| NSF Org: |
MCB Division of Molecular and Cellular Biosciences |
| Recipient: |
|
| Initial Amendment Date: | September 29, 2010 |
| Latest Amendment Date: | September 29, 2010 |
| Award Number: | 1052733 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Gregory W. Warr
MCB Division of Molecular and Cellular Biosciences BIO Directorate for Biological Sciences |
| Start Date: | October 1, 2010 |
| End Date: | June 30, 2015 (Estimated) |
| Total Intended Award Amount: | $281,986.00 |
| Total Awarded Amount to Date: | $281,986.00 |
| Funds Obligated to Date: |
|
| History of Investigator: |
|
| Recipient Sponsored Research Office: |
1 SCIENCE PARK BOSTON MA US 02114-1099 (617)589-0118 |
| Sponsor Congressional District: |
|
| Primary Place of Performance: |
1 SCIENCE PARK BOSTON MA US 02114-1099 |
| Primary Place of
Performance Congressional District: |
|
| Unique Entity Identifier (UEI): |
|
| Parent UEI: |
|
| NSF Program(s): |
Cellular Dynamics and Function, Cross-BIO Activities |
| Primary Program Source: |
|
| Program Reference Code(s): |
|
| Program Element Code(s): |
|
| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
1052623
Winter, Jessica O. (lead PI)
Collaborative Research: QSTORM: Switchable Quantum Dots and Adaptive Optics for Super-Resolution Imaging
Imaging is one of the most important tools in biology. However, observing biological structures and processes in living cells at a resolution below the diffraction limit of light microscopy (~200 nm) remains extremely challenging. Recently, several super-resolution techniques have been introduced to improve the resolution of optical fluorescence, with reported static and dynamic resolutions reaching ~20 nm and ~60 nm, respectively. However, these techniques have yet to be translated to the live cell because of difficulties caused by limitations of fluorescent probes and optical aberrations and light scattering in tissues. Thus researchers must extrapolate information from images of fixed specimens to the living state. This project proposes a new super-resolution imaging technology: QSTORM, which combines user-controlled, switchable quantum dots (QDs) with specialized computer-based algorithms (STORM) and adaptive optics to enhance images. QSTORM will, for the first time, enable imaging in living cells with a resolution superior or comparable to other super-resolution techniques. QSTORM will be evaluated in two models systems: the structure and function of muscle myofilaments in zebrafish and the intracellular transport of vesicles in fruit fly neurons. Normal muscle function depends on the highly organized multi-scale architecture of muscle tissue. QSTORM will enable simultaneous imaging of functioning myofilaments, sarcomeres, and whole muscle cells within the same sample. Similarly, axonal transport of cargo by vesicles is critical to the survival and function of neuronal cells. QSTORM will permit observation of the movements of individual vesicles and the mapping of the underlying cytoskeletal structures that enable this transport. Additionally, the QSTORM team will collaborate with the Museum of Science in Boston to share the results of this research broadly through science education programs, museum demonstrations, and Web-based multimedia projects.
Intellectual merit. If fully successful, QSTORM will harness the superior imaging capabilities of quantum dots and adaptive optics for live cell imaging at a super-resolution of less than 50 nm. QSTORM will transform imaging of biological processes, particularly those involving the cytoskeleton and motor proteins. In the models to be studied, QSTORM will permit three-dimensional high resolution imaging of intact live muscle without the destructive processing required for transmission electron microscopy (TEM), thus potentially leading to new hypotheses of how muscle proteins such as actin, myosin, and associated proteins interact. Similarly, QSTORM will permit, for the first time, imaging the movements of neuronal vesicles over complete transport cycles along the entire length of the axon at single nanometer resolution, thus potentially transforming current understanding of the fundamental molecular
mechanisms of transport and its regulation.
Broader impacts. QSTORM will contribute a powerful new microscopy tool to the scientific community. Not only will this research produce extraordinary images that offer visual insight into fundamental biological processes, but also the broader dissemination of results and educational activities will widely advance subcellular biological research and training. Researchers, students, educators, and public audiences will benefit from the potentially extraordinary visualizations produced by QSTORM. This research will be incorporated into graduate and undergraduate courses in a wide-range of disciplines. Collaboration with the Museum of Science will provide broadly accessible and nationally disseminated educational materials. The proposed QSTORM Web site will present these extraordinary images as part of a lively multimedia story of high-risk, interdisciplinary scientific and technical collaboration in pursuit of a grand challenge.
PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
The major goal of this five-institution collaborative research project is to develop a new imaging technology for probing real-time molecular-scale activities inside living cells. The plan is to enhance stochastic optical reconstruction microscopy (STORM) super-resolution imaging techniques by incorporating the use of biologically-compatible, user-controlled, switchable quantum dots (QDs) and adaptive optics (AO). Goals also include education and training of undergraduate and graduate students, and outreach to broader audiences about this publicly supported research initiative. Museum of Science (MOS) PI Carol Lynn Alpert leads the QSTORM team's research coordination, communication, and public outreach efforts.
Major Outcomes: 2010 - 2015
1. QSTORM.ORG Collaborative Research Website & Education Portal
The team website, developed and maintained by the Alpert group at MOS, sent a new precedent for collaborative research team communications. It served as this multi-institutional team's main organ for sharing data, tracking progress, monitoring meetings and events, education, and context. 100% of QSTORM participants (n=15) reported in the post-project student survey that the website contributed to their "sense of being a member of the larger overall QSTORM collaborative effort," and that they used the website "to learn about what the other research teams were doing." 87% used it "to check back on past efforts and findings." The website contains 85 pages of explanatory content, images, experimental data, timelines, tutorials and animations, videos, faculty and student bios, meeting notes, and more than 700 blog posts and comments from contributors, including PIs, the post-docs, graduate students, and several undergraduate students. Public viewership of the QSTORM website has been increasing yearly since its launch in 2011. The site has logged over 80,000 page views and - even in its legacy format - continues to attract new and returning visitors, for whom it serves as an portal into collaborative research in biological imaging.
2. Public Presentation "Making Molecular Movies with QSTORM"
PI C.L. Alpert and MOS Program Manager K. Thate developed a 20 minute public presentation to engage public audiences in QSTORM collaborative quest, that has set a new standard for current science and technology presentations at MOS and elsewhere. Developed through an iterative R&D process informed by IRB-approved visitor survey methods, the presentation is remarkably successful with a wide variety of adult and family audiences, even though it includes advanced content in molecular biology, optics, and chemical engineering. 97% of visitors surveyed (n=142) reported the presentation was interesting (73% rated it as “Very Interesting”); 86% found it easy to understand; and 76% reported that they were likely to visit the website. The presentation has recently been updated so that it could continue being presented in a legacy format. It has been delivered at MOS 182 times and experienced by more than 6500 people. It has also been presented at COSI Columbus, the Carnegie Science Center in Pittsburgh, and at the 2014 Fall MRS Meeting. The videotaped version is posted on qstorm.org and on YouTube.
3. QSTORM Public Media
The MOS group also produced 3 podcasts with the researchers. These went out to 5,000 MOS iTunes subscribers plus 1200 NanoNerds subscribers: Ge Yang - Aug 2012 “QSTORM: Looking inside Nerve Cells," Jessica Winter - July 2014 “Scale Up for NanoBioTech with Jessica Winter," and Peter Kner - Aug 2014 “M...
Please report errors in award information by writing to: awardsearch@nsf.gov.
