Ben O’Shaughnessy

PROFESSOR OF CHEMICAL ENGINEERING

824 S.W. Mudd
Mail Code 4721

Tel(212) 854-3203
Fax(212) 854-3054

Ben O’Shaughnessy studies the mechanisms used by living cells for vital functions in health and disease. Combining computational modeling and experiment, he studies neurotransmission in the brain. Cognition and coordinated motor activity rely on tightly controlled release of neurotransmitters at synapses where neurons meet in the complex network that constitutes the brain. O’Shaughnessy seeks to understand these synaptic release processes: how they are triggered with exquisite synchrony in the healthy brain, and how they become altered in neurodegenerative disorders such as Alzheimer’s or neurodevelopmental disorders such as epilepsy. 

Research Interests

Neurotransmission, hormone secretion, mechanics of cell division, actomyosin contractility, cellular cytoskeleton, cell migration, viral infection

Another major research area is cell division. He aims to understand the mechanisms that cells use to divide themselves, a process vital to life as it enables growth and maintenance of an individual and propagation of its genetic identity. Cell division is fundamental to cancer, where division becomes misregulated. O’Shaughnessy seeks to understand how cells build and operate remarkable multi-component machines that exert sufficient force to constrict and cleave the cell into two, and how positioning, assembly and constriction of these machines is misregulated in cancer. Other research addresses mechanisms of infection by enveloped viruses such as influenza, HIV and ebola; secretion of hormones, which control functions of organs and cells in the body; cell migration; and force production and mechanosensitivity in the cell’s actomyosin cytoskeleton.

O’Shaughnessy’s research typically involves tight collaborations with experimental bioengineers and biologists, where quantitative analysis, cell biology, and engineering coordinate to unravel the workings of complex cellular machinery. Modeling is typically multiscale. O’Shaughnessy developed molecularly explicit but highly coarse-grained computational models of the membrane fusion machinery at neuronal synapses. These models explain how action potentials trigger synchronized fusion of synaptic vesicles with the neuronal plasma membrane, and hence neurotransmitter release on sub-millisecond timescales. Atomistic computations are used to quantify key properties of fusion machinery proteins (SNAREs, synaptotagmin, complexin) needed by the coarse-grained approaches. O’Shaughnessy and his graduate students have developed the most advanced computer simulation of the actomyosin contractile ring used by cells to divide themselves into two.  Simulations and analytical models explain how the ring exerts force, constricts, and combats instabilities inherent to contractile actomyosin structures. O’Shaughnessy developed the first experimental method to measure the tension of the contractile ring, the fundamental property whereby it exerts force.

O’Shaughnessy received a BSc in mathematics and physics from Bristol University in 1977, and his PhD in physics from Cambridge University in 1984, in the area of theoretical polymer physics. During his postdoctoral fellowship at the Weizmann Institute of Science, 1983-86, he studied non-linear dynamics and chaos. 

RESEARCH EXPERIENCE

  • Associate research scientist, Departments of Applied Physics and Chemical Engineering, Columbia University, 1987
  • Postdoctoral fellow, Weizmann Institute of Science, 1983-1986

PROFESSIONAL EXPERIENCE

  • Professor of chemical engineering, Columbia University, 2003-
  • Associate professor of chemical engineering, Columbia University, 1994–2003
  • Assistant professor of chemical engineering, Columbia University, 1988–1994
  • British Petroleum Company, Sunbury-on-Thames, 1977-1980
 

PROFESSIONAL AFFILIATIONS

  • Biophysical Society
  • American Society of Cell Biology 

 

 

SELECTED PUBLICATIONS

  • H. Mostafavi, S. Thiyagarajan, B. S. Stratton, E. Karatekin, J. M. Warner, J. E. Rothman and B. O'Shaughnessy. "Entropic forces drive self-organization and membrane fusion by SNARE proteins.” Proc. Natl. Acad. Sci. USA, 114, 5455–5460 (2017).
  • Wu, Z., O. D. Bello, S. Thiyagarajan, S. M. Auclair, W. Vennekate, S. S. Krishnakumar, B. O'Shaughnessy and E. Karatekin. “Dilation of fusion pores by crowding of SNARE proteins.” eLife, 10.7554/eLife.22964, 2017.
  • B. S. Stratton, J. M. Warner, Z. Wu, G. Wei, E. Wagnon, D. Baddeley, E. Karatekin and B. O'Shaughnessy, “Cholesterol increases the openness of SNARE-mediated flickering fusion pores,” Biophysical Journal, 110, 1538–1550 (2016). 
  • H. Wolfenson, G. Meacci, S. Liu, M. R. Stachowiak, T. Iskratsch, S. Ghassemi, P. Roca-Cusachs, B. O’Shaughnessy, J. Hone and M. P. Sheetz, “Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices,” Nat. Cell Biol. 18, 33–42 (2016).
  • Thiyagarajan, S., Munteanu, E. L., Arasada, R., Pollard, T. D. & O’Shaughnessy, B. “The Fission Yeast Cytokinetic Contractile Ring Regulates Septum Shape and Closure.” J. Cell Sci. 128, 3672–3681 (2015).
  • M. R. Stachowiak, M. A. Smith, E. Blankman, L. Luettjohann, H. E. Balcioglu, M. C. Beckerle, and B. O’Shaughnessy, “A Mechanical-Biochemical Feedback Loop Regulates Remodeling in the Actin Cytoskeleton”, Proc. Natl. Acad. Sci. USA, 2014, 111, 17528-17533. 
  • M. R. Stachowiak, C.  Laplante, H. F. Chin, B. Guirao, E.  Karatekin, T. D. Pollard, and B. O'Shaughnessy. "Mechanism of Cytokinetic Contractile Ring Constriction in Fission Yeast," Dev. Cell, 2014, 29, 547-561. 
  • J.M. Warner and B. O’Shaughnessy, “The hemifused state on the pathway to membrane fusion”, Phys. Rev. Lett. 108, 178101 (2012).
  • E. Karatekin, J. di Giovanni, C. Iborra, J. Coleman, B. O’Shaughnessy, M. Seagar, and J. E. Rothman, “A fast, single-vesicle fusion assay mimics physiological SNARE requirements”, Proc. Natl. Acad. Sci. USA 107, 3517–3521 (2010).
  • D. Vavylonis, J.-Q. Wu, S. Hao, B. O’Shaughnessy, and T. D. Pollard, “Assembly Mechanism of the Contractile Ring for Cytokinesis by Fission Yeast”, Science 319, 97-100 (2008).