A genetically encoded phosphorescent, electron dense probe for correlative light and electron microscopy
Ended Project Grant Awarded Last action
- Award ID
- R41GM148117
- Recipient
-
Photon Biosciences LLC UEI H4E3QZYNTHD1
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $598,450
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date
- Originally
- Place of performance
- Washington, USA
Award details come from USAspending.gov.
Description
- Abstract
- The overall goal of this project is to engineer a genetically encoded phosphorescent, electron dense probe for correlative light and electron microscopy, or clem, that allows a single genetically encoded tag to be imaged under both modalities, cryogenic light and electron microscopy. This would greatly aid in modeling cellular structures at sub-nanometer, pseudo-atomic resolution, leading to biomedical innovations dependent upon understanding 3-dimensional cellular structures at the atomic level. The last decade has witnessed a "resolution revolution" in cryo-electron microscopy (cryo-EM) due to preceding decades of technical advancement in microscope design, direct electron detecting cameras, sample preparation techniques and software DEVELOPMENT1. Combined, these advances have indeed revolutionized the field of structural biology. However, the revolution is incomplete. The ultimate goal of structural studies is to understand the function, mechanism and dynamics of macromolecules in vivo. While in vitro studies of isolated complexes represents a critical progress towards this goal, ideally they should be visualized at high resolution within the context of their native cellular environments. To this end, cryo-electron tomography allows three-dimensional visualization of cellular structures, albeit at lower resolution than single particle ANALYSIS2. In this technique a tilt series of the cell, or a slice through the cell, is taken under low dose conditions. The fourier transforms of the individual images are then taken to give the back projected image in reciprocal space, where the series of two-dimensional transforms are then assembled into a single three-dimensional transform of the cellular structure. The three- dimensional reciprocal space transform of the cell is then RE-projected back into real space to give a three- dimensional view of the cellular structure at low nanometer resolution. To enable proteins to be visualized at super-resolution within the context of other cellular proteins and organelles, we are developing a genetically expressible probe that works for both light microscopy and cryogenic electron tomography. This novel and innovative probe will enable cellular structures to be modeled sub-nanometer resolution, leading to biomedical innovations dependent upon understanding 3-dimensional cellular structures at the atomic level.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$0 | |
| Amendment | $1,079 | |
| Amendment | $1,079 | |
| Amendment | $298,146 | |
| Original award | $298,146 |
Quick answers
Who received award R41GM148117?
R41GM148117 was awarded to Photon Biosciences LLC by National Institute of General Medical Sciences (National Institutes of Health) on August 1, 2022.
How much is award R41GM148117 worth?
$598,450 has been obligated on R41GM148117.
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