Engineering New Molecules
for Programming Complex Cellular Systems
Prof. Christina Smolke
California
Institute of Technology
Abstract:
Information flow through
cellular networks is responsible for regulating cellular function at both the
single cell and multi-cellular systems levels. One of the key limitations to
understanding dynamic fluctuations in intracellular biomolecule concentrations
is the lack of enabling technologies that allow for user-specified probing and
programming of these cellular events. I will discuss our work in developing the
molecular design and cellular engineering strategies for the construction of
tailor-made sensor platforms that can temporally and spatially monitor and
regulate information flow through diverse cellular networks. The construction
of sensor platforms based on allosteric regulation of non-coding RNA (ncRNA)
activity will be presented, where molecular recognition of a ligand-binding
event is coupled to a conformational change in the RNA molecule. This regulated
conformational change may be linked to an appropriate readout signal by
controlling a diverse set of ncRNA gene regulatory activities. Our research has
demonstrated the modularity, design predictability, and specificity inherent in
these molecules for cellular control. In addition, the flexibility of these
sensor platforms enables these molecules to be incorporated into larger
circuits based on molecular computation strategies to construct sensor sets
that will perform higher-level signal processing toward complex systems
analysis and cellular programming strategies. In particular, the application of
these molecular sensors to the following downstream research areas will be
discussed: metabolic engineering of microbial alkaloid synthesis and
'intelligent' therapeutic strategies.
Speaker Bio:
Christina D. Smolke is an
Assistant Professor in the Division of Chemistry and Chemical Engineering at
the California Institute of Technology. She graduated from the University of
Southern California with a B.S. degree in chemical engineering with a minor in
biology in 1997. As a National Science Foundation fellow, she attended the
University of California at Berkeley and earned her Ph.D. in 2001 in chemical
engineering under Professor Jay D. Keasling. There she worked on the design of
RNA control elements for regulating metabolic pathway flux in bacteria. Before
starting her position at Caltech, Christina served as a National Institutes of
Health postdoctoral fellow in cell biology at UC Berkeley. Under the guidance
of Professor Karsten Weis, she examined the role of nuclear export in the
nonsense-mediated decay pathway and the coupling between various RNA processing
pathways in eukaryotic cells. She began her current position at Caltech in the
beginning of 2004. Her laboratory is developing novel design platforms for
nucleic acid molecules and examining the application of these engineered
molecules in diverse areas such as programmed cellular behavior, 'intelligent'
therapeutics, and nanosensor devices. This research is rapidly advancing
current capabilities of assessing and programming cellular state. The
significant impact and innovative advancements of the technologies developed in
her laboratory have already gained recognition including the receipt of a
Beckman Young Investigator Award and a Technology Review's Top 100 Young
Innovators in the World under 35. In addition, she is the inventor on a number
of patents on technologies developed in her laboratory at Caltech. Christina
serves on the scientific advisory board of Codon Devices, a company working to
pioneer the emerging area of synthetic biology. She is a member of Caltech's
Center for Biological Circuit Design and Kavli Nanoscience Institute, the
American Institute of Chemical Engineers, the American Chemical Society, the
RNA Society, and the Institute of Biological Engineers.