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�����ƽ��leads the charge on developing new research tools that have broad applications, pushing the boundaries on multiple research fronts.

Small Molecule Screening

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Thanks to NIH, publicly funded researchers now have access to resources and tools with the capacity to screen large numbers of small molecules, helping them to more efficiently study genes and discover treatments for human diseases. Researchers used these resources to develop FDA-approved treatments for ulcerative colitis and relapsing forms of multiple sclerosis.

Image credit: National Center for Advancing Translational Sciences, NIH

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• This advancement in small molecule research makes it easier for scientists to use and understand molecular compounds in basic research and drug development.
• The �����ƽ��Common Fund Molecular Libraries and Imaging Program also launched PubChem, an open chemistry database that contains information on chemical structures, properties, and biological activities of over 100 million compounds, including small molecules.��
• �����ƽ��also developed tools and resources to help scientists conduct preclinical research, with a focus on small molecule screening.

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Single Cell Analysis

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�����ƽ��fostered a technological revolution in single cell analysis research, leading to the development of cutting-edge tools, methods, platforms, and cell atlases to identify and characterize features of single cells within a variety of human tissues. These technologies are available to the entire research community to foster additional breakthroughs in research.

Image credit: NIH

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• The human body contains approximately 37 trillion cells, carefully organized in tissues to carry out the daily processes that keep the body alive and healthy. Analysis of single cells poses many technological challenges.
• Between 2012 and 2017, the �����ƽ��Common Fund Single Cell Analysis Program found a three-fold increase in the number of single cell analysis projects funded by �����ƽ��and an approximate doubling of relevant publications.��
• Understanding cells at the individual level may lead to new understandings of development, health, aging, and disease.

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Cryo-EM

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�����ƽ��funded the development and dissemination of cryo-electron microscopy (cryo-EM), a tool that enables high-resolution images of proteins and other biological structures. Cryo-EM has helped researchers identify potential new therapeutic targets for vaccines and drugs.

Image credit: Huilin Li, Brookhaven National Laboratory, and Bruce Stillman, Cold Spring Harbor Laboratory

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• An NIH-funded researcher was awarded the 2017 Nobel Prize in Chemistry for their work characterizing proteins using cryo-EM.��
• Since 2018, the NIH-supported National Centers for Cryo-EM enabled researchers to determine the structure of more than 300 proteins, including the SARS-CoV-2 spike protein, and trained more than 1,000 investigators in this cutting-edge technique.

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Cell Culture Technology

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�����ƽ��scientists created Matrigel, a specialized gel that promotes cell growth on a 3-D surface that mimics the environment within the body. Today, Matrigel is widely used in labs around the world to study cells that were previously impossible to grow and to investigate complex cell activities in a more relevant environment.

Image credit: David Sone

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• Prior to this invention, scientists grew cells in a flat layer in plastic culture dishes, which was not sufficient to grow specialized cells, like stem cells.
• Using Matrigel, researchers discovered new insights into nerve growth, the formation of blood vessels, and stem and cancer cell biology. It is also being used to screen cancer drugs and to support development of artificial tissues that can mimic organ function.��
• More than 13,000 scientific papers have cited the use of Matrigel in their studies.

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Cancer Genome Atlas

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The Cancer Genome Atlas (TCGA) is a landmark �����ƽ��cancer genomics program that transformed our understanding of cancer by analyzing tumors from 11,000 patients with 33 different cancer types. Findings from TCGA identified new ways to prevent, diagnose, and treat cancers, such as gliomas and stomach cancer.

Image credit: Darryl Leja, National Human Genome Research Institute, NIH

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• TCGA showed that different cancers can share molecular traits regardless of the organ or tissue they are found in. This enabled the emergence of precision medicine in oncology—cancer treatment based on molecular traits rather than the tissue in the body where the cancer started.
• TCGA generated over 2.5 petabytes (1 petabyte = 500 billion pages of standard printed text!) of data on genes, proteins, and their modifications in cancer by bringing together 20 collaborating institutions across the U.S. and Canada.

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Recombinant DNA

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Because of NIH-funded research on recombinant DNA technology, researchers developed techniques that can enable the production of large quantities of important peptides—the building blocks of proteins—which can be used to produce certain medicines.

Image credit: National Human Genome Research Institute, NIH

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• Scientists use specialized molecules to snip out a specific gene from a long strand of DNA, creating recombinant DNA by inserting it into bacterial or yeast cells. These cells reproduce quickly and, following the gene’s instructions, make large amounts of the desired peptide.
• These techniques enabled the production of synthetic insulin to treat diabetes.
• Medicines produced using these techniques have been used for more than 30 years.
• In 1980, an NIH-funded researcher received a Nobel Prize for research on recombinant DNA.

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Imaging Technology

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Significant innovation in clinical imaging technology is a result of NIH-funded research. Imaging technologies now have higher resolution and greater sensitivity, with new categories of imaging, like digital 3D reconstructions, now being commonly used.

Image credit: Clinical Center, NIH

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• A new type of positron emission tomography (PET) that looks for prostate cancer specific proteins has been found to be 27% more accurate than standard methods for detecting prostate cancers.
• NIH-supported improvements in PET technologies resulted in a more sensitive technology that can capture scans in under a minute and reduce the dose of dye given to patients.
• NIH-funded research led to the development of nuclear magnetic resonance imaging, which won a Nobel Prize, and is the same technique used in MRIs in clinical settings.

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Tissue Chips

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�����ƽ��investment in tissue chips—3D cellular platforms that model the structure and function of human organs—has made drug screening faster, more accurate, and more accessible, and enabled researchers to study drugs in models that were previously hard to replicate.

Image credit: NASA Photo/Josh Valcarcel

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• Tissue chips, or “organs-on-chips,” support the growth and function of living human cells and tissues, modeling organs such as the lung, liver, and heart.
• In collaboration with the International Space Station National Laboratory and NASA, �����ƽ��sends tissue chips to space for astronauts to use in research. To enable this, the complex technology was automated and miniaturized—from the size of a refrigerator to the size of a shoebox.
• Because exposure to microgravity in space causes similar effects as aging, researchers can develop models of aging within weeks or months in space compared to years or decades on earth.

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Click Chemistry

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�����ƽ��support led to the development of “click chemistry”—a fast and reliable way to snap together molecular building blocks—enabling researchers to construct molecules with more specificity and efficiency, advancing biomedical research on many fronts, from cancer to infectious disease.

Image credit: Carolyn Bertozzi, University of California, Berkeley

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• NIH-funded researchers who developed click chemistry techniques won the Nobel Prizes in Chemistry in 2021 and 2022.
• Understanding how to construct organic molecules has greatly expanded our ability to explore the molecular underpinnings of a wide range of biological processes, and it has provided researchers with new tools for developing drugs and diagnostics, including for cancer.
• Using click chemistry, strychnine—a molecule used in antidepressants and antivirals—can be synthesized in just 12 steps compared to 29 using traditional methods, in a process that is 7,000 times more efficient.

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References

Small Molecule Screening

1. Molecular Libraries and Imaging: 
2. Preclinical Research Toolbox: 
3. �ʳܲ�����:��
4. Molecular Libraries and Imaging Program Highlights: 
5. Article: Ozanimod accepted for priority review by FDA for the treatment of ulcerative colitis: 
6. Article: U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Zeposia® (ozanimod), an Oral Treatment for Adults with Moderately to Severely Active Ulcerative Colitis: 

Single Cell Analysis

1. �����ƽ��Single Cell Analysis Program: 
2. Roy AL, et al.��Sci Adv. 2018;4(8):eaat8573. PMID: .
3. The Human BioMolecular Atlas Program: 
4. HuBMAP Data Portal: 
5. Cellular Senescence Network: 
6. ���ܲԲ��Ѵ���:��
7. GenitoUrinary Development Molecular Anatomy Project: 

Cryo-EM

1. Transformative High-Resolution Cryoelectron Microscopy Program: 
2. Cryo-Electron Microscopy Program Centers: 
3. Zhang K, et al.��bioRxiv [Preprint]. 2020:2020.08.11.245696. Update in: QRB Discov. 2020;1:e11. PMID: .��
4. �����ƽ��Nobel Laureates: /about-nih/what-we-do/nih-almanac/nobel-laureates
5. Cressey D, et al.��Nature. 2017;550(7675):167. PMID: .

Cell Culture Technology

1. Simian M, et al.��J Cell Biol. 2017;216(1):31-40. PMID: .
2. Article: An Interview with Hynda Kleinman: 
3. Kleinman HK, et al.��Semin Cancer Biol. 2005;15(5):378-86. PMID: .
4. Article: Hair today, gone tomorrow: NIDCR'S Hynda Kleinman takes off for new horizons: 

Cancer Genome Atlas

1. The Cancer Genome Atlas Program: 

Recombinant DNA

1. NIGMS-Supported Nobelists: 
2. Article: Celebrating the discovery and development of insulin: 
3. National Institute of General Medical Sciences.��The New Genetics. 2010.��

Imaging Technology

1. Article: Commemorating the 50th Anniversary of the National Cancer Act (NCA50): Clinical Imaging — Then and Now: 
2. EXPLORER Total Body PET Scanner: 
3. Badawi RD, et al.��J Nucl Med. 2019;60(3):299-303. PMID: .
4. Article: PSMA PET-CT Accurately Detects Prostate Cancer Spread, Trial Shows: 
5. NIGMS-Supported Nobelists: 
6. Magnetic Resonance Imaging (MRI): 

Tissue Chips

1. Tissue Chip Projects & Initiatives:
2. Article: NIH-funded tissue chips rocket to International Space Station: /news-events/news-releases/nih-funded-tissue-chips-rocket-international-space-station
3. Article: Researchers create 3-D model for rare neuromuscular disorders, setting stage for clinical trial: /news-events/news-releases/researchers-create-3-d-model-rare-neuromuscular-disorders-setting-stage-clinical-trial
4. Translational Centers for Microphysiological Systems (TraCe MPS) (U2C Clinical Trials Not Allowed):

Click Chemistry

1. The Nobel Prize in Chemistry 2021:
2. The Nobel Prize in Chemistry 2022:
3. Article: The Chemistry Clicked: Two NIGMS-Funded Researchers Receive Nobel Prize:
4. Article: The Chemistry Clicked: Two NIH-Supported Researchers Win 2022 Nobel Prize in Chemistry: