The Southeastern Center for Microscopy of MacroMolecular Machines (SECM4) is a consortium of 15 Universities/Medical Centers with a total of 19 investigators throughout the Eastern United States studying a wide range of important biomedical projects as variable as high resolution virus structure, membrane protein structure, macromolecular complexes of various types, some isolated in active form from cells, bacterial ultrastructure, muscle filaments, spliceosomes, ribosomes complexes all of which will benefit from ready access to a high resolution electron microscope such as a Titan Krios equipped with a direct electron detector (DED). Human health implications extend from virus and bacterial pathogens to the understanding of diseases resulting form genetic mutations. The basic biology of cancer and heart disease is being studied in several member laboratories. The Titan Krios at Florida State University has been in operation since 2009 and recently has had its image recording device upgraded from CCD camera to a Direct Electron LLC, DE-20 direct electron detector positioned ahead of an existing imaging filter which removes inelastically scattered electrons thereby improving the image quality. Although we propose a robust plan to enable members to come to Florida State University, we propose creating a facility based on the synchrotron template currently in use at multiple sites X-ray crystallography beam lines around the country whereby users ship specimens to us and watch the data being collected as it comes off the microscope from the familiar confines of their own laboratories. We will provide sufficient preprocessing that consortium members can evaluate the prospects for obtaining a final high resolution structure from damage and motion corrected ?movie? images of their samples. The result will be a model for high throughput structure determination utilizing high-end instrumentation that can reveal the inner workings of complex macromolecules and subcellular structures.

Public Health Relevance

The Southeastern Consortium for Microscopy of MacroMolecular Machines (SECM4) comprises 15 Medical Centers and Universities using high-resolution cryogenic electron microscopy to study critical biomedical projects. Consortium members research disease pathogens including viruses such as HIV, polio, adenovirus, papilloma virus and measles virus; bacterial pathogens such Vibrio cholera, Salmonella typhimurium, Shigella sp., which cause dysentery. Others study proteins such as BRCA1, a causative agent of breast cancer and large enzymes such as Complex I, defects in which are linked to Parkinson's disease, to name only a few.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Wu, Mary Ann
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Florida State University
Schools of Arts and Sciences
United States
Zip Code
Jiang, Qiu-Xing (2018) Structural variability in the RLR-MAVS pathway and sensitive detection of viral RNAs. Med Chem :
Ilyas, Maria; Mietzsch, Mario; Kailasan, Shweta et al. (2018) Atomic Resolution Structures of Human Bufaviruses Determined by Cryo-Electron Microscopy. Viruses 10:
Dillard, Rebecca S; Hampton, Cheri M; Strauss, Joshua D et al. (2018) Biological Applications at the Cutting Edge of Cryo-Electron Microscopy. Microsc Microanal 24:406-419
Yadav, Gaya P; Zheng, Hui; Yang, Qing et al. (2018) Secretory granule protein chromogranin B (CHGB) forms an anion channel in membranes. Life Sci Alliance 1:e201800139
Mietzsch, Mario; Kailasan, Shweta; Garrison, Jamie et al. (2017) Structural Insights into Human Bocaparvoviruses. J Virol 91: