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Principal Investigator: Richard Edward Gillilan
Organization: CORNELL UNIVERSITY
Fiscal Year: 2024
Award: $1,589,509
Funding agency: National Institute of General Medical Sciences
Project summary:
The MacCHESS Synchrotron Source for Structural Biology facilitates the utilization of both
established and emerging technologies to enable the structural characterization of proteins involved in
critically important biological processes with significant consequences for diseases such as cancer, bacterial
and viral infections, and neurodegenerative disorders. Recent upgrades to CHESS, including improvements
to the storage ring and newly designed beamlines have provided state-of-the-art facilities and enabled
greater capabilities since June 2019. MacCHESS will continue to support more than 100 investigator
projects, funded by NIH and other government institutions, through two major Technology Operations Cores.
These are: 1) Facility for Flexible Crystallography, which will take advantage of unique MacCHESS
capabilities to enable the development of new X-ray techniques that may be used to broaden our knowledge
of essential biological processes. Examples include continued development of methods for room
temperature crystallography toward identifying new structural or ligand/drug binding states, the application
of high pressure to crystals, and analysis of macromolecular motions through the study of X-ray diffuse
scattering. A high level of support for more routine macromolecular crystallography will also be provided.
These methods will help to provide important new insights including the binding interactions and
conformational transitions that cell signaling proteins and drug targets undergo which are necessary for their
function, and the macromolecular motions essential for the catalytic activities of enzymes that regulate key
metabolic processes, DNA transcription and repair, and different aspects of RNA biology. 2) Facility for
Biological Small Angle X-ray Scattering (BioSAXS), which will implement state-of-the-art hardware,
software, and expertise to support the BioSAXS technique that continues to be in high demand. In addition
to determining the shapes of proteins, nucleic acids, and larger protein assemblies in solution, BioSAXS
allows researchers to obtain information regarding global conformational changes within macromolecular
complexes (e.g., membrane receptors, RNA-splicing complexes, large or multi-subunit enzymes) and the
changes in their oligomeric states that have important functional consequences. This core will also provide
the necessary equipment and expertise for investigators interested in performing time resolved BioSAXS or
BioSAXS studies conducted under high pressure. MacCHESS will provide a strong Administration Core to
support these activities and will continue to educate and help to train users and investigators from the
biomedical research community new to the field of structural biology, through a Training and Outreach Core.
Collectively, these efforts will offer unique opportunities to our users for pursuing some of the most
challenging questions in structural biology and for obtaining structure-function information that will ultimately
highlight novel therapeutic targets and aid in the development of clinical strategies for dealing with disease.
Terms: <Address><Adeno-Associated Viruses><Area><Automobile Driving><Bacterial Infections><Behavior><Binding><Biological><Biological Function><Biological Process><Biology><Biomedical Research><Biophysics><Calibration><Cancers><Cell Communication and Signaling><Cell Signaling><Clinical Treatment Moab><Communities><Complex><Computer software><Consumption><Coupled><Crystallographies><Crystallography><Custom><DNA><Degenerative Neurologic Disorders><Deoxyribonucleic Acid><Dependoparvovirus><Dependovirus><Development><Diffuse><Disease><Disorder><Drug Targeting><Drugs><Education and Outreach><Educational workshop><Emergent Technologies><Emerging Technologies><Ensure><Enzyme Gene><Enzymes><Equipment><Funding><Gene Transcription><Generalized Growth><Genetic Transcription><Goals><Government><Growth><Home><Hour><Institution><Instruction and Outreach><Intermediary Metabolism><Intracellular Communication and Signaling><Investigators><Ion Channel><Ionic Channels><Knowledge><Learning><Ligands><Liquid substance><Macromolecular Complexes><Malignant Neoplasms><Malignant Tumor><Medication><Membrane><Membrane Channels><Metabolic Processes><Metabolism><Methodology><Methods><Modeling><Molecular><Molecular Configuration><Molecular Conformation><Molecular Interaction><Molecular Sieve Chromatography><Molecular Stereochemistry><Monoclonal Antibodies><Monoclonal Antibody Therapy><Motion><NIH><National Institutes of Health><Nature><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Non-Polyadenylated RNA><Nucleic Acids><O element><O2 element><Oxygen><Peer Review><Pharmaceutical Preparations><Phase><Physiologic><Physiological><Play><Preparation><Process><Productivity><Property><Proteins><Publications><Quality Control><RNA><RNA Expression><RNA Gene Products><RNA Splicing><Receptor Protein><Research><Research Personnel><Researchers><Resolution><Ribonucleic Acid><Roentgen Rays><Role><Sampling><Scientific Publication><Services><Shapes><Signal Transduction><Signal Transduction Systems><Signaling><Signaling Factor Proto-Oncogene><Signaling Pathway Gene><Signaling Protein><Site><Size Exclusion Chromatography><Software><Source><Speed><Splicing><Structure><Students><Synchrotrons><System><Techniques><Technology><Temperature><Therapeutic><Time><Tissue Growth><Training><Training and Outreach><Transcription><Tutoring and Outreach><United States National Institutes of Health><Viral Diseases><Virus Diseases><Visit><Work><Workshop><X-Radiation><X-Ray Radiation><X-ray><Xray><adeno associated virus group><bacteria infection><bacterial disease><base><bases><beamline><biologic><biological signal transduction><biophysical foundation><biophysical principles><biophysical sciences><clinical development><computerized data processing><conference><conformation><conformational><conformational conversion><conformational state><conformational transition><conformationally><conformations><convention><customs><data collection site><data processing><data reduction><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><design><designing><detection sensitivity><developmental><driving><drug/agent><enzyme activity><experience><flexibility><flexible><fluid><homes><improved><insight><instrumentation><interest><lectures><lipid based nanoparticle><lipid nanoparticle><liquid><mAB-based therapy><mAb therapy><mAb-based therapeutics><mAbs><magnetic field><malignancy><membrane structure><metalloenzyme><method development><monoclonal Abs><neoplasm/cancer><neurodegenerative illness><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><ontogeny><operation><operations><outreach><preparations><pressure><program dissemination><programs><project dissemination><protein complex><receptor><repair><repaired><resolutions><social role><structural biology><success><summit><symposia><symposium><user-friendly><viral infection><virus infection><virus-induced disease>