Physiology and Biophysics

Seminars

Mar
28
Thu
2019
PBIO seminar series: Darrin Brager @ T-639 H.S.B.
Mar 28 @ 9:30 am – 10:30 am

The ups and downs of HCN channels in Fragile X syndrome

Darrin H Brager

Senior Research Scientist, Lecturer Department of Neuroscience, Biology Instruction Office NOTE: location T-639
Apr
23
Tue
2019
PBIO seminar series: Trevor Lamb @ G-328 H.S.B.
Apr 23 @ 9:30 am – 10:30 am
Rod and cone phototransduction:  Molecular mechanism, quantitative model, and evolution of the genes Trevor Lamb Eccles Institute of Neuroscience, John Curtin School of Medical Research The Australian National University host: Peter Detwiler   Abstract: The first part of this presentation will outline our current understanding of the molecular basis of the phototransduction cascade in vertebrate rod and cone photoreceptors.  An overview will be given of the molecules that participate in activation, shut-off, and Ca-feedback regulation of the response to light.  Activation will be described in terms of the 2‑D diffusional encounters between molecules (rhodopsin, transducin, and the phosphodiesterase PDE6).  A recent discovery of considerable importance is that the PDE6 is only activated when it has two transducins bound; thus, the binding of a single transducin has negligible effect.  As a result, activation of the PDE6 is substantially immune to spontaneous thermal activation of transducin.  This new understanding has required the development of an updated quantitative model of phototransduction.  The revised model provides new insights into: (1) the nature of the single-photon event; (2) the existence of an additional delay in the onset phase of the rod response; and (3) the recovery of rods from bright flashes, and the nature of so-called ‘dominant time constants’ of recovery. The second part of the presentation will describe how the vertebrate phototransduction cascade evolved.  Around 600–700 million years ago, a simple chordate ancestor of ours possessed ciliary photoreceptor cells that probably used a single class of opsin that linked via a G‑protein cascade to cyclic nucleotide-gated ion channels, in a cascade bearing many similarities to that in present-day cones and rods.  As in the case of many other vertebrate features, an event (strictly, a pair of events) of monumental significance was the occurrence of two rounds of whole genome duplication (2R WGD), that led in principle to a quadruplication of every gene.  I will summarize analyses of the phylogeny (in extant species) of the genes for the proteins mediating phototransduction, and I will then describe analyses of gene synteny.  The combination of these approaches provides remarkable insights into the gene duplications (and losses) that occurred, prior to 2R WGD, during 2R WGD, and subsequently, that led to the emergence of distinct isoforms for rod and cone phototransduction proteins in present-day vertebrates.      
Apr
24
Wed
2019
2019 Hille Lecture – Bernardo Sabatini @ TBA
Apr 24 @ 11:30 am – 12:30 pm
Bernardo Sabatini (Harvard Medical School) time: 11:30Am location: T – 435       host: Stan Froehner
May
16
Thu
2019
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
May
23
Thu
2019
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.  
Jun
6
Thu
2019
2019 Crill Lecture – Leslie B. Vosshall @ HSB T-625
Jun 6 @ 4:00 pm – 5:00 pm
http://vosshall.rockefeller.edu/ host: Stan Froehner