People

Dr. Timothy Gardner received his B.S. in Mechanical Engineering from Princeton University in 1995 and his Ph.D. in Biomedical Engineering from Boston University in 2000. In the spring of 2000, he co-founded Cellicon Biotechnologies, a company developing improved antibiotics through the mapping and control of cellular gene circuitry. In September of 2003, he was appointed to Assistant Professor of Biomedical Engineering at Boston University. Dr. Gardner also currently serves on the Board of Directors of Cellicon.

Research Interests

• Genetic network inference, analysis and control via scalable methods.
• Optimization of microbial metabolic networks for bioremediation and energy production.
• Analysis and control of bacterial stress response to overcome antibiotic tolerance.
• Inference of drug mechanism of action.

Current Research

Microbial organisms are something of a double-edged sword for humankind. They can cause debilitating or fatal infections; but they are also the source of many therapeutic drugs, may be used to detoxify polluted environmental areas, and may even offer solutions to the world's expanding demand for energy. To identify novel treatments that overcome bacterial resistance, and to unlock the full catalytic potential of microbes for bioremediation and energy production, a clearer understanding is needed of the complex systems of genes, proteins and metabolites underlying cell function. We are currently focused on developing computational and experimental tools for mapping and modeling system-wide properties of gene regulatory networks in microbes. To this end, we have recently developed a network inference method (Network Identification by multiple Regression-the NIR method) and successfully applied it in E. coli.

We are now working to improve such network inference methods for greater precision and extend them for application to a broader set of biological systems and conditions. Current projects include:

• Development of more versatile experimental perturbation tools;
• Capture of nonlinearities important to sporulation, development, viral infection;
• Integration of protein data, metabolic data and prior information;
• Large-scale inference of networks relevant to bioremediation and antibiotic tolerance.

Selected Recent Publications

Faith JJ, Hayete B, Thaden JT, Mogno I, Wierzbowski J, Cottarel G, Kasif S, Collins JJ, Gardner TS "Large-scale Mapping and Validation of Escherichia coli Transcriptional Regulation from a Compendium of Expression Profiles" PLoS Biology : (2007)

di Bernardo D, Thompson MJ, Gardner TS, Chobot SE, Eastwood EL, Wojtovich AP, Elliot SJ, Schaus SE, Collins JJ "Chemogenomic Profiling on a Genome-Wide Scale Using Reverse-Engineered Gene Networks" Nature Biotechnology 23: 377-383 (2005)

Kobayashi H, Kaern M, Araki M, Chung K, Gardner TS, Cantor CR, Collins JJ "Programmable Cells: Interfacing Engineered and Natural Gene Networks" Proceedings of the National Academy of Sciences USA 101: 8414-8419 (2004) abstract

Gardner TS, di Bernardo D, Lorenz D, Collins JJ "Inferring genetic networks and identifying compound mode of action via expression profiling" Science 301: 102-105 (2003)

TS Gardner "Genetic Applets: biological integrated circuits for cellular control" IEEE International Solid-State Circuits Conference: Digest of Technical Papers 44: 112-113 (2001)

Gardner T.S., Cantor C.R., Collins J.J. "Construction of a genetic toggle switch in Escherichia coli" Nature 403(6767): 339-42 (2000)