Physiology and Biophysics


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 @ HSB T-625
Jun 6 @ 4:00 pm – 5:00 pm

Neurobiology of the World’s Most Dangerous Animal

Leslie B. Vosshall, Ph.D.

Robin Chemers Neustein Professor Head of the Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, NY

Seminar abstract:

My group is interested in the molecular neurobiology of mosquito host-seeking behavior. Female mosquitoes require a blood meal to complete egg development. In carrying out this innate behavior, mosquitoes spread dangerous infectious diseases such as malaria, dengue, Zika, chikungunya, and yellow fever. Humans attract mosquitoes via multiple sensory cues including emitted body odor, heat, and carbon dioxide in the breath. The mosquito perceives differences in these cues, both between and within species, to determine which animal or human to target for blood-feeding. We have developed CRISPR/Cas9 genome-editing in the Aedes aegypti mosquito with the goal of understand how sensory cues are integrated by the female mosquito to lead to host-seeking behavior. Some of the questions we are currently addressing are: Why are some people more attractive to mosquitoes than others? How do insect repellents work? How are multiple sensory cues integrated in the mosquito brain to elicit innate behaviors? How do female mosquitoes select a suitable body of water to lay their eggs? Recent advances from my group in analyzing the molecular biology of host-seeking behavior will be discussed. host: Stan Froehner