Structural Biophysics Laboratory

Chief
R. Andrew Byrd, Ph.D.

The Structural Biophysics Laboratory (SBL) focuses on solution structural biology and biophysics aimed at understanding and regulating the mechanism of action of proteins and nucleic acids. Our studies are targeted at important molecular pathways in cancer, particularly relating to invasiveness and metastasis. The major structural tool for the SBL is nuclear magnetic resonance (NMR), and the Laboratory has a very strong interdisciplinary effort in biophysics that includes Small Angle X-ray Scattering (SAXS) conducted through a Partnership User Program with the Advanced Photon Source at the Argonne National Laboratory. The SBL will be expanding with the addition of new PIs in 2013, which will broaden the scope of structural studies and their relationship to cancer. 

Byrd Lab: This laboratory uses NMR, biophysics and molecular biology to investigate the mechanisms of ubiquitination, specifically the interactions and regulations of ubiquitin conjugating enzymes (E2s) with ubiquitin ligases (E3s) involved in endoplasmic reticulum associated degradation (ERAD). Another significant project involves intracellular signaling via ADP-ribosylation factor (Arf) family GTP-binding proteins and their activators, the Arf GTPase-activating proteins (Arf GAPs). These projects are collaborative, involving CCR PIs, and focus on protein:protein interactions and the molecular mechanisms of action. Deciphering these mechanistic aspects provides opportunities for intervention.

Wang Lab: This laboratory explores structure-function relationships of RNA, RNA-protein and RNA:RNA complexes using NMR, SAXS, other biophysics, biochemical and biological tools and methods. The laboratory is currently focusing on the mechanism of how the HIV-1 virus recognizes its own mRNA and exports it out of nucleus for viral translation or packaging. This project is a collaboration with several CCR PIs. The laboratory also studies the mechanism of how 3' untranslated region (3' UTR) of mRNAs in human and in a model system involve in regulation of gene expression. Examples of such systems are 3' UTRs of the human vascular endothelial growth factor (VEGF) mRNA and the turnip crinkle virus (TCV) mRNA. Detailed structural information may lead to understanding of human diseases at the atomic level, thus potentially resulting in new revenues of therapeutic treatment.

Walters Lab: Projects in the Walters lab focus on how proteins are removed from cells. We are interested in how misfolded protein substrates are recognized and ubiquitinated by cellular surveillance systems and how ubiquitinated substrates are identified and processed by proteasome. We use a variety of biophysical techniques, our most powerful of which is NMR spectroscopy, to help develop a mechanistic understanding of how proteasome recognizes and processes its substrates. Our long-term goal is the manipulation of this process for proteins of interest, including oncoproteins and tumor suppressors.

Position Contact Name Contact E-mail Contact Phone Research Area Keywords Number of Positions
Tenure-Track Investigator Deanna Tabler

NCIFrederickSBLTenureTrackSearch@nih.gov

301-846-5199

X-ray diffraction, Cryo-electron microscopy

1
Postdoctoral Fellow Kylie Walters

kylie.walters@nih.gov

301-228-4374

cell biology, proteasome, ubiquitin, microscopy

1

Biophysics Resource

The Biophysics Resource (BR), operated by the Structural Biophysics Laboratory, provides CCR investigators with access to both the latest instrumentation and expertise in characterizing the biophysical aspects of systems under structural investigation.

The Biophysics Resource operates as an open, shared-use facility; in general, BR users learn to operate the instruments and conduct their own experients. Biophysics Resource staff members train all first-time users and are also available to consult with investigators on experimental design/analysis or collaborate with them on more complex studies.  To learn more, visit the Biophysics Resource.

SAXS Core Facility

The mission of the SAXS Core Facility is to provide support to research projects from CCR principal investigators (PIs), NIH intramural PIs and extramural academic research groups/laboratories. The support includes providing routine access to the APS PUP SAXS/WAXS beamline and in-house SAXS instrument, and expertise in experimental design, data collection, processing, analysis and interpretation. Our main focus is to determine the structure of biomacromolecules and their complexes in solution. The research field includes, but is not limited to, structural studies of nucleic acids, proteins, protein assemblies, virus particles, lipid membranes, protein/DNA and protein/RNA complexes. To learn more, visit the SAXS Core Facility.

About

The Structural Biophysics Laboratory (SBL) focuses on solution structural biology and biophysics aimed at understanding and regulating the mechanism of action of proteins and nucleic acids. Our studies are targeted at important molecular pathways in cancer, particularly relating to invasiveness and metastasis. The major structural tool for the SBL is nuclear magnetic resonance (NMR), and the Laboratory has a very strong interdisciplinary effort in biophysics that includes Small Angle X-ray Scattering (SAXS) conducted through a Partnership User Program with the Advanced Photon Source at the Argonne National Laboratory. The SBL will be expanding with the addition of new PIs in 2013, which will broaden the scope of structural studies and their relationship to cancer. 

Byrd Lab: This laboratory uses NMR, biophysics and molecular biology to investigate the mechanisms of ubiquitination, specifically the interactions and regulations of ubiquitin conjugating enzymes (E2s) with ubiquitin ligases (E3s) involved in endoplasmic reticulum associated degradation (ERAD). Another significant project involves intracellular signaling via ADP-ribosylation factor (Arf) family GTP-binding proteins and their activators, the Arf GTPase-activating proteins (Arf GAPs). These projects are collaborative, involving CCR PIs, and focus on protein:protein interactions and the molecular mechanisms of action. Deciphering these mechanistic aspects provides opportunities for intervention.

Wang Lab: This laboratory explores structure-function relationships of RNA, RNA-protein and RNA:RNA complexes using NMR, SAXS, other biophysics, biochemical and biological tools and methods. The laboratory is currently focusing on the mechanism of how the HIV-1 virus recognizes its own mRNA and exports it out of nucleus for viral translation or packaging. This project is a collaboration with several CCR PIs. The laboratory also studies the mechanism of how 3' untranslated region (3' UTR) of mRNAs in human and in a model system involve in regulation of gene expression. Examples of such systems are 3' UTRs of the human vascular endothelial growth factor (VEGF) mRNA and the turnip crinkle virus (TCV) mRNA. Detailed structural information may lead to understanding of human diseases at the atomic level, thus potentially resulting in new revenues of therapeutic treatment.

Walters Lab: Projects in the Walters lab focus on how proteins are removed from cells. We are interested in how misfolded protein substrates are recognized and ubiquitinated by cellular surveillance systems and how ubiquitinated substrates are identified and processed by proteasome. We use a variety of biophysical techniques, our most powerful of which is NMR spectroscopy, to help develop a mechanistic understanding of how proteasome recognizes and processes its substrates. Our long-term goal is the manipulation of this process for proteins of interest, including oncoproteins and tumor suppressors.

PI & Key Staff

Positions

Position Contact Name Contact E-mail Contact Phone Research Area Keywords Number of Positions
Tenure-Track Investigator Deanna Tabler

NCIFrederickSBLTenureTrackSearch@nih.gov

301-846-5199

X-ray diffraction, Cryo-electron microscopy

1
Postdoctoral Fellow Kylie Walters

kylie.walters@nih.gov

301-228-4374

cell biology, proteasome, ubiquitin, microscopy

1

Cores

Biophysics Resource

The Biophysics Resource (BR), operated by the Structural Biophysics Laboratory, provides CCR investigators with access to both the latest instrumentation and expertise in characterizing the biophysical aspects of systems under structural investigation.

The Biophysics Resource operates as an open, shared-use facility; in general, BR users learn to operate the instruments and conduct their own experients. Biophysics Resource staff members train all first-time users and are also available to consult with investigators on experimental design/analysis or collaborate with them on more complex studies.  To learn more, visit the Biophysics Resource.

SAXS Core Facility

The mission of the SAXS Core Facility is to provide support to research projects from CCR principal investigators (PIs), NIH intramural PIs and extramural academic research groups/laboratories. The support includes providing routine access to the APS PUP SAXS/WAXS beamline and in-house SAXS instrument, and expertise in experimental design, data collection, processing, analysis and interpretation. Our main focus is to determine the structure of biomacromolecules and their complexes in solution. The research field includes, but is not limited to, structural studies of nucleic acids, proteins, protein assemblies, virus particles, lipid membranes, protein/DNA and protein/RNA complexes. To learn more, visit the SAXS Core Facility.

Contact Info

Structural Biophysics Laboratory
Center for Cancer Research
National Cancer Institute
Building 538, Room 120
Frederick, MD 21702-1201
Ph: 301-846-1241
Administrative Lab Manager
301-846-1241