The Southeastern Consortium for Microscopy of MacroMolecular Machines (SECM4) comprises 10 Universities/Medical Centers throughout the Eastern United States with a total of 13 cryoEM investigators studying a wide range of important biomedical problems as variable as high resolution virus structure, membrane protein structure, macromolecu- lar complexes of various types, some isolated in active form from cells, bacterial ultrastructure, spliceosomes, ribosome complexes all of which benefit from access to Florida State Universities (FSU) Titan Krios and its DE-64 direct electron detector. Recently the FSU Titan Krios was upgraded through the addition of a FEI Volta phase plate and a Gatan BioQuantum/K3 imaging filter which facilitate imaging of small molecules using single particle methods as well as thicker specimens that are imaged using cryoelectron tomography. The upgrades expanded the range of medically related structural biology problems to which SECM4 members can contribute. These upgrades also have made the FSU Titan Krios, which was one of the earliest ones installed in the US, comparable to recently installed Titan Krios microscopes, except for one feature. Newer Titan Krios microscopes have a more robust Autoloader than the early version currently operating on The FSU microscope. The Autoloader is the device that facilitates exchange of frozen hydrated specimens from the outside world into the high, contamination free environment of the Titan Krios. The current Autoloader, installed in August 2011, is currently responsible for more than 50% of the operational down time due to instrument failure. This Administrative Supplement seeks funds to replace the current Autoloader with the most recent version with the goal of reducing the greatest cause of instrument down time. SECM4 operates on the synchrotron template currently in use at sites having X-ray crystallography beam lines around the country. SECM4 members ship specimens to FSU and watch the data being collected as it comes off the microscope from the familiar confines of their own laboratories. SECM4 provides 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. SECM4 will become a model for high throughput structure determination utilizing high-end instrumentation to reveal the inner workings of complex macromolecules and subcellular structures.

Public Health Relevance

The Southeastern Consortium for Microscopy of MacroMolecular Machines (SECM4) comprises 10 Medical Centers and Universities using high-resolution cryogenic electron microscopy in studies of critical biomedical phenomena. Consortium members research disease pathogens including viruses such as HIV-1, Alphavirus, AdenoAssociated Virus (AAV), Respiratory Syncytial Virus (RSV), bacteria such as Staphylococcus aureus. Others projects are studying protein translation, muscle structures such as thin filaments, myosin catalytic intermediates, myosin binding protein-C, a factor in heart disease, exosomes for cancer treatment, RNAi, human telomere end-binding complex, CTFR, a protein involved in cystic fibrosis, to name but 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: