Professor and Head
Department of Biology

Education and Training

A.B. Randolph-Macon Woman’s College, Lynchburg, VA
Chemistry

Ph.D. Dartmouth College
Cell Biology

Dr. Gilbert trained as a Postdoctoral Fellow with Dr. Kenneth Johnson at Pennsylvania State University, University Park, PA, and joined the faculty in the Department of Biological Sciences at the University of Pittsburgh in 1995.  Dr. Gilbert moved to Rensselaer in 2007.

She is a member of the American Society for Cell Biology, a member of Council and Chair of the Membership Committee for the Biophysical Society, Fellow and member of the Board of Directors for the American Academy of Nanomedicine as well as member of the American Association for the Advancement of Science, the American Chemical Society, and the American Society for Biochemistry and Molecular Biology.  She is on the editorial boards for the Biophysical Journal, Journal of Biological Chemistry, Nanomedicine, and Nanomedicine: Nanotechnology, Biology, and Medicine.

Contact

Office: Science Center Rm. 1W14

Rensselaer Polytechnic Institute
110 8th Street
Troy, NY 12180

Research Interests

Structure and mechanisms of microtubule-based molecular motors involved in cell motility and cytoskeletal dynamics.

Dr. Gilbert’s lab is interested in cellular movements, and the molecular motors that drive these movements. These remarkable nanoscale machines are involved in diverse biological processes ranging from neuronal development and axoplasmic transport to muscle contraction, meiosis, mitosis, cytokinesis, signal transduction as well as transport of membrane, messenger RNA, and proteins.  These molecular motors, regardless of their biological function, all have the ability to convert chemical energy into motion.  My research is directed at one family of biological motors, the kinesin superfamily, to ask how these enzymes, fueled by ATP turnover, interact with their microtubule track.  These kinesins can pull a cellular cargo along a microtubule, slide one microtubule relative to another, or even remodel the microtubule cytoskeleton by shortening or destabilizing the microtubules.  In addition, there are kinesins that actually lengthen the microtubules by adding on tubulin subunits to one end of the microtubule.  Yet, these kinesin motors are tiny—for example the catalytic engine is only a few nanometers in diameter. 

 Our experimental tools include rapid mixing instruments (chemical quench-flow and stopped-flow) that can mix reactants on the millisecond time scale to quantify individual chemical reaction steps that occur as kinesin interacts with the microtubule.  For a single event, the motor must attach to the microtubule, generate force through a series of structural transitions, and then detach from the microtubule for the next cycle.  Coupled to this mechanical cycle is a chemical cycle of ATP binding, ATP hydrolysis, and release of the products, ADP and inorganic phosphate (P_i).  Our research has revealed that variation in the coupling mechanism of ATP turnover to subtle differences in structure account for the remarkable specificity and diversity in kinesin-powered mechanical events.  The knowledge gained by this research is expected to be important in applications such as drug discovery and development, nanoscale devices, and regenerative medicine.

Current projects focus on several important kinesin motors, including the following: 

• Kinesin, an ATPase that drives axoplasmic vesicle movements to the synapse.
• Ncd, a Drosophila meiotic and mitotic spindle motor. 
• Kar3Cik1, the yeast microtubule depolymerase required for nuclear fusion during mating.
• Kar3Vik1, a budding yeast kinesin involved in mitotic spindle assembly and function.
• Eg5, a spindle motor essential for mitotic spindle assembly and function.

Selected Publications

Krzysiak, TC, M Grabe, and SP Gilbert (2008). Getting in sync with dimeric Eg5. Initiation and regulation of the processive run. J Biol Chem. 283, 2078-2087.

Allingham, JA, LR Sproul, I. Rayment, and SP Gilbert (2007).  Vik1 Modulates Microtubule-Kar3 Interactions Through a Motor Domain That Lacks an Active Site.  Cell 128, 1161-1172.

Sproul, LR, DJ Anderson, AT Mackey, WS Saunders, and SP Gilbert (2005).  Cik1 Targets the Minus- end Kinesin Depolymerase Kar3 to the Microtubule Plus-ends.  Curr. Biol. 15, 1420-1427.

Krzysiak, TC, and SP Gilbert (2006).  Dimeric Eg5 Maintains Processivity Through Alternating-site Catalysis with Rate-limiting ATP Hydrolysis.  J. Biol. Chem.  281, 39444-39454.

Krzysiak, TC, T Wendt, LR Sproul, P Tittman, H Gross, SP Gilbert, and A Hoenger (2006).  A Structural Model for Monastrol Inhibition of Dimeric Kinesin Eg5.  EMBO J.  25, 2263-2273.

Valentine, MT, PM Fordyce, TC Krzysiak, SP Gilbert, and SM Block (2006).  Individual Dimers of the Mitotic Kinesin Motor Eg5 Step Processively and Support Substantial Loads in vitro.  Nature Cell Biol. 8, 470-476.

Valentine, MT, and SP Gilbert (2007).  To Step or Not to Step?  How Biochemistry and Mechanics Influence Processivity in Kinesin and Eg5.  Curr. Opin. Cell Biol.  19, 75-81.

Cochran, JC, TC Krzysiak, and SP Gilbert (2006).  Pathway of ATP Hydrolysis by Monomeric Eg5.  Biochemistry 45, 12334-12344.

Cochran, JC, and SP Gilbert (2005).  ATPase Mechanism of Eg5 in the Absence of Microtubules: Insight into Microtubule Activation and Allosteric Inhibition by Monastrol.  Biochemistry  44,16633-16648.

Cochran, JC, JE Gatial III, TM Kapoor, and SP Gilbert (2005).  Monastrol Inhibition of the Mitotic Kinesin Eg5.  J Biol Chem 280, 12658-12667.

Cui, W, LR Sproul, SM Gustafson, HJG Matthies, SP Gilbert, and RS Hawley (2005). Drosophila Nod Protein Binds Preferentially to the Plus Ends of Microtubules and Promotes Microtubule Polymerization in vitro.  Mol Biol Cell  16, 5400-5409.

Klumpp, LM, A Hoenger, and SP Gilbert (2004).  Kinesin’s Second Step.  PNAS  101, 3444-3449.