Structural Biophysics Laboratory

Acting Chief
Kylie J. Walters, Ph.D.

The Structural Biophysics Laboratory (SBL) was established in 1999 to conduct basic research that yields structure-based insights of the biophysics and mechanisms of action and regulation for biological systems of significant functional impact. This approach is used by SBL investigators to provide insights into the function and dysfunction of proteins and nucleic acids, particularly in relation to human cancers and HIV. Results are used to understand disease mechanisms and ultimately to provide new therapeutic strategies. The Laboratory features exceptional expertise and state-of-the-art instrumentation for NMR spectroscopy, small angle x-ray scattering (SAXS), diffraction methods (both conventional and x-ray free electron laser (XFEL)), cryoelectron microscopy, and a wide range of biophysical methods to characterize biomolecular interactions and targeting. The SBL established and supports the Biophysics Resource and SAXS Core, each of which provide intellectual and resource support to a large number of CCR, NIH, and academic investigators.

The SBL contains four independent laboratory sections that apply quantitative and structural approaches to unique biological systems.

Kinase Complexes Section (Dr. Ping Zhang, Chief): This lab studies the structural and mechanistic basis of kinases closely related to human cancers and Parkinson's disease. We apply interdisciplinary approaches spanning many fields such as cryoEM, X-ray crystallography, solution methods, biochemistry, cell signaling and post-translational modification, etc. We aim to combine structural and functional studies to reveal the molecular mechanism of kinase complexes' dysfunction and help develop novel reagents that may eventually lead to a cure for cancer and other diseases.

Macromolecular NMR Section (Dr. R. Andrew Byrd, Chief): 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.

Protein Nucleic Acid Interactions Section (Dr. Yun-Xing Wang, Chief): 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.

Protein Processing Section (Dr. Kylie J. Walters, Chief): 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.


There are no Open Positions at this time, check back again later.


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.

Accolades

  • Dr. Yun-Xing Wang received the 2017 Director’s Award for his exciting work applying XFEL to riboswitches
  • Dr. Yun-Xing Wang was awarded the NCI 2017 Federal Technology Transfer Award

Leadership Evolution at SBL

After receiving a rating of ‘outstanding’ from the SBL site visit review panel, our founding Chief, Dr. R. Andrew Byrd, has decided to step down to focus on his research program. His work is providing foundational insights into allosteric and dynamic mechanisms that control the ubiquitination pathway as well as mechanisms of molecular recognition and regulation of Arfs and Arf-GTPase Activating Proteins at the membrane surface. Andy has been Chief since 1999 and under his leadership, the SBL has grown to its current strength of 4 PIs (all of whom are leaders in their research area), established world class facilities and spearheaded a multidisciplinary approach that has provided powerful mechanistic insights into complex biological process. Dr. Kylie J. Walters will serve as Acting Chief while an international search is conducted to identify Andy’s successor. Kylie joined the SBL as a Senior Investigator in 2013.


2016 Structural Biology Retreat

We had a fantastic 2016 Structural Biology Retreat that was interactive and motivating. The day began with distinguished outside speaker Professor Juli Feigon presenting her integrative structural biology approach to define the Tetrahymena telomerase structure and in turn, make profound mechanistic insights into its function. Yifei Li (from Andy Byrd’s lab) introduced his plans to study a protein complex in a nanodisc to mimic the membrane environment, Kedar Narayan highlighted ongoing efforts in the CMM and its availability to CCR investigators, He Song (from Xinhua Ji’s lab) presented very nice data on a ribonucleoprotein, Kylie Walters presented her ongoing efforts to define new therapeutic sites in the proteasome, Yun-Xing Wang described his success in performing a real time determination of the structure of an intermediate state using XFEL, Di Xia presented his ongoing work to define drug resistance mechanisms for a P-glycoprotein, and newly hired Ping Zhang put forth ambitious plans for her new lab. The poster sessions displayed exciting ongoing projects, with Xiang Chen, Frank Chao, and Sathiya Dharmaiah/Timothy Tran selected for Outstanding Poster Awards. Special thanks to Sergey Tarasov and Kylie Walters for organizing, as well as Cindy Castle, Lori Larson and Team Help for making the day a success.


MOVING: SBL will be relocating to the ATRF building in Frederick, fall 2016, to make way for renovation of Building 538. NMR facilities will remain operational adjacent to Bldg. 538 and SBL looks forward to returning to new labs in 2018.


2016 Statdman Tenure-track PI

The SBL is pleased to announce the arrival of Dr. Ping Zhang as a Stadtman Tenure-Track PI. Ping joined the SBL in August 2016, and she will initiate a research program combining cryoEM and crystallography in the study of complexes regulating kinase activity. The group has already recruited two new postdoctoral fellows. Please contact Ping Zhang if you are interested in joining her research group.


2015 Structural Biology Retreat

Dr. Kylie Walters organized the retreat in October 2015, bringing together PIs with interest in structural biology from the Frederick campus (both Ft. Detrick and ATRF sites) and the Bethesda campus. It was an exciting day of talks and posters, and it will become an annual event. Please watch for dates and join in!

Structural Biology Retreat - October 2015

 

 

 

 

 

 

 

Structural Biology Retreat, October 2015, brings together researchers from multiple disciplines across the Frederick and Bethesda campuses of NCI.

About

The Structural Biophysics Laboratory (SBL) was established in 1999 to conduct basic research that yields structure-based insights of the biophysics and mechanisms of action and regulation for biological systems of significant functional impact. This approach is used by SBL investigators to provide insights into the function and dysfunction of proteins and nucleic acids, particularly in relation to human cancers and HIV. Results are used to understand disease mechanisms and ultimately to provide new therapeutic strategies. The Laboratory features exceptional expertise and state-of-the-art instrumentation for NMR spectroscopy, small angle x-ray scattering (SAXS), diffraction methods (both conventional and x-ray free electron laser (XFEL)), cryoelectron microscopy, and a wide range of biophysical methods to characterize biomolecular interactions and targeting. The SBL established and supports the Biophysics Resource and SAXS Core, each of which provide intellectual and resource support to a large number of CCR, NIH, and academic investigators.

The SBL contains four independent laboratory sections that apply quantitative and structural approaches to unique biological systems.

Kinase Complexes Section (Dr. Ping Zhang, Chief): This lab studies the structural and mechanistic basis of kinases closely related to human cancers and Parkinson's disease. We apply interdisciplinary approaches spanning many fields such as cryoEM, X-ray crystallography, solution methods, biochemistry, cell signaling and post-translational modification, etc. We aim to combine structural and functional studies to reveal the molecular mechanism of kinase complexes' dysfunction and help develop novel reagents that may eventually lead to a cure for cancer and other diseases.

Macromolecular NMR Section (Dr. R. Andrew Byrd, Chief): 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.

Protein Nucleic Acid Interactions Section (Dr. Yun-Xing Wang, Chief): 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.

Protein Processing Section (Dr. Kylie J. Walters, Chief): 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


There are no Open Positions at this time, check back again later.


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
Advanced Technology Research Facility (ATRF)/B2400
Frederick, MD 21702-1201
Ph: 301-846-1241
Administrative Lab Manager
301-846-1241