The unifying theme of my group is dissecting the self-organizing mechanisms that create and read out long-range shape: how small collections of molecules build defined shapes 1000 times their size. Specifically, we study mechanisms of the spatial control of growth and division in bacteria and archaea as they accomplish these feats using minimal numbers of proteins. These minimal systems allow us to rapidly assay the functions and regulation of each component in vivo, then work toward rebuilding each system in vitro so we can dissect the underlying mechanisms driving their emergent function.
A diverse group, we study self-organization across a range of organisms and scales: from how various bacteria and archaea segregate their DNA, divide in two, and grow in different shapes, to the kinetics and functions of divergent cytoskeletal polymers that regulate and control these processes. One subset of our work aims to build thorough, mechanistic understandings of the systems underlying growth, rod shape formation, and cell division. We recently have begun working to understand the mechanics of these systems exert force on the cell to divide it in half, and, conversely, how these filaments and enzymes are regulated by forces within the cell envelope. Another focus is working to take a broad, genome-wide, systems-level effort to understand how the cell coordinates all its biosynthetic processes to scale with its rate of growth and division.
For this, we use genetics, biochemistry, and biophysical approaches. We often use microscopy to gain ensemble and single-molecule imaging to determine each protein’s “active dynamics”, a motion or diffusion constant only present when the protein is active or bound to others. Once we characterize the active dynamics of each protein, we then perturb every protein in the system, as well as others outside it, to determine which proteins change the dynamics of others. Done systematically, this approach gives insight into which proteins act as complexes, which are dependent on others. Overall, these approaches allow us to determine how that system both functions and is regulated, as well as how it interfaces with other cellular processes.
Stork DA; Squyres GR; Kuru E; Gromek KA; Rittichier J; Jog A; Burton BM; Church GM; Garner EC; Kunjapur AM, 2021. Designing efficient genetic code expansion in Bacillus subtilis to gain biological insights. Nat Commun 12(1):5429
Garner EC, 2021. Toward a Mechanistic Understanding of Bacterial Rod Shape Formation and Regulation. Annu Rev Cell Dev Biol 37:1-21
Squyres GR; Holmes MJ; Barger SR; Pennycook BR; Ryan J; Yan VT; Garner EC, 2021. Single-molecule imaging reveals that Z-ring condensation is essential for cell division in Bacillus subtilis. Nat Microbiol 6(5):553-562
Stoddard PR; Lynch EM; Farrell DP; Dosey AM; DiMaio F; Williams TA; Kollman JM; Murray AW; Garner EC, 2020. Polymerization in the actin ATPase clan regulates hexokinase activity in yeast. Science 367(6481):1039-1042
Bagamery LE; Justman QA; Garner EC; Murray AW, 2020. A Putative Bet-Hedging Strategy Buffers Budding Yeast against Environmental Instability. Curr Biol 30(23):4563-4578.e4
Dion MF; Kapoor M; Sun Y; Wilson S; Ryan J; Vigouroux A; van Teeffelen S; Oldenbourg R; Garner EC, 2019. Bacillus subtilis cell diameter is determined by the opposing actions of two distinct cell wall synthetic systems. Nat Microbiol 4(8):1294-1305
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; Löwe J; Garner EC, 2018. MreB filaments align along greatest principal membrane curvature to orient cell wall synthesis. Elife 7.
Bisson-Filho AW; Hsu YP; Squyres GR; Kuru E; Wu F; Jukes C; Sun Y; Dekker C; Holden S; VanNieuwenhze MS; Brun YV; Garner EC, 2017. Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science 355(6326):739-743
Cho H; Wivagg CN; Kapoor M; Barry Z; Rohs PDA; Suh H; Marto JA; Garner EC*; Bernhardt TG*, 2016. Bacterial cell wall biogenesis is mediated by SEDS and PBP polymerase families functioning semi-autonomously. Nat Microbiol 1:16172
Garner EC; Bernard R; Wang W; Zhuang X; Rudner DZ; Mitchison T, 2011. Coupled, circumferential motions of the cell wall synthesis machinery and MreB filaments in B. subtilis. Science 333(6039):222-5
Garner EC; Campbell CS; Weibel DB; Mullins RD, 2007. Reconstitution of DNA segregation driven by assembly of a prokaryotic actin homolog. Science 315(5816):1270-4
Garner EC; Campbell CS; Mullins RD, 2004. Dynamic instability in a DNA-segregating prokaryotic actin homolog. Science 306(5698):1021-5
A.Keith Dunker, J.David Lawson, Celeste J Brown, Ryan M Williams, Pedro Romero, Jeong S Oh, Christopher J Oldfield, Andrew M Campen, Catherine M Ratliff, Kerry W Hipps, Juan Ausio, Mark S Nissen, Raymond Reeves, ChulHee Kang, Charles R Kissinger, Robert W Bailey, Michael D Griswold, Wah Chiu, Ethan C Garner, Zoran Obradovic. 2001. Intrinsically disordered protein, Journal of Molecular Graphics and Modelling 19(26-59)
Romero P; Obradovic Z; Li X; Garner EC; Brown CJ; Dunker AK, 2001. Sequence complexity of disordered protein. Proteins 42(1):38-48
Li X; Obradovic Z; Brown CJ; Garner EC; Dunker AK, 2000. Comparing predictors of disordered protein. Genome Inform Ser Workshop Genome Inform 11:172-84
Dunker AK; Obradovic Z; Romero P; Garner EC; Brown CJ, 2000. Intrinsic protein disorder in complete genomes. Genome Inform Ser Workshop Genome Inform 11:161-71
Garner, E., P. Romero, A.K. Dunker, C. Brown, and Z. Obradovic, Predicting Binding Regions within Disordered Proteins. Genome Inform Ser Workshop Genome Inform, 1999. 10: p. 41-50.
Garner, E., P. Cannon, P. Romero, Z. Obradovic, and A.K. Dunker, Predicting Disordered Regions from Amino Acid Sequence: Common Themes Despite Differing Structural Characterization. Genome Inform Ser Workshop Genome Inform, 1998. 9: p. 201-213.