Cells use networks of interacting molecules to process information, make memories, and execute computations. We are broadly interested in the design and function of these cellular regulatory systems. To examine them, we primarily develop synthetic biology approaches, which allow us to construct artificial versions of these regulatory systems from components “parts” and systematically explore their functional properties. This engineering approach offers a unique way to explore how cellular systems can balance (seemingly paradoxical) functional properties – e.g. specific computation, functional robustness, and adaptability – in order to learn about their evolutionary design, understand their role in development and disease, and guide the engineering of cells with sophisticated functions for practical application. On a translational level, we are applying our synthetic biology technologies to address unmet biomedical needs. This includes creating gene expression control schemes for next-generation gene and cell therapy, and new cell-based models and screening platforms for neurodegenerative disease. In parallel to our synthetic biology efforts, we invent high-throughput technologies / devices and use quantitative systems approaches to help us experimentally interrogate both short-term adaptation and long-term adaptive evolution in microbial systems.

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Construction of a Synthetic, Chromatin-Based Epigenetic System in Human Cells
Minhee Park, Nikit Patel, Albert J. Keung and Ahmad S. Khalil
in revision

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, in press

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*, Jayamani Anandhakumar, Kendra Valerius, David S. Gross, Ahmad S. Khalil and David Pincus
eLife, 7: e31668 (2018)

A Genetic Tool to Track Protein Aggregates and Control Prion Inheritance
Gregory A. Newby*, Szilvia Kiriakov*, Erinc Hallacli*, Can Kayatekin, Peter Tsvetkov, Christopher P. Mancuso, J. Maeve Bonner, William R. Hesse, Sohini Chakrabortee, Anita L. Manogaran, Susan W. Liebman, Susan Lindquist and Ahmad S. Khalil
Cell, 171: 966-979 (2017)

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