| NSF Org: |
MCB Division of Molecular and Cellular Biosciences |
| Recipient: |
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| Initial Amendment Date: | June 4, 2012 |
| Latest Amendment Date: | September 1, 2015 |
| Award Number: | 1149728 |
| Award Instrument: | Continuing Grant |
| Program Manager: |
Larry Halverson
MCB Division of Molecular and Cellular Biosciences BIO Directorate for Biological Sciences |
| Start Date: | June 1, 2012 |
| End Date: | May 31, 2017 (Estimated) |
| Total Intended Award Amount: | $1,150,810.00 |
| Total Awarded Amount to Date: | $1,150,810.00 |
| Funds Obligated to Date: |
FY 2015 = $431,731.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
615 W 131ST ST NEW YORK NY US 10027-7922 (212)854-6851 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
1212 Amsterdam Ave New York NY US 10027-7003 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): |
Cross-BIO Activities, MATHEMATICAL BIOLOGY, MSPA-INTERDISCIPLINARY, Systems and Synthetic Biology |
| Primary Program Source: |
01001516DB NSF RESEARCH & RELATED ACTIVIT |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
Intellectual Merit. Signaling networks are the information processing devices of cells and organisms. These drive complex processes such as the development of an entire human being from a single cell and protecting the body in a coordinated response to a pathogen. The immune system presents a unique opportunity for studying development in mammals. White blood cells undergo differentiation and proliferation, a never-ending process throughout the life of the organism. The goal of this research is to present a global, systems view of the immune system, its function and its development. The approach is based on a new revolutionary technology, Mass-Cytometry, which enables us to observe cellular signaling and development at unprecedented resolution and detail. This empowers the exploration of development in a brand new way, unraveling the mystery of how we are made from just a single cell.
Broader Impacts. Biological research is paved with novel technologies that lead to new opportunities, new challenges, and most importantly new discoveries. Elucidating general principles for molecular signal processing and development have great utility across a host of fundamental challenges in modern biology. This is an exciting era, during which interdisciplinary research can really make an impact on biology. To make such impact requires scientists trained in both quantitative and biological sciences. A key part of this project is to develop ways to distill complex science to a broader community, including science expo for K-8 and specialized systems biology training at the undergraduate and graduate levels. The modeling and visualization tools developed in this project are ideal for presenting the complexity of biological systems in a more tangible and concrete manner for students and are ideal training and outreach resources. The synergistic combination of technology and computation will have a transformative influence on broad topics across all of biology.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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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.
Rapidly evolving single cell technologies are transforming biology allowing researchers to query biological questions at unprecedented resolution. The NSF funding has enabled us to advance and utilize these technologies to gain fundamental insights into signaling as a means of cellular response, deepen our understanding of cell fate decisions and comprehensive characterization of heterogeneity in AML, a cancer of the blood cells. During the lifetime of the award, we have published 10 peer-reviewed high impact manuscripts in world leading journals such as Cell, Science and Nature Biotechnology.
Intellectual merit of the award
Single cell data is inherently noisy and very complex in nature. As part of our research, we have developed computational tools and methods such as viSNE, Biscuit and Phenograph which form a key part of the visualization and data analysis tool set widely used by researchers for single cell data analysis with viSNE being virtually synonymous with single cell data visualization. Our tools have produced results that are highly accurate, robust and reproducible in a wide array of applications.
Understanding how organisms develop from single cells and more generally cellular differentiation and how cells assimilate information from their environments to mount effective response are some of the most fundamental questions in biology. We have used single cell data to shed light on these key processes through our research funded by NSF. Our methods DREMI and DREVI to functionally and quantitatively to characterize intracellular signaling networks demonstrate how immune cells fine tune their responses and mount effective response. Our trajectory detection algorithms, Wanderlust, Cycler and Wishbone transformed the way cellular differentiation is computationally studied by establishing a novel framework for modeling differentiation. This cutting-edge research has significantly advanced our understanding of cell fate decisions and regulatory processes driving immune cell differentiation.
Broader impact of the award
The research carried out was highly inter-disciplinary and collaborative in nature bringing together scientists with expertise in computer science, mathematics, molecular biology and biochemistry. NSF funding has enabled us to cross-train graduate students and post docs across multiple disciplines, equipping a new breed of computational biologists to tackle key problems in biology. We have also provided research opportunities for undergraduate students who have benefited from their experiences in the lab to enter graduate programs in some of the best universities.
The insights gained from our research along with the development of computational methods for understanding and analyzing single cell data was one of the drivers for establishment of the Human Cell Atlas project. Human Cell Atlas project is a global, multi-institute, transformative project that aims to build comprehensive reference maps for all cell types in the human body providing a basis for understanding human health and treating disease.
Last Modified: 09/13/2017
Modified by: Dana Peer
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