Philippe Cluzel, PhD
Department of Molecular and Cellular Biology, Faculty of Arts and SciencesCenter for Systems Biology
Gordon McKay Professor of Applied Physics, School of Engineering and Applied Sciences
Real-time analysis of signal transduction and genetic networks at the single cell level
Investigating genome-wide transcriptional dynamics, and studying multi-drug resistance in bacteria.
Dr. Cluzel’s research on multi-drug resistance has great implications for developing the next generation of antibiotics to treat drug-resistant bacteria. In studying multiple antibiotic resistance and the dynamics of the mar operon, Dr. Cluzel can determine whether epigenetic changes affecting the function of the mar operon are passed between generations. In addition, Dr. Cluzel is an expert in various techniques facilitating genomics research on a single-cell level.
Current Research Interests
Dr. Cluzel’s work is developing and applying tools for single-cell genomics research. The lab is pursuing a number of different topics, including genome-wide transcriptional dynamics in single cells, multi-drug resistance in bacteria, the effects of synonymous codons on gene expression, network topology and adaptability, and fluctuation-response in living cells.
To study genome-wide transcriptional dynamics, the lab is constructing a chip that will allow the study of thousands of colonies of cells for long periods of time. The lab has developed three techniques to aid this construction: growing bacteria in linear micro-colonies, microfluidics devices that allow micro-colony study under thermally and nutritionally controlled environments, and a widefield FCS instrument to monitor gene expression in multiple colonies. Specific projects in this area include the study of inheritance of epigenetic traits, the temporal dynamics of flagellar promoters, and memory in the carbon uptake system.
One main area of research in the Cluzel lab is multi-drug resistance in E. coli through activity of the mar operon. To date, the genetic and epigenetic characteristics of mar have been studied only at the population level, where differences between individual cells can be obscured. Techniques developed in the Cluzel lab allow study of mar on a single cell level, and have so far shown that mar activity levels can be inherited for multiple generations. The lab is also studying drug resistance in S. aureus (MRSA).
Other projects in the lab include studying the role of synonymous codons during cellular stress, for example, nutrient limitation in E. coli. The goal is to understand a dynamic aspect of the genetic code that is dependent on cellular environment; this research will lead to better heterologous protein expression in E. coli.
Tools and Assays
- Cell culture in linear micro-colonies
- Widefield FCS
Dr. Cluzel’s lab combines expertise in both biology and physics, using techniques such as statistical physics, computational biology, lasers, time-resolved fluorescence, video microscopy, protein-engineering, signal transduction, gene expression, and microbiology. The lab also has experience with growing bacteria in linear micro-colonies, and has designed a microfluidic assembly that allows thermal and nutritional control in the environment of these colonies, and maintenance of a constant colony size.