de Pablo Group

Joshua Lequieu

  • Graduate Student

  • Contact: lequieu@uchicago.edu
    773.834.2912
  • Office Location:
    Searle Laboratory 105
    5735 South Ellis Avenue
    Chicago, IL 60637

Joshua Lequieu was born in San Jose, California and grew up in the nearby town of Cupertino (a town most often known as the home of Apple). He received his BS in chemical engineering from Cornell University in 2010. Joshua stayed at Cornell an additional year and received an MS in chemical engineering in 2011 under the direction of Professor Jeffrey Varner. After starting a PhD at UW-Madison, Joshua Lequieu moved to UChicago (and the Pritzker School of Molecular Engineering) in 2013 to continue his research with Professor de Pablo.

In addition to molecular modeling, Joshua enjoys listening to and playing music, spending time over good food with good friends, good film, cycling, and sailing when the weather permits. He also enjoys reading and discussing a broad range of topics outside the scope of his research.

The ability to engineer the self-assembly of nano-scale objects to create highly ordered materials is of considerable scientific and practical interest. This new class of materials represents a powerful approach for engineering the next generation of devices whose mechanical, optical, and electrical properties can be precisely tuned at the molecular scale. Though significant strides toward this goal have been achieved in recent years, the complexity achieved in engineered systems is still far surpassed by that achieved by nature. Precise self-assembly is achieved by nature through proteins and nucleic acids that fold into intricate, three-dimensional, and importantly, functional structures. A promising avenue toward improved engineered systems is to draw on discoveries from biophysics in order to inspire new approaches and paradigms for self-assembly and materials design. In Joshua's research, he explores the interplay between biophysics and engineering by exploring the self-assembly of DNA.

Joshua's PhD research began at the smallest length scales of DNA, first by understanding the hybridization of DNA, and then how hybridization can be used in materials to direct the self-assembly of gold nanoparticles. He presented the first evidence of a tunable mechanical response in these assemblies, thereby suggesting the possibility of mechanical meta-materials constructed using DNA. His research then proceeded to larger length scales, where he examined the biophysical processes that control the compaction of DNA into chromatin. Using a detailed molecular model, he explored the free energies and dynamics of the smallest building block of chromatin, a protein-DNA complex called the nucleosome. These results are in quantitative agreement with existing experimental measurements, and help to explain the molecular factors that dictate the first stages of DNA compaction into chromatin. Lastly, he designed a multi-scale approach that can couple information across different length scales of chromatin in order to examine the folding of large regions of DNA. By drawing on both the biophysics and engineering literature, his research suggests new approaches for materials design and offers new paradigms for synthetic systems that seek to mimic the complexity achieved by nature.

1CPN: A coarse-grained multi-scale model of chromatin

Lequieu, Joshua, et al. "1CPN: A coarse-grained multi-scale model of chromatin." The Journal of chemical physics 150.21 (2019): 215102.

Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning

Guo, Ashley Z., Joshua Lequieu, and Juan J. de Pablo. "Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning." The Journal of chemical physics 150.5 (2019): 054902.

The Free Energy Landscape of Internucleosome Interactions and Its Relation to Chromatin Fiber Structure

Moller, Joshua, Joshua Lequieu, and Juan J. de Pablo. "The Free Energy Landscape of Internucleosome Interactions and Its Relation to Chromatin Fiber Structure." ACS central science 5.2 (2019): 341-348.

Ssages: Software suite for advanced general ensemble simulations

Sidky, Hythem, et al. "Ssages: Software suite for advanced general ensemble simulations." The Journal of chemical physics 148.4 (2018): 044104.

In silico evidence for sequence-dependent nucleosome sliding

Lequieu, Joshua, David C. Schwartz, and Juan J. de Pablo. "In silico evidence for sequence-dependent nucleosome sliding." Proceedings of the National Academy of Sciences 114.44 (2017): E9197-E9205.

A molecular view of the dynamics of dsDNA packing inside viral capsids in the presence of ions

Córdoba, Andrés, et al. "A molecular view of the dynamics of dsDNA packing inside viral capsids in the presence of ions." Biophysical journal 112.7 (2017): 1302-1315.

Tension-dependent free energies of nucleosome unwrapping

Lequieu, Joshua, et al. "Tension-dependent free energies of nucleosome unwrapping." ACS central science 2.9 (2016): 660-666.

Mechanical response of dna–nanoparticle crystals to controlled deformation

Lequieu, Joshua, et al. "Mechanical response of dna–nanoparticle crystals to controlled deformation." ACS central science 2.9 (2016): 614-620.

A molecular view of DNA-conjugated nanoparticle association energies

Lequieu, Joshua P., Daniel M. Hinckley, and Juan J. de Pablo. "A molecular view of DNA-conjugated nanoparticle association energies." Soft Matter 11.10 (2015): 1919-1929.

Coarse-grained modeling of DNA curvature

G. S. Freeman, D. M. Hinckley, J. P. Lequieu, J. K. Whitmer, and J. J. de Pablo. Coarse-grained modeling of DNA curvature. JCP. 2014. Vol. 141, Pg. 165103.

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