
NSF Org: |
MCB Division of Molecular and Cellular Biosciences |
Recipient: |
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Initial Amendment Date: | December 21, 2010 |
Latest Amendment Date: | February 19, 2015 |
Award Number: | 1051344 |
Award Instrument: | Continuing Grant |
Program Manager: |
Ranajeet Ghose
MCB Division of Molecular and Cellular Biosciences BIO Directorate for Biological Sciences |
Start Date: | January 1, 2011 |
End Date: | June 30, 2016 (Estimated) |
Total Intended Award Amount: | $300,000.00 |
Total Awarded Amount to Date: | $500,000.00 |
Funds Obligated to Date: |
FY 2012 = $50,000.00 FY 2013 = $50,000.00 FY 2014 = $50,000.00 FY 2015 = $50,000.00 |
History of Investigator: |
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Recipient Sponsored Research Office: |
55 LAKE AVE N WORCESTER MA US 01655-0002 (508)856-2119 |
Sponsor Congressional District: |
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Primary Place of Performance: |
55 LAKE AVE N WORCESTER MA US 01655-0002 |
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): |
Molecular Biophysics, PHYSICS OF LIVING SYSTEMS, Cross-BIO Activities |
Primary Program Source: |
01001516DB NSF RESEARCH & RELATED ACTIVIT 01001112DB NSF RESEARCH & RELATED ACTIVIT 01001415DB NSF RESEARCH & RELATED ACTIVIT 01001213DB 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
The goal of the Protein Folding and Dynamics Research Coordination Network (RCN), which is jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences and the Physics of Living Systems Program in the Division of Physics in the Mathematical and Physical Sciences Directorate, is to promote interactions that would transform the understanding of the mechanism by which the amino acid sequence of a protein directs its rapid and efficient folding to the native, functional conformation. To achieve this goal, a group of experienced investigators with complementary expertise in both experimental and computational/theoretical biophysics have established a consortium whose intentions are to integrate their combined efforts on the folding reactions of a select set of targets. Repeated cycles of computer simulations by theorists and experimental validation by bench scientists on a set of common targets are expected to significantly accelerate progress on the solution to the folding problem and transform the way one thinks about the relationship between the sequence, folding and structure of proteins. A solution to the protein folding problem would resolve one of the remaining fundamental challenges in biology, provide essential insights for the design of innovative industrial catalysts and substantially improve the yields of protein products in the biotechnology arena. The networking activities of the RCN will primarily flow through the frequent interactions among the members of each project team via the internet. Network activities will also include two meetings each year, one involving the core participants and the second involving members of their research groups. A dynamic and inclusive culture for the consortium will be promoted by invitations to other investigators and their students who are willing to share their complementary expertise in collaborations with core members of the project teams. These invited investigators are also expected to bring new protein targets to the consortium to expand the repertoire of motifs under study.
The RCN will support a new paradigm for solving complex problems in biology. This paradigm will take the form of concerted efforts from multiple labs with complementary expertise in experimental and theoretical/computational science to solve the folding problem. It is anticipated that success in this endeavor will inspire the formation of new consortia to solve other complex problems in biology. The RCN will also recruit a new generation of scientists from a broad range of disciplines to develop new approaches towards the solution of the protein folding problem. By recasting the protein folding problem in terms of the inherent physical properties of the folding reaction, the PI expects to attract the participation of young physicists, engineers, computer scientists, chemists and others who will bring their unique skills and perspectives towards its solution. These young scientists will also benefit from participating in collaborative research efforts and, perhaps, will seek similar opportunities as they build their own careers. It is expected that success in this project will have numerous societal benefits, including the elimination of the toxic solvents and wastes emanating from many industrial processes, the design of new biodegradable materials with remarkable properties and the training of the next generation of scientists.
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.
Goals of our Research Coordination Network program
Science has become a very interdisciplinary enterprise, with teams of investigators working on complex problems from a variety of perspectives. Their complementary expertise enables substantial progress on problems that are beyond the reach of any individual scientist. Recognizing the advantages of collective action, the principal objective of the Research Coordination Network: Protein Folding Consortium (RCN:PFC), funded by the National Science Foundation, was to provide a novel platform for establishing and nurturing collaborations and training between experimentalist, theorists and computational biologists. Our consortium originally focused on the mechanism by which unfolded proteins efficiently and rapidly attain their native functional conformations. Recently, we expanded our ambitions to the broader field of protein dynamics relevant to folding in vivo, function, intrinsically disordered proteins, macromolecular machines and evolution. The consortium also provided a novel training and mentoring platform for younger scientists in the labs of their sponsors. To achieve our objectives, the PFC supported two annual meetings, one with the principal investigators (PIs) and another with the PIs and their students and postdoctoral fellows, and a website. In many ways, the consortium acted as a virtual institute focused on the protein folding landscape and its many implications for the evolution of biological function.
Intellectual Merit
As described above, the goal of the PFC is to transform the way that we think about the protein folding problem and protein dynamics, in general, by creating a consortium of experimentalists, theorists and computational biologists whose collective efforts exceed the progress attainable by individual labs. For example, advances in high performance computing combined with novel sampling methods and the application of microfluidic mixing experiments now make it possible for simulations and experiments to study protein folding and dynamics on the microsecond time scale. Three of the consortium members brought their respective skills to bear on the folding of a small protein that initially misfolds in the microsecond time range. Other members have partnered to explore orthogonal experimental and computational approaches toward denaturing another small protein, while still others are probing the behavior of sequences that do not spontaneously fold to well-defined structures as is the norm for many, many proteins. Inquiries into the evolution of protein sequences over geologic time reveal the fundamental role of stability in dictating the sequence space sampled. The RCN has catalyzed 60 collaborations between its 30 members and resulted in almost 40 joint publications in its 5 years of existence.
Broader Impact
The broader impact of the RCN has been multi-dimensional and profound. For the principle investigators, the consortium has motived numerous collaborations and produced dozens of publications that have expanded their individual capabilities and the depth of their understanding on problems of common interest. For the trainees, both graduate students and postdoctoral fellows, the consortium has exposed them to new technologies and alternative perspectives on protein folding and dynamics. Regarding professional development, the students have been heavily involved in planning the annual meeting, organizing the program and leading the sessions. The meetings also provide an opportunity for building their professional networks with the PIs and their peers. Interestingly, some of the collaborations have been initiated by the trainees at the annual meeting. Finally, it is a hope of the consortium that our model for collective action on complex problems might serve as a paradigm for others in biology and science in general.
Last Modified: 09/01/2016
Modified by: C Robert Matthews
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