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Michael Marko

Michael Marko

Cellular and Molecular Basis of Diseases - Manager of the 3D-EM Facility
Adjunct Professor, College of Nanoscale Science and Engineering, SUNY Poly

Research Interests

As one of the founding members of our electron microscopy development lab, I have been working on advancing biological transmission electron microscopy (TEM) technology since 1976, and have been involved in several US or worldwide “firsts”. Examples are: stereoscopic 3-D image analysis; cryo-TEM tomography of native frozen tissue; use of cryo ion-milling to prepare frozen tissue and cells for cryo-TEM; phase-plate imaging for cryo-TEM.

I currently lead two NIH-funded research projects: (1) use of cryo-focused-ion-beam (FIB) milling to prepare vitreously frozen specimens for high-resolution cryo-TEM, and (2) use of phase-plate imaging to improve contrast of vitreously frozen specimens in the cryo-TEM. These are represented in the image to the left. (A) Scanning electron microscope (SEM) image of the surface of a block of native (frozen, unstained) muscle in which cryo-FIB milling was used to thin rectangular strips for cryo-TEM imaging. (B) cryo-TEM image from a thinned area in A. This is an example of the first cryo-TEM images recorded of native, frozen muscle; however it was recorded with a conventional high-defocus method. Such a method enhances contrast but results in complete loss of certain information. (C) TEM image of a frozen liver slice recorded in-focus, which in principle does not result in complete information loss, but the image has insufficient contrast for analysis. (D) TEM image of the same specimen recorded in-focus, but using a phase plate to enhance contrast without loss of information.

I am also manager of Wadsworth Center’s 3D-EM Facility, which includes several high-end electron microscopes, including a FIB-SEM (both FIB and SEM instruments combined in a single platform) and a new custom-made 300-kV phase-plate cryo-TEM. The Facility is available for use by both Wadsworth and external investigators.

Select Publications

Kishchenko G, Danev D, Fisher R, He J, Hsieh C, Marko M, Sui H.
Effect of fringe-artifact correction on sub-tomogram averaging from Zernike phase-plate cryo-TEM.
Journal of Structural Biology.
Hsieh C, Schmelzer T, Kishchenko G, Wagenknecht T, Marko M.
Practical workflow for cryo focused-ion-beam milling of tissues and cells for cryo-TEM tomography.
J Struct Biol.
Marko M, Meng X, Hsieh C, Roussie J, Striemer C.
Methods for testing Zernike phase plates and a report on silicon-based phase plates with reduced charging and improved ageing characteristics.
J Struct Biol.
Marko M, Leith A, Hsieh C, Danev R.
Retrofit implementation of Zernike phase plate imaging for cryo-TEM.
Journal of Structural Biology.
Marko M, Hsieh C, Schalek R, Frank J, Mannella C.
Focused-ion-beam thinning of frozen-hydrated biological specimens for cryo-electron microscopy.
Nat Methods.
Marko M, Hsieh C, Moberlychan W, Mannella CA, Frank J.
Focused ion beam milling of vitreous water: prospects for an alternative to cryo-ultramicrotomy of frozen-hydrated biological samples.
J Microsc.
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