The Matthies lab is interested in the structure and function of membrane protein complexes in their native lipid membrane environment to understand their mechanism and the influence of the immediate surrounding in human health and disease. A cell contains many different lipid membranes with various lipid contents and distributions which are very important for a membrane’s morphology and function but very little is understood on how these various micro-environments are formed, maintained and how they influence the structure and function of membrane proteins. Studying membrane protein complexes in their native biological membrane is therefore required.
We use a combination of molecular biology, biochemistry and biophysical methods to study molecular transport across membranes with a focus on how the immediate native environment influences the structure and function of membrane proteins, but also how proteins and lipids shape and functionalize a lipid membrane.
Cryo-Electron Microscopy (Cryo-EM) is one of the main structural biology methods of the lab. We solve high-resolution structures of membrane proteins in artificial environments such as detergent micelles and lipid nano-discs using Single-Particle Cryo-EM, but we are extending this approach to studying membrane proteins in their native environment using native lipid nano-discs, membrane fractions in forms of vesicles, and intact cells and tissues using a combination of Correlative Light and Electron Microscopy techniques, including Cryo-Fluorescent Microscopy, Cryo-Focused Ion Beam-Scanning Electron Microscopy (Cryo-FIBSEM), Cryo-EM and Cryo-Electron Tomography (Cryo-ET).
Doreen Matthies is an Earl Stadtman tenure-track investigator and the Head of the Unit on Structural Biology in the Division of Basic and Translational Biophysics at NICHD. She obtained her diploma in Molecular Biology (2008) and her Ph.D. in Biochemistry (2014) from the University of Frankfurt in Germany while performing her research work in the group of Thomas Meier at the Max-Planck-Institute of Biophysics in the Department of Structural Biology lead by Werner Kühlbrandt. She joined the group of Sriram Subramaniam in the Laboratory of Cell Biology at NCI, NIH for her postdoctoral work (2013-2018) followed by two years in the Cryo-EM Department at HHMI Janelia before starting her own Structural Biology lab within NICHD at the end of 2020.
- Petersen JD, Lu J, Fitzgerald W, Zhou F, Blank PS, Matthies D, Zimmerberg J. Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein. Viruses. 2022;14(5).
- Nguyen C, Lei HT, Lai LTF, Gallenito MJ, Mu X, Matthies D, Gonen T. Lipid flipping in the omega-3 fatty-acid transporter. Nat Commun. 2023;14(1):2571.
- Qiu B, Matthies D, Fortea E, Yu Z, Boudker O. Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport. Sci Adv. 2021;7(10).
- Matthies D, Bae C, Toombes GE, Fox T, Bartesaghi A, Subramaniam S, Swartz KJ. Single-particle cryo-EM structure of a voltage-activated potassium channel in lipid nanodiscs. Elife. 2018;7.
- Matthies D, Dalmas O, Borgnia MJ, Dominik PK, Merk A, Rao P, Reddy BG, Islam S, Bartesaghi A, Perozo E, Subramaniam S. Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating. Cell. 2016;164(4):747-56.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Biomedical Engineering and Biophysics
This page was last updated on Monday, November 13, 2023