Cells utilize dynamic biopolymer networks to carry out mechanical tasks during diverse processes such as cell division, migration, and development. Disruptions in the integrity of these networks have been linked to disease, and chemical compounds (e.g. taxol, the vinca alkaloids) that target biopolymers such as microtubules have been used extensively as therapeutics in the treatment of cancer. Single molecule biophysical studies of proteins and DNA have yielded insights into the function of individual components required for these processes. However, intracellular networks are organized on the micron-scale by the collective action of ensembles of dozens of such proteins. It is currently unclear how long-range mechanical cues are transmitted or how diverse nanometer-scale ‘building blocks’ are organized within the micron-scale structures that do work in cells.
The Forth lab combines biophysical techniques, such as optical trapping and total internal reflection fluorescence microscopy, to understand how forces are transmitted across these networks. By reconstituting functionally active microtubule networks out of purified components and monitoring how the system behaves under biologically relevant mechanical constraints, we seek to elucidate the mechanisms that drive successful cell division.
Dr. Forth received his Ph.D. in physics from Cornell University in 2009, where his doctoral work involved designing next-generation optical trapping instruments and monitoring the response of DNA to twisting and stretching. Dr. Forth then pursued post-doctoral research in the Laboratory of Chemistry and Cell Biology at the Rockefeller University in New York City, where he focused on applying biophysical methods to the study of microtubule networks that are used by cells during cell division. Dr. Forth joined the faculty of the Department of Biological Sciences at Rensselaer Polytechnic Institute as an Assistant Professor in August of 2016.
- I. Gaska, A. Alfieri, M. Armstrong, and S. Forth The mitotic crosslinking protein PRC1 is a viscous dashpot against microtubule sliding https://www.biorxiv.org/content/10.1101/2019.12.12.874529v1 (2020).
- T. Bodrug, E. Wilson-Kubalek, S. Nithianantham, A. Thompson, A. Alfieri, I. Gaska, J. Major, G. Debs, S. Inagaki, P. Gutierrez, L. Gheber, R. McKenney, C. Sindelar, R. Milligan, J. Stumpff, S. Rosenfeld, S. Forth, J. Al-Bassam The Kinesin-5 Tail Domain Directly Modulates the Mechanochemical Cycle of the Motor for Anti-Parallel Microtubule Sliding eLife 2020;9:e51131 (2020).
- M. C. Pamula, L. Carlini, S. Forth, P. Verma, S. Suresh, W. Legant, A. Khodjakov, E. Betzig, and T. M. Kapoor High-resolution imaging reveals how the spindle midzone impacts chromosome movement Journal of Cell Biology 218(8), 2529-2544 (2019).
- S. Forth, T.M. Kapoor. The mechanics of microtubule networks in cell division. Journal of Cell Biology 216, 1525-31 (2017).
- Y. Shimamoto*, S. Forth*, T.M. Kapoor (*co-first authors). Measuring pushing and braking forces generated by ensembles of kinesin-5 crosslinking two microtubules. Developmental Cell 34, 669-681 (2015).
- S. Forth, K.-C. Hsia, Y. Shimamoto, T.M. Kapoor. Asymmetric friction of non-motor MAPs can lead to their directional motion in active microtubule networks. Cell 157, 420-32 (2014).
- S.-C. Ti, M.C. Pamula, S.C. Howes, C. Duellberg, N.I. Cade, R.E. Kleiner, S. Forth, T. Surrey, E. Nogales and T.M. Kapoor. Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends. Developmental Cell 37, 72-84 (2016).
- K.-C. Hsia, E.M. Wilson-Kubalek, A. Dottore, Q. Hao, K.-L. Tsai, S. Forth, Y. Shimamoto, R.A. Milligan, and T.M. Kapoor. Reconstitution of the augmin complex provides insights into its architecture and function. Nature Cell Biology 16, 852-863 (2014).
- S. Forth, C. Deufel, M.Y. Shienin, B. Daniels, J.P. Sethna and M.D. Wang. Abrupt Buckling Transition Observed during the Plectoneme Formation of Individual DNA Molecules. Physical Review Letters 100:148301 (2008).
- J. Inman*, S. Forth*, and M.D. Wang (*contributed equally to this work). Passive Torque Wrench and Angular Position Detection Using a Single Beam Optical Trap. Optics Letters 35:17, 2949-51 (2010).
- M. Li, A. Hada, P. Sen, L. Olufemi, M.A. Hall, B.Y. Smith, S. Forth, J.N. McKnight, A. Patel, G.D. Bowman, B. Bartholomew, M.D. Wang. Dynamic regulation of transcription factors by nucleosome remodeling. eLife 2015;4:e06249 (2015).
- S. Forth, M.Y. Sheinin, J.T. Inman, and M.D. Wang. Torque Measurement at the Single Molecule Level. Annual Review of Biophysics 42, 583-604 (2013).
- S. Forth and M.D. Wang. Angular Optical Trapping. Encyclopedia of Biophysics, Springer Reference, (2012).
- M. Sheinin, S. Forth, J.F. Marko, and M.D. Wang. Underwound DNA under Tension: Structure, Elasticity, and Sequence-Dependent Behaviors. Physical Review Letters 107:108102 (2011).
- S. Forth, C. Deufel, S.S. Patel, M.D. Wang. Direct Measurements of Torque during Holliday Junction Migration. Biophysical Journal 100, L05-L07 (2011).
- C. Deufel, S. Forth, C.R. Simmons, S. Dejgosha and M.D. Wang. Nanofabricated quartz cylinders for angular optical trapping: torque detection during DNA supercoiling. Nature Methods 4, 223-5 (2007).
- B. Daniels, S. Forth, M.Y. Sheinin, M.D. Wang and J.P. Sethna. Discontinuities at the DNA Supercoiling Transition. Physical Review E 80:040901 (2009).