Cytoskeleton:It is now clear that the actin and microtubule cytoskeleton originated in bacteria. Our major research is on FtsZ, the bacterial tubulin homolog, which assembles into a contractile ring that divides the bacterium. We have studied FtsZ assembly in vitro, and found that it assembles into thin protofilaments. Dozens of these protofilaments are further clustered to form the contractile Z-ring in vivo. Recent discoveries include:
• The Z ring is very dynamic, exchanging subunits with a half time of 8 s.
• Reconstitution of Z rings in vitro. We provided FtsZ with a membrane tether, and found that when incorporated inside liposomes, membrane-targeted FtsZ can assemble Z rings without any other proteins.
• These reconstituted Z rings can also generate a constriction force on the membranes, again without any other proteins (no motor molecules).
• The constriction force is generated by a curved conformation of the protofilaments generating a bending force on the membrane.

Our long term goals are two-fold. First, to understand the mechanism of bacterial cell division. Second, to learn basic principles of assembly that will apply to both FtsZ and tubulin.

Extracellular Matrix: A second interest of our lab is extracellular matrix and cell adhesion, focusing now on fibronectin. We have discovered that the FN matrix is very elastic, with fibrils stretching up to four-fold over their relaxed length. We have two possible mechanisms to explain the elasticity of FN, and are currently developing experimental tests to resolve the mechanism. We are also studying the molecular structure of FN matrix fibrils and the mechanism of assembly. Assembly of "super FN" is providing important new insights.

Selected Publications
Complete publications, and some e-prints (pdfs)

Osawa, M., and H.P. Erickson. 2011. Inside-out Z rings - constriction with and without GTP hydrolysis. Molecular microbiology. 81:571-579.

Lemmon, C.A., T. Ohashi, and H.P. Erickson. 2011. Probing the folded state of fibronectin type-III domains in stretched fibrils by measuring buried cysteine accessibility. The Journal of biological chemistry.

Osawa, M., D.E. Anderson, and H.P. Erickson. 2008. Reconstitution of contractile FtsZ rings in liposomes. Science. 320:792-4.

Ohashi T, Galiacy SD, Briscoe G, Erickson HP. An experimental study of GFP-based FRET, with application to intrinsically unstructured proteins. Protein Sci 2007;16(7):1429-38.

Erickson HP. Evolution of the cytoskeleton. Bioessays 2007;29(7):668-677.

Chen Y, Erickson HP. Rapid in vitro assembly dynamics and subunit turnover of FtsZ demonstrated by fluorescence resonance energy transfer. J. Biol. Chem. 2005;280:22549-22554.

Anderson DE, Gueiros-Filho FJ, Erickson HP. Assembly Dynamics of FtsZ Rings in Bacillus subtilis and Escherichia coli and Effects of FtsZ-Regulating Proteins. J Bacteriol 2004;186(17):5775-81.

Erickson HP. Gene knockouts of c-src, TGF-beta1, and tenascin suggest superfluous, non-functional expression of proteins. Journal of Cell Biology 1993;120:1079-1081.

Current Projects and Lab Personnel

Tomoo Ohashi (Assistant Research Professor): Fibronectin matrix assembly and elasticity.

Masaki Osawa (Assistant Research Professor): FtsZ rings in liposomes - towards reconstituting cell division in vitro.

Sara Milam (Postdoc): Single molecule TIRF microscopy of FtsZ protofilament dynamics.

Kiani Arkus (Grad Student): The tail of FtsZ; finding suppressor mutations by Solexa sequencing.

Max Housman (Grad Student): Super-resolution light microscopy of FtsZ and fibronectin.

Desmond Moore (Biochemistry Grad Student): NMR of the FtsZ tail; search for insertions.

Riddhi Shah (Biochemistry Grad Student): Determining the protein-protein bonds in fibronectin matrix fibrils, using chemical crosslinking and mass spec.