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SUMMARY:Acoustic Small-molecule Biosensors for Ultrasound Imaging
LOCATION:Virtual Seminar
TZID:America/Denver
DTSTART:20210426T163000
UID:2026-04-23-21-13-29@natsci.colostate.edu
DTSTAMP:20260423T211329
Description:Research Seminar\n\nThe visualization of molecular-level proces
 ses within living organisms should be considered a cornerstone of next-gen
 eration medicine. To that end\, ultrasound can noninvasively image deep ti
 ssue with high spatiotemporal resolution but is lacking in molecular-level
  biosensors analogously available to other imaging modalities1. Gas vesicl
 e (GV) protein nanostructures have recently been proposed as ultrasound co
 ntrast agents that are easily detectable in the context of living organism
 s. To date\, GV characteristics have been engineered at the constituent pr
 otein level to achieve cell targeting\, surface charge\, fluorescence\, cl
 onability\, and differential acoustics and collapse pressures2–4. More r
 ecently\, GVs have been adapted as ultrasound biosensors that “light up
  in the presence of protease activity5. While these advancements demonst
 rate the potential utility of GVs in a clinical setting\, the toolset of u
 ltrasound imaging can be further enhanced through the detection of small m
 olecules. Herein is proposed three independent protein engineering aims fo
 cused on the central objective of generating acoustic small-molecule biose
 nsors. In Aim 1\, conditionally stable ligand-binding protein domains will
  be fused as chimeras to GV constituent protein gas vesicle protein C (Gvp
 C). Aim 2 will install ligand-induced conformational switch domains within
  the sequence of GvpC through randomized transposon insertion. Aim 3 will 
 discover mechanisms of ligand-responsive behavior through a library-based 
 directed evolution strategy involving cellular buoyancy.\n\n&nbsp\;\n\n(1)
  Maresca\, D.\; Lakshmanan\, A.\; Abedi\, M.\; Bar-Zion\, A.\; Farhadi\, A
 .\; Lu\, G. J.\; Szablowski\, J. O.\; Wu\, D.\; Yoo\, S.\; Shapiro\, M. G.
  Biomolecular Ultrasound and Sonogenetics. Annu. Rev. Chem. Biomol. Eng. 2
 018\, 9 (1)\, 229–252. https://doi.org/10.1146/annurev-chembioeng-060817
 -084034.\n\n(2) Lakshmanan\, A.\; Farhadi\, A.\; Nety\, S. P.\; Lee-Gossel
 in\, A.\; Bourdeau\, R. W.\; Maresca\, D.\; Shapiro\, M. G. Molecular Engi
 neering of Acoustic Protein Nanostructures. ACS Nano 2016\, 10 (8)\, 7314
 7322. https://doi.org/10.1021/acsnano.6b03364.\n\n(3) Bourdeau\, R. W.\;
  Lee-Gosselin\, A.\; Lakshmanan\, A.\; Farhadi\, A.\; Kumar\, S. R.\; Nety
 \, S. P.\; Shapiro\, M. G. Acoustic Reporter Genes for Noninvasive Imaging
  of Microorganisms in Mammalian Hosts. Nature 2018\, 553 (7686)\, 86–90.
  https://doi.org/10.1038/nature25021.\n\n(4) Lakshmanan\, A.\; Lu\, G. J.\
 ; Farhadi\, A.\; Nety\, S. P.\; Kunth\, M.\; Lee-Gosselin\, A.\; Maresca\,
  D.\; Bourdeau\, R. W.\; Yin\, M.\; Yan\, J.\; Witte\, C.\; Malounda\, D.\
 ; Foster\, F. S.\; Schröder\, L.\; Shapiro\, M. G. Preparation of Biogeni
 c Gas Vesicle Nanostructures for Use as Contrast Agents for Ultrasound and
  MRI. Nat Protoc 2017\, 12 (10)\, 2050–2080. https://doi.org/10.1038/npr
 ot.2017.081.\n\n(5) Lakshmanan\, A.\; Jin\, Z.\; Nety\, S. P.\; Sawyer\, D
 . P.\; Lee-Gosselin\, A.\; Malounda\, D.\; Swift\, M. B.\; Maresca\, D.\; 
 Shapiro\, M. G. Acoustic Biosensors for Ultrasound Imaging of Enzyme Activ
 ity. Nat Chem Biol 2020\, 16 (9)\, 988–996. https://doi.org/10.1038/s415
 89-020-0591-0.\n\nJoin Zoom Meeting\nMeeting ID: 991 5275 1265\nPasscode: 
 1872 4:30 pm
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