Cells use networks of interacting regulatory molecules to process information, make memories, and execute computations. Our research is interested in the design, function, and evolution of these cellular regulatory systems. To examine them, we employ multidisciplinary approaches including synthetic biology, which allows us to construct artificial versions of these regulatory systems from components “parts” to systematically explore their design principles and functional properties. Our work has pioneered synthetic biology platforms for engineering a wide range of cellular systems, from eukaryotic transcriptional networks to chromatin/epigenetic regulation and functional protein aggregation systems. In parallel, we invent high-throughput technologies, such as the eVOLVER system for continuous cell growth, to help us experimentally interrogate cellular adaptation and to conduct continuous laboratory evolution of regulatory molecules and cells. Ultimately, with these tools and approaches, we aim to gain integrated, quantitative understanding of how cellular decisions and phenotypes emerge from underlying regulatory networks, and how these phenotypes are adapted to evolutionary selective pressures. We additionally seek to translate our synthetic tools to address unmet biomedical and therapeutic needs, such as development of gene expression control schemes for gene- and cell-based therapy, and cell-based models and platforms for neurodegenerative disease.

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Engineering Epigenetic Regulation Using Synthetic Read-Write Modules
Minhee Park, Nikit Patel, Albert J. Keung and Ahmad S. Khalil
Cell, 176: 227-238 (2019)

Modeling the Impact of Drug Interactions on Therapeutic Selectivity
Zohar B. Weinstein, Nurdan Kuru, Szilvia Kiriakov, Adam C. Palmer, Ahmad S. Khalil, Paul A. Clemons, Muhammad H. Zaman, Frederick P. Roth and Murat Cokol
Nature Communications, 9: 3452 (2018)

Precise, Automated Control of Conditions for High-Throughput Growth of Yeast and Bacteria with eVOLVER
Brandon G. Wong*, Christopher P. Mancuso*, Szilvia Kiriakov, Caleb J. Bashor and Ahmad S. Khalil
Nature Biotechnology, 36: 614-623 (2018)

Hsf1 Phosphorylation Generates Cell-to-Cell Variation in Hsp90 Levels and Promotes Phenotypic Plasticity
Xu Zheng*, Ali Beyzavi*, Joanna Krakowiak, Nikit Patel, Ahmad S. Khalil and David Pincus
Cell Reports, 22: 3099-3106 (2018)

Hsf1 and Hsp70 Constitute a Two-Component Feedback Loop that Regulates the Yeast Heat Shock Response
Joanna Krakowiak*, Xu Zheng*, Nikit Patel*, Zoe A. Feder, Jayamani Anandhakumar, Kendra Valerius, David S. Gross, Ahmad S. Khalil and David Pincus
eLife, 7: e31668 (2018)

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