The National Institutes of Health has selected 16 finalists for Phase 1 of its Follow that Cell Challenge. The goal of the challenge is to stimulate the development of new tools and methods that will enable researchers to predict the behavior and function of a single cell in complex tissue over time. This ability could help reveal valuable information such as how cells transition from a healthy to diseased state, or identify changes that influence a cell’s responsiveness to treatment. In addition, non-destructive methods for monitoring single cells could assist with early disease detection and allow doctors to better tailor therapies to cells as they evolve throughout the course of a disease.
During Phase 1 of the challenge, innovators across a wide range of fields were encouraged to propose theoretical solutions for tracking and analyzing the behavior and function of individual cells over a period of minutes, hours, and even days. Of the 16 finalists, five prize winners were selected to receive monetary prizes totaling $88,000 and will now advance—along with the additional 11 finalists—to the challenge’s second phase, which requires innovators to generate proof-of-concept data.
“This is the first challenge of this magnitude, not just for the NIH Common Fund, but for the NIH in general. The challenge seeks to stimulate novel approaches to probing individual cell behavior and function over time, which can lead to fundamental new insights into disease processes and, eventually, treatments,” said James M. Anderson, M.D., Ph.D., director of the NIH’s Division of Program Coordination, Planning, and Strategic Initiatives, which houses the NIH Common Fund. “Through the unique challenge mechanism, we hope to tap into investigators’ ideas not typically reached through traditional avenues of NIH funding. Based on the intriguing and innovative solutions proposed by the phase 1 finalists, this seems to be true. We look forward to what will be achieved through phase two of the challenge.”
Phase 1 solutions were submitted last December by individuals or teams. The Follow that Cell Challenge is part of the America COMPETES initiative and was issued by the National Institute of Mental Health (NIMH) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB), on behalf of the NIH Common Fund’s Single Cell Analysis Program. The submissions were evaluated by scientific experts from across the NIH and then reviewed by a three-judge panel.
“The large number of highly novel solutions that were proposed underlines the benefits of reaching out to innovators across many different fields. There is tremendous power in merging concepts and expertise from engineering, chemistry, and molecular biology to solve challenging issues in biomedical research. These innovative solutions are a prime example of that power,” said Roderic Pettigrew, Ph.D., M.D., director of NIBIB. “The successful development of any of the selected projects would have a very large impact on our understanding of health and disease states. We are eager for each to be carried forward.”
“Like the BRAIN Initiative grants we awarded last Fall, these projects represent the best of ‘out-of-the-box’ thinking by some of the most talented minds in the field,” added NIMH director Thomas R. Insel, M.D.
Phase 2 begins on March 17, 2015 and is open only to the 16 finalists. During Phase 2, Reduction to Practice, finalists will generate proof-of-concept data related to their Phase 1 entries. These submissions are due March 30, 2017. Winners of Phase 2 will be awarded prize money from a pool of $400,000, to be announced July 31, 2017.
The Phase 1 prize winners will be presented and recognized as part of the 3rd Annual Single Cell Analysis Investigators Meeting, which is scheduled for April 20-21, 2015 at the Natcher Conference Center on the NIH Campus in Bethesda, Maryland.
Although final verification of eligibility is still pending, a list of proposed finalists and brief descriptions of the five prize-winning solutions can be found below. For more information about these projects and descriptions of all the finalists’ projects, please visit the Single Cell Analysis Program website.
FIRST PLACE PRIZE WINNER:
Single cell timelapse gene expression profiling via an engineered self-reporting pathway
Paul Blainey, Ph.D. (team lead), MIT and Broad Institute, Cambridge, Massachusetts
The researchers propose to engineer an RNA export pathway that can capture a small amount of a cell’s mRNA, label it with a unique barcode, and then secrete it out of the cell. The secreted mRNA can then be collected from the extracellular environment and analyzed at different time points to determine how gene expression in one cell changes over time. The technique is integrated with microscopic imaging so that the changes in the cell’s gene expression can be correlated with changes in its phenotype.
ADDITIONAL PRIZE WINNERS:
Self-destructing cellular barcode: a versatile tool for single cell analysis
James Ankrum, Ph.D., University of Iowa, Iowa City, Iowa
Of critical importance for studying single cell activity is the ability to identify and track a single cell over time. This solution proposes a method for uniquely labelling thousands of single cells. The proposed label lasts for several weeks, is transferred to cell progeny, and self-destructs when the cell dies. The technique would be useful for determining stem cell fate and lineage.
Measuring protein concentrations and protein translation over time in single cells in vivo
Brian Chen, Ph.D., McGill University, Montréal, Québec
The amount of protein that a cell produces is tightly regulated; too little or too much of a single protein can lead to disease. The ability to understand how protein production affects cell phenotype is an important step in understanding how diseases occur. This solution proposes to develop a technique for tracking and measuring protein production in single cells of living animals. Such a technique would permit researchers to measure real-time changes of protein production within a cell’s native environment at unprecedented resolution.
BLINKER assessed live cell transcriptomics
James Eberwine, Ph.D., (team lead), University of Pennsylvania, Philadelphia, Pennsylvania
This solution proposes the development of a sensor called Blinker to visualize the transcription of genes in real time in live neurons. The sensor is comprised of a peptide that produces a detectable flash when bound to a specific sequence on a newly transcribed mRNA molecule. For any given mRNA molecule, the distance between flashes will be different and this unique pattern can be used to identify the gene that is being expressed. The ability to visualize and identify the synthesis of many mRNA molecules over a period of minutes could yield important information about which genes are important during long-term potentiation and how the expression of certain genes affects the responsiveness of neurons to drugs.
Study the longitudinal expression of the genome of a single cell
Nader Pourmand, Ph.D., University of California Santa Cruz, Santa Cruz, California
This solution proposes the use of a nano-sized pipette whose tiny tip can retrieve miniscule samples of a cell without perturbing its health, function, or gene expression. The pipette takes many repetitive cell samples over a period of minutes, hours, days, or weeks. These small samples can then be analyzed to monitor changes in gene expression that occur as a cell ages or undergoes other phenotypic changes.
Though not recipients of a monetary prize, the following meritorious solutions were selected to move on to Phase 2 of the competition.
- Next generation automated cell tracking software to Follow That Cell and its progeny accurately in complex multicellular environments
Helen Blau, Ph.D. (team lead), Stanford University, Stanford, California
- Development, optimization, and enhancement of fluorescent DNA-hairpin functionalized gold nanoparticles as imaging tools
Joseph Conrad, Ph.D. (team lead), Vanderbilt University, Nashville, Tennessee
- Microfluidic droplet based platform for cell co-encapsulation and monitoring
Tania Konry, Ph.D., Northeastern University, Boston, Massachusetts
- Synthetic nano-antibodies for real-time monitoring of cellular biomarkers
Markita Landry, Ph.D., MIT, Cambridge, Massachusetts
- Single cell oncogenesis
Xin Lu, Ph.D., MD Anderson Cancer Center, Houston, Texas
- Tracking the phenotype of single cells using multicolor flow cytometry combined with cell-specific barcodes
Garry Nolan, Ph.D., Stanford University, Stanford, California
- Flow of mechanical information in living cells
Frederick Sachs, Ph.D. (team lead), State University of New York at Buffalo, Buffalo, New York
Hongjun Song, Ph.D. (team lead), Johns Hopkins University, Baltimore, Maryland
- Dynamic tracking of cancer stem cells in native tumor microenvironments - single cell, dynamic monitoring of multi-gene expression in tumor tissues
Pak Kin Wong, Ph.D. (team lead), University of Arizona, Tucson, Arizona
- Photostable multiplexing nanoassays for real-time molecular imaging of single live cells
X. Nancy Xu, Ph.D., Old Dominion University, Norfolk, Virginia
- Development of micro-scale sampling probes for in situ mass spectrometry analysis of secretomes from live single cells
Zhibo Yang, Ph.D., University of Oklahoma, Norman, Oklahoma
About the Common Fund: The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Common Fund can be found at http://commonfund.nih.gov
About the National Institute of Biomedical Imaging and Bioengineering: NIBIB’s mission is to improve health by leading the development and accelerating the application of biomedical technologies. The Institute is committed to integrating the physical and engineering sciences with the life sciences to advance basic research and medical care. NIBIB supports emerging technology research and development within its internal laboratories and through grants, collaborations, and training. More information is available at the NIBIB website: http://www.nibib.nih.gov.
About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit http://www.nimh.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.