Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In preliminary studies, we have shown that both HD negative and HD positive human embryonic stem cells are capable of differentiation to neuronal cells which express cytoskeletal structural proteins such as ?-III-tubulin and MAP2ab and glial cells which express the characteristic protein GFAP. Measurements of stem cell derived neurons indicate that their axons and dendrites are typically 1-2?m in diameter, making them ideal targets for TXM imaging. We hypothesise that soft X-ray tomography imaging using the carbon K-edge in combination with immune-gold labelling of HTT fibrillar aggregates, organelles (such as mitochondria), and the cytoskeleton will be a powerful imaging approach for elucidating subtle structural changes within the neurons related to mutant HHT and may shed new light into the molecular the mechanisms that lead to neurodegeneration.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR019664-07
Application #
8362744
Study Section
Special Emphasis Panel (ZRG1-BST-K (40))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
7
Fiscal Year
2011
Total Cost
$19,596
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

McHugh, Emma; Batinovic, Steven; Hanssen, Eric et al. (2015) A repeat sequence domain of the ring-exported protein-1 of Plasmodium falciparum controls export machinery architecture and virulence protein trafficking. Mol Microbiol 98:1101-14
Do, Myan; Isaacson, Samuel A; McDermott, Gerry et al. (2015) Imaging and characterizing cells using tomography. Arch Biochem Biophys 581:111-21
Le Gros, Mark A; McDermott, Gerry; Cinquin, Bertrand P et al. (2014) Biological soft X-ray tomography on beamline 2.1 at the Advanced Light Source. J Synchrotron Radiat 21:1370-7
Smith, Elizabeth A; Cinquin, Bertrand P; Do, Myan et al. (2014) Correlative cryogenic tomography of cells using light and soft x-rays. Ultramicroscopy 143:33-40
Dasgupta, Sabyasachi; Auth, Thorsten; Gov, Nir S et al. (2014) Membrane-wrapping contributions to malaria parasite invasion of the human erythrocyte. Biophys J 107:43-54
Hanssen, Eric; Dekiwadia, Chaitali; Riglar, David T et al. (2013) Electron tomography of Plasmodium falciparum merozoites reveals core cellular events that underpin erythrocyte invasion. Cell Microbiol 15:1457-72
Smith, Elizabeth A; Cinquin, Bertrand P; McDermott, Gerry et al. (2013) Correlative microscopy methods that maximize specimen fidelity and data completeness, and improve molecular localization capabilities. J Struct Biol 184:12-20
Parkinson, Dilworth Y; Epperly, Lindsay R; McDermott, Gerry et al. (2013) Nanoimaging cells using soft X-ray tomography. Methods Mol Biol 950:457-81
Isaacson, Samuel A; Larabell, Carolyn A; Le Gros, Mark A et al. (2013) The influence of spatial variation in chromatin density determined by X-ray tomograms on the time to find DNA binding sites. Bull Math Biol 75:2093-117
McDermott, Gerry; Le Gros, Mark A; Larabell, Carolyn A (2012) Visualizing cell architecture and molecular location using soft x-ray tomography and correlated cryo-light microscopy. Annu Rev Phys Chem 63:225-39

Showing the most recent 10 out of 29 publications