor Iowa State University Hosts: Linda Wordeman and Alex Paredez seminar abstract: To ensure genome stability in mitosis, the spindle assembly checkpoint (SAC) delays anaphase if sister chromosomes are not bound to microtubules from opposite spindle poles. Only in this configuration can dynamic microtubules produce tension across sister kinetochores. The interdependency between kinetochore-microtubule attachment and tension has proved challenging to elucidating the role(s) of tension at kinetochores. Thus, whether the SAC responds simply to kinetochore attachment status, or also to tension status remains obscure. Unlike higher eukaryotes, budding yeast kinetochores bind only one microtubule, simplifying the relationship between attachment and tension. To address the role of microtubule-generated tension in checkpoint signaling, we developed a Taxol-sensitive yeast model that allows tension to be reduced by microtubule stabilization in fully assembled spindles with attached kinetochores. Our results reveal that reducing tension on attached kinetochores delays anaphase onset. The tension-specific delay is transient relative to that imposed by kinetochores that are both unattached and tensionless. Furthermore, the mechanism requires only a subset of the core SAC proteins. Our results demonstrate that reduced tension generates a signal to delay anaphase that is temporally and mechanistically distinct from that characterized for unattached kinetochores.
PBIO seminar series: Ellen Lumpkin @ G-328 H.S.B.
Nov 8 @ 9:30 am – 10:30 am
Exciting touch: Synaptic mechanisms in mamalian touch receptor
Ellen Lumpkin, Ph.D.
Associate Professor of Somatosensory Biology in Physiology & Cellular Biophysics and Dermatology
Columbia University
host: John Tuthill
seminar abstract A rich variety of mechanosensitive cells trigger distinct skin sensations such as pressure, flutter and pain.  A growing body of research indicates that epithelial cells play a key role in sensation by activating or modulating peripheral neurons in healthy skin.  Dr. Lumpkin’s research aims to unveil how epithelial Merkel cells work in concert with the nervous system to generate different qualities of touch sensation.  To tackle this question, her group uses neurophysiology, quantitative neuroanatomy, intersectional mouse genetics and optogenetics.  Recently, they demonstrated that Merkel cells have dual roles in mechanosensation: they transduce sustained pressure, and amplify information transfer during dynamic touch, which encodes shapes and textures.  The seminar will ocus on the molecular signaling mechanisms through which Merkel cells excite sensory neurons.
PBIO seminar series: Daniel Denman @ G-328 H.S.B.
Nov 15 @ 9:30 am – 10:30 am
Correlated spike time variability, population coding, and synchrony in the early visual system.
Daniel Denman, PhD
Allen Institute
host: Adrienne Fairhall
Seminar abstract: In response to repeated presentation of the same stimulus, many visual neurons produce a variable number of spikes. This variability in spike count can be independent, correlated, or anti-correlated between pairs of neurons, and the implications of such correlations on sensory encoding have been extensively explored. In addition, spikes can also occur at variable times within the response (i.e., jitter, or spike time variability). While the magnitude of correlated spike count variability in spike count has been well-studied, the magnitude and sign of correlations in jitter, and any potential implications for visual coding, are not known. In this talk I will present measurements, using high-density electrophysiology (Neuropixels), of correlated jitter within small populations of 20-200 simultaneously recorded neurons across lateral geniculate nucleus and primary visual cortex. I will further discuss proposed mechanisms of correlated jitter and implications for potential and observed synchrony in visual cortical population responses.
PBIO seminar series: Luke Rice @ HSB G-328
Nov 29 @ 9:30 am – 10:30 am

Mechanism and regulation in microtubule dynamics

Luke Rice, Ph.D.
Associate Professor, Department of Biophysics, UT Southwestern Medical Center
host: Chip Asbury
Seminar abstract: Microtubules are dynamic polymers of αβ-tubulin that have essential roles in intracellular organization and chromosome segregation. The dynamic properties of MTs are central to their function, and they derive from the properties of individual tubulin subunits and their interactions within the MT lattice. Microtubule dynamics is a fascinating problem that tests our ability to integrate ‘one molecule at a time’ views of biochemistry and structure with lower-resolution measurements of collective behavior. My laboratory is focused on bridging this gap by discovering and quantifying the structural and molecular mechanisms that underlie microtubule dynamics and the action of regulatory factors. To provide a new way to study and perturb microtubule dynamics, my laboratory introduced methods for purifying recombinant αβ-tubulin on a scale that permits structural and biochemical studies.  Our work draws on structural, biochemical, and reconstitution studies as well as computational simulations. I will present recent work from my group that is uncovering the mechanisms of XMAP215-family polymerases and CLASP-family rescue factors. These are two cellular factors that regulate microtubule dynamics in different ways despite sharing a common domain organization. At the end of my talk I will presenting ongoing collaborative work in which we are applying interferometric scattering microscopy to observe the microtubule growth at the level of individual αβ-tubulins.
PBIO seminar series: EJ Chichilnisky @ G-328 H.S.B.
Dec 6 @ 9:30 am – 10:30 am
Toward a high-fidelity artificial retina
EJ Chichilnisky
John R. Adler Professor, Professor of Neurosurgery and of Ophthalmology and, by courtesy, of Electrical Engineering
host: Greg Horwitz
seminar abstract: Retinal prostheses represent an exciting development in science, engineering, and medicine – an opportunity to create devices that exploit our knowledge of neural circuitry in order to replace or even enhance visual function. However, although existing retinal prostheses demonstrate proof of principle in treating incurable blindness, they produce limited visual function. Some of the reasons for this can be understood based on the exquisitely precise and specific circuitry that mediates visual signaling in the retina. These considerations suggest that future devices may need to operate at single-cell, single-spike resolution in order to mediate naturalistic visual function. I will show large-scale multi-electrode recording and stimulation data from the primate retina indicating that, in many cases, such resolution is possible. I will also discuss cases in which it fails, and propose that we can substantially improve ariticial vision in such conditions by incorporating our knowledge of the visual system in bi-directional devices that adapt to the host neural circuity. Finally, I will discuss the potential implications for other neural interfaces of the future.
PBIO seminar series: Michael Long @ G-328 H.S.B.
Dec 13 @ 9:30 am – 10:30 am
seminar title: TBA Michael Long, PhD Associate Professor, Neuroscience and Physiology NYU, School of Medicine host: Adrienne Fairhall
PBIO seminar series: Carlos Portera-Cailliau @ G-328 H.S.B.
Feb 21 @ 9:30 am – 10:30 am
Dr. Carlos Portera-Cailliau, UCLA   Host: Andres Barria
PBIO seminar series: Burns C. Blaxall, Ph.D. @ G-328 H.S.B.
Mar 21 @ 9:30 am – 10:30 am
seminar title: TBA Burns C.Blaxall, PhD, FAHA, FACC, FAPS
Director of Translational Science, Heart Institute Director, Center for Translational Fibrosis Research Co-Director, Heart Institute Clinical Research Core & Biorepository
Cincinnati Children’s Hospital Medical Center Professor, UC Department of Pediatrics   host: Chris Liu
2019 Hille Lecture – Bernardo Sabatini @ TBA
Apr 24 all-day
time: TBD location: TBD Bernardo Sabatini (Harvard Medical School)     host: Stan Froehner
PBIO seminar series: Colleen Clancy @ G-328 H.S.B.
May 16 @ 9:30 am – 10:30 am
Colleen Clancy UC Davis   host: Sharona Gordon
PBIO seminar series: Rachel Martin @ G-328 H.S.B.
May 23 @ 9:30 am – 10:30 am
What can we learn about protein solubility and aggregation from a cold fish?
Rachel Martin
Professor Departments of Chemistry and Molecular Biology & Biochemistry UC Irvine
host: Sharona Gordon
seminar abstract: The βγ-crystallin fold that is ubiquitous in the structural proteins of the vertebrate eye lens is an ancient structural motif found in diverse organisms from all three domains of life. In organisms without eyes, e.g. archaea, bacteria, tunicates, and sponges, βγ-crystallins serve as calcium-binding proteins.  In vertebrates, they are primarily found in the eye lens, where they play an important role in controlling the refractive index gradient of this specialized tissue.  The ubiquitous βγ-crystallins of the vertebrate lens are believed to have descended from an ancestral single-domain Ca2+-binding crystallin by a process that included gene duplication resulting in two copies of the double Greek key domain per chain, as well as selection for high refractive index. Because the lens has negligible protein turnover, the crystallins must remain stable and soluble for the lifetime of the organism despite their extremely high concentrations. In particular, we are interested in the resistance to phase separation of the cold-adapted crystallins of the Antarctic toothfish, Dissostichus mawsoni. The eye lens of D. mawsoni is evolutionarily adapted to function in the permanently sub-freezing waters of the Southern Ocean.  This is in contrast to temperate and tropical fishes, and endothermic mammals, the lenses of which undergo liquid-liquid phase separation at low temperatures.  Mammalian lenses phase separate at temperatures between 10 °C and 20 °C – well above the Antarctic’s sub-zero marine environment.  The ability of the toothfish lens to maintain transparency in this frigid environment is particularly remarkable given that fish lenses have a high concentration of constituent proteins ≥1000 mg * mL-1). Recent work in my group focuses on testing the hypothesis that γ-crystallin isoform heterogeneity coupled with cold selective evolutionary pressures contribute to the clarity of the toothfish lens.  We have measured the thermal stabilities and phase diagrams of seven key γ-crystallin lens proteins, and we are able to control the onset of liquid-liquid phase separation by introducing a small number of surface mutations. The implications of our findings with respect to the roles of frustration, ionic interactions, and protein flexibility liquid-liquid phase separation will be discussed.  
2019 Crill Lecture – Leslie B. Vosshall @ TBA
Jun 6 – Jun 5 all-day host: Stan Froehner