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Narendra Maheshri, Ph.D.

Department Chemical Engineering
Assistant Professor of Chemical Engineering

Room 66-558
617-258.8986 (phone)

Biosketch

S.B. Chemical Engineering, MIT 1999
S.B. Biology, MIT, 1999
Ph.D. Chemical Engineering, UC Berkeley, 2004
Postdoc, UCSF / Harvard, 2005-2006

Research Summary

My lab conducts fundamental studies aimed at understanding the in vivo dynamics of eukaryotic gene expression and regulation using budding yeast as a model organism. Our current focus is to describe how complex dynamical behaviors (delays, noise filtering/production, memory, feedback control) typically attributed to gene networks can actually be encoded at the level of a single gene. By combining biophysical and kinetic modeling with experimental genetics, molecular biology, and microscopy, the work broadly aims to define (natural) and design (synthetic) “pathways” at promoters that lead to particular gene expression dynamics. We are also interested in exploring the ability of a “bottom-up” approach to describe the dynamics of gene regulatory networks containing these promoters.

A second area of interest is to translate our fundamental studies into techniques to generate phenotypic diversity within a population of cells. Just as in protein engineering, metabolic engineering and synthetic biology can benefit from both rational and random, combinatorial approaches to yielding a desired trait. We are developing experimental approaches to modulating/mutating groups of genes in a rapid and scalable manner that should aid in the realizing a desirable multigenic phenotype.

Selected Publications

  • Maheshri N., Koerber J. T., Kaspar B.K. and Schaffer D.V. “Directed evolution of adeno-associated virus yields enhanced gene delivery vectors.” Nat Biotechnol 24. 198-204, February 2006.
  • Bar-Even A., Paulsson J., Maheshri N., O'Shea E.K., Pilpel Y. and Barkai N. “Noise in gene expression scales with natural protein abundance.” Nat Genetics 38. 636-43, June 2006.
  • Maheshri N. and O’Shea E.K. ““Living with noisy genes: how cells function reliably with inherent variability in gene expression.” Ann Rev Biophys Biomol Struct 36. 413-34, 2007.
  • Octavio L.M., Gedeon K., and Maheshri N. “Epigenetic and conventional regulation is distributed among activators of FLO11 allowing tuning of population-level heterogeneity in its expression.” PLoS Genet. 5. e1000673, October 2009.
  • To T.L. and Maheshri N. “Noise induces bimodality in transcriptional positive feedback loops without bistability.” Science. 372. 1142-5, February 2010.

Last Updated: August 5, 2010