Ethan C. Garner
Department of Molecular and Cellular Biology
Center for Systems Biology
My group works to understand how cells create long range order: How enzymes, each acting at the nanometer scale, work together to build micron-sized cells of defined shapes. Our expertise involves combining quantitative microscopy with cell biology and genetics with to dissect the mechanisms by which bacteria grow and divide. We use ensemble and single molecule imaging to gain “dynamic signatures” for the active state of each protein, allowing us to: 1) quantify their activity, 2) observe how they respond to different stresses and inputs, and 3) see how their dynamics change as we disrupt other factors. By combining systematic labeling of each component with chemical and genetic perturbations, we work to deconvolute the internal associations, regulation, and overall function of each process.
Primarly, we study cell shape determination in the gram-positive bacterium Bacillus subtilis, whose shape is conferred by its peptidoglycan sacculus, a multilayered, cross-linked meshwork surrounding the cell. This meshwork is grown via the addition of new strands at the membrane surface. The polymerization, crosslinking, and breakdown of glycans requires multiple enzymatic activities. While the identity and biochemical activity of most of these enzymes are known, how their nanometer scale activities are spatially regulated to allow bacteria to A) grow as rods of defined width, or B) divide in half is not understood. While the exact mechanism remains unclear, these enzymes are thought to be spatially regulated by cytoskeletal filaments: Rod-shaped growth by MreB (an actin homolog), and cell division by FtsZ (a tubulin) and FtsA (an actin).
My group has made several advances into the mechanisms mediating rod-shaped growth and division. We have elucidated: 1) which enzymes interact with these cytoskeletal filaments, 2) how their interactions with filaments (or lack thereof) affect their dynamics and activity, and 3) how filaments and their cellular localization affect the overall process. Our current and future work is focused on understanding how the cell coordinates the activity of these two systems with other essential in the cell processes.
We are now examining the internal cell biology of an unexplored domain of life, archaea. Biology has evolved many different ways to encode long-range order. By studying the diversity of mechanisms underlying shape formation, we hope to extract common rules of self-organization. Rather than a cell well, archaea use a tightly packed array of proteins called the S-Layer to maintain their shape. How they add material into this array while maintaining shape is not understood, nor how cytoskeletal filaments regulate this process. Using Halobacterium salinarum and Haloferax volcanni as model systems, we are examining archaea define their shapes, grow and divide. To do this, we are developing tools to adapt live cell microscopy and single molecule imaging to these organisms.
Hussain S, Wivagg CN, Szwedziak P, Wong F, Schaefer K, Izoré T, Renner LD, Holmes MJ, Sun Y, Bisson-Filho AW, Walker S, Amir A, Lowe J, Garner EC*. MreB filaments align along greatest principal membrane curvature to orient cell wall synthesis. Elife. 2018 Feb 22;7:1239.
Eun Y-J, Ho P-Y, Kim M, LaRussa S, Robert L, Renner LD, Schmid A*, Garner E*, Amir A*. Archaeal cells share common size control with bacteria despite noisier growth and division. Nat Microbiol. 2018 Feb;3(2):148-54.
Bisson-Filho AW, Hsu Y-P, Squyres GR, Kuru E, Wu F, Jukes C, Sun Y, Dekker C*, Holden S*, VanNieuwenhze MS*, Brun YV*, Garner EC*. Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science. 2017 Feb 17;355(6326):739-43.Garner EC, Bernard R, Wang W, Zhuang X, Rudner DZ, Mitchison T. Coupled, Circumferential Motions of the Cell Wall Synthesis Machinery and MreB Filaments in B. subtilis. Science, 2011 Jul 8;333(6039) p. 222-5. PMCID: PMC3235694.
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