The applicant has a strong quantitative background in physics, optics, and computers, and has strong interest in research. Further training in biomedical research methods, in particular cell biology and hypothesis-driven science, would enable a broader range of interdisciplinary problems to be attacked, and lead to his successful development as an independent biomedical investigator. The training environment includes the University of Maine, where the P.I. is building a new laboratory and the Institute for Molecular Biophysics. Due to a recent growth in biophysics, the interdisciplinary links between the Institute and the Jackson Laboratory, and the acquisition of the first 4Pi microscope in the U.S., there are many opportunities for highly relevant biomedical research collaborations, symposia, workshops, and team grant writing at the University. Collaborative visits to the NIH, where the mentor runs a well-established laboratory, will provide excellent opportunities for research training, interaction with biomedical experts, and access to equipment. ? ? The research plan focuses on the problem of viral infection, which causes considerable mortality. Infection by influenza depends on membrane fusion, which is mediated through the protein HA by a cholesterol- and sphingolipid-sensitive mechanism that likely involves microscopic membrane clusters called rafts. However, the size, shape, mechanism, and dynamics of such domains are currently disputed. This project will use novel, relatively noninvasive fluorescence spectroscopic methods to test whether domains form by partitioning or by direct interaction between HA and lipids. The project will also determine whether the domains are static or dynamic on millisecond and microsecond timescales, and test whether the cytoskeleton mediates domain size or dynamics in cells. Because information about raft dynamics is in shortage, the proposed methods have an unusual advantage. Results will be used to attempt to better understand how influenza virus is able to congregate its own proteins for budding and entry (fusion). ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
1K25AI065459-01
Application #
6955627
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Lacourciere, Karen A
Project Start
2005-09-01
Project End
2010-07-30
Budget Start
2005-09-01
Budget End
2006-07-30
Support Year
1
Fiscal Year
2005
Total Cost
$124,042
Indirect Cost
Name
University of Maine Orono
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
186875787
City
Orono
State
ME
Country
United States
Zip Code
04469
Mlodzianoski, Michael J; Curthoys, Nikki M; Gunewardene, Mudalige S et al. (2016) Super-Resolution Imaging of Molecular Emission Spectra and Single Molecule Spectral Fluctuations. PLoS One 11:e0147506
Gabor, Kristin A; Kim, Dahan; Kim, Carol H et al. (2015) Nanoscale imaging of caveolin-1 membrane domains in vivo. PLoS One 10:e0117225
Deschout, Hendrik; Cella Zanacchi, Francesca; Mlodzianoski, Michael et al. (2014) Precisely and accurately localizing single emitters in fluorescence microscopy. Nat Methods 11:253-66
Avilov, Sergiy; Berardozzi, Romain; Gunewardene, Mudalige S et al. (2014) In cellulo evaluation of phototransformation quantum yields in fluorescent proteins used as markers for single-molecule localization microscopy. PLoS One 9:e98362
Gabor, Kristin A; Stevens, Chad R; Pietraszewski, Matthew J et al. (2013) Super resolution microscopy reveals that caveolin-1 is required for spatial organization of CRFB1 and subsequent antiviral signaling in zebrafish. PLoS One 8:e68759
Gudheti, Manasa V; Curthoys, Nikki M; Gould, Travis J et al. (2013) Actin mediates the nanoscale membrane organization of the clustered membrane protein influenza hemagglutinin. Biophys J 104:2182-92
Kim, Dahan; Curthoys, Nikki M; Parent, Matthew T et al. (2013) Bleed-through correction for rendering and correlation analysis in multi-colour localization microscopy. J Opt 15:
Curthoys, Nikki M; Mlodzianoski, Michael J; Kim, Dahan et al. (2013) Simultaneous multicolor imaging of biological structures with fluorescence photoactivation localization microscopy. J Vis Exp :e50680
Gould, Travis J; Hess, Samuel T; Bewersdorf, Joerg (2012) Optical nanoscopy: from acquisition to analysis. Annu Rev Biomed Eng 14:231-54
Gunewardene, Mudalige S; Subach, Fedor V; Gould, Travis J et al. (2011) Superresolution imaging of multiple fluorescent proteins with highly overlapping emission spectra in living cells. Biophys J 101:1522-8

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