A lot of interesting biology inside the cell emerges from the dynamics of large molecular complexes. The length scales involved are on the order of tens of nms, and are typically difficult to probe because of fundamental limits in optical microscopy. We are interested in developing new fluorescence spectroscopy techniques which can measure organization at these length scales.  Our favorite tool is Single Molecule Tracking Microscopy, where we use feedback techniques to observe individual molecules diffusing in solution for long periods of time, and glean information about their conformation.

Single Molecule Tracking Microscopy

The project is at the crossroad between optics, control theory, signal processing and biology. The signals we obtain with single molecule tracking are stochastic at several levels (random motion of the molecule, random molecular dynamics, and stochastic fluorescence). Encoding the information in these signals (by clever optical design and feedback) and decoding it in an optimal way is one key aspect of this research.

We work in collaboration with several Biochemistry labs to tackle important questions in cellular and molecular biology. We are particularly interested in understanding how the genome is spatially organized inside the nucleus of eukaryotic cells. Using reconstituted systems, we aim to tease apart the biophysical and biochemical mechanisms of chromatin folding and their implications on genetic regulation (Straight Lab). We are also interested in RNA folding principles and are developing new FRET assays to measure fast dynamics of RNA molecules (Herschlag Lab). In addition, we study the biophysics of membrane trafficking in human cells, in particular the processes by which tethering proteins capture vesicles and facilitate membrane fusion (Pfeffer Lab).

A view of the single molecule tracking microscope

.. and some of the feedback electronics