The Protein Expression Laboratory generates DNA, cell line, and protein reagents for biomedical research from basic science to drug discovery. The team uses cutting-edge protein production technologies to generate proteins using bacteria, insect cells, or mammalian cells at scales from micrograms to grams. 

Quality control is a major emphasis of the laboratory, ensuring that all protein reagents pass a series of stringent tests before leaving the group. The laboratory focuses on standardization and improvement to protein production technologies that are shared with the extramural research community. 

Novel technologies to boost protein yields and quality 

The Protein Expression Laboratory generated a variety of novel protein production technologies to improve protein yields and quality, and reduce the time needed to generate protein reagents. We specialize in challenging protein targets, including multiprotein complexes for structural biology and assay development, along with microscale technologies to minimize the cost and effort in protein production screening while allowing us to test larger numbers of proteins to identify optimal choices before large-scale production.  

Collaboration Opportunities

Access to Protein Expression Laboratory services is restricted to NIH/intramural researchers.  However, new technologies and materials generated at PEL are available to academic researchers through Materials Transfer Agreements and to for-profit researchers through licensing. In addition, some materials related to COVID-19 protein production are available via Technical Service Agreements.  

We are open to collaborations with researchers on technology development projects related to our mission to improve protein production processes. Such collaborations can occur through academic collaboration agreements or cCRADA agreements with for-profit researchers through the Partnership Development Office

Contact Dr. Dom Esposito to ask about engaging our services. 

Scientist placing samples into a machine
IP available for licensing

Technologies for improved protein production in insect cells

A variety of inventions related to improvements in protein production using insect cell culture systems are available for distribution to nonprofit researchers or licensing to for-profit entities. These include novel cell lines for high-level protein production, second generation systems for baculovirus production, and rapid methods for titration of baculoviruses.

Proteins for critical national initiatives 

In support of the NCI RAS Initiative, the Protein Expression Laboratory generates reagents for producing multiprotein complexes involved in the RAS activation pathway. These complexes are being investigated to better understand their role in RAS signaling and to determine three-dimensional structures to enable drug discovery. 

To assist NCI SeroNet researchers, we generated diverse COVID-19-related proteins for serological assay development and deployment.   

Our scientists support the Antivirals for Pandemic Preparedness program with the National Center for Advancing Translational Sciences (NCATS) by generating recombinant proteins representing potential drug targets of a variety of potentially pandemic viruses.  


Publications highlight tech developments  

The Protein Expression Laboratory publishes novel technology developments as stand-alone manuscripts and contributes to publications by other RAS Initiative and NIH intramural collaborators in which our distinct if not unique reagents are highlighted. 

Reagents developed by the RAS Reagents Group
Fully modified KRAS protein

Reagents for research on RAS and the RAS pathway

Unique reagents developed by RAS Initiative researchers are available to the RAS community.
Standardization graphic
SOPs and reference materials

Protein production standards for reproducible results

Standardized methods for protein production and processes to ensure quality control of protein reagents are both essential for high-quality research. Download Protein Science standards at the Frederick National Laboratory Scientific Standards Hub.

Our capabilities and specializations

Additional Content

Structural biology applications 

We produce high-quality individual recombinant proteins and protein complexes and optimize protein constructs using microscale expression and purification to quickly identify the optimal protein domains for production. Proteins can readily be labelled with isotopes. 

Additional Content
  • X-ray crystallography 

  • Nuclear magnetic resonance 

  • Cryo-electron microscopy 

Additional Content

Support drug discovery assay development and deployment 

We generate proteins with a variety of domain designs and tagging strategies to support biochemical and biophysical drug discovery assays. Our collection of more than 100 different fusion protein tags ranges from various fluorescent proteins to antibody-based detection tags. 

Additional Content
  • Surface plasmon resonance 

  • Homogenous time-resolved fluorescence 

  • Fluorescence polarization 

  • Isothermal calorimetry 

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New technologies for enhanced protein production 

We develop new reagents to improve production of proteins from insect cells and use specialized cloning processes to permit multi-gene assembly assist in the production of large multiprotein complexes for structural biology and drug discovery. We use magnetic bead technologies to accelerate protein purification timelines and reduce cost, as well as new expression systems to provide additional options for challenging protein targets. 

Additional Content
  • Novel high-producing cell lines 

  • Modified DNA constructs for faster and more efficient baculovirus production 

  • Chaperones to assist with better recombinant protein folding 

A researcher examines Coomassie stained polyacrylamide gels to monitor protein purification status.
A researcher examines Coomassie stained polyacrylamide gels to monitor protein purification status.
Researcher looking at a sample
Angélica Mercado-Torres, Research Associate, examines a sample of purified protein for quality control.
Scientist putting beaker of bacteria culture into laboratory hood
Nitya Ramakrishnan, Research Associate, loads a bacterial culture of E. coli cells into a shaking incubator to generate proteins.
Scientist working with a centrifuge
Matt Smith, Research Associate, removes samples of purified proteins from a high-speed centrifuge.
Scientist pours liquid at a lab bench.
Morgan Pagonis, Research Associate, filter sterilizes a buffer which will be used for protein purification.
Scientist works at protein expression machine
Phuong Vi Le, Research Associate, programs a fermentor for high-density bacterial cell growth.
Scientist works at a protein purification system.
A 15-liter bacterial fermentor sits ready to produce hundreds of miligrams of protein from E. coli.
FPLC system.
A Fast Performance Liquid Chromatography (FPLC) system used for large-scale purification of recombinant proteins