Our lab uses a set of interdisciplinary approaches to examine molecular events in cells and piece them together, using computational models, into quantitative models of cellular behavior.  We use a range of biochemical, microscopy and spectroscopy-based techniques to investigate protein function through complex formation, dynamics and localization in living cells.  These data are then put together into kinetic computational models that attempt to approximate specific cellular functions and used to predict novel behaviors in silico.

Specifically, the lab utilizes engineered mammalian cell lines and those derived from transgenic mice to provide unique intracellular contexts to probe protein function.  Much of the information for protein function is derived from live cell measurements, either through simple widefield fluorescence microscopy or fluorescence correlation and lifetime techniques that yield quantitative interaction data.

We are currently focusing on three major cell biology areas in which to apply our interdisciplinary approach:  (1) the mitotic checkpoint – a biochemical and biophysical signaling network that prevents untimely chromosome segregation, (2) intraflagellar transport – a cellular network that builds and maintains tubulin-based structures such as cilia and flagella and (3) synthetic genetic networks – engineered genetic circuits that allow us to probe fundamental molecular mechanisms in transcription and translation.

Selected References

Shah J. V., Botvinick E., Bonday Z. B., Furnari F., Berns M. W., Cleveland D. W. 2004. Dynamics of centromere and kinetochore proteins: implications for checkpoint activation and silencing.  Current Biology. 14:942-952.

Botnivick E. L., Venugopalan V., Shah J. V., Liaw L. L., Berns M. W. 2004. Controlled Ablation of Microtubules using a Picosecond Laser. Biophysical Journal. in press.

Wang Z., Shah J. V., Chen Z., Sun C.-H., Berns M. W. 2004. Fluorescence correlation spectroscopy investigation of a GFP mutant-enhanced cyan fluorescent protein and its tubulin fusion in living cells with two-photon excitation. Journal of Biomedical Optics. 9(2):395-403.

Shah, J. V. And Cleveland D. W. 2002. Slow axonal transport: fast motors in the slow lane. Current Opinion in Cell Biology. 14:58-62.

Shah J. V. and Cleveland D. W. 2000. Waiting for anaphase: Mad2 and the spindle assembly checkpoint, Cell 103: 997-1000.