Our research will explore the physical properties of biological systems with optical microscopy techniques. We will be particularly interested in probing dynamical processes in living cells, and comparing these dynamics with those observed in vitro to understand the impact of the cellular environment. To accomplish this, we will use and develop live cell microscopies that are sensitive to molecular interactions and can follow dynamics over timescales of nanoseconds to hours. These methods will disturb the normal cellular processes very little, to give us an accurate view of living cells.

One particular area of interest is the movement and interactions of regulatory proteins in cell nuclei. For example, transcription factors that have been activated by environmental or cellular signals must be able to bind a specific DNA sequence that comprises only a miniscule fraction of the total DNA content. Similarly, DNA repair proteins must be able to efficiently detect sites of abnormal DNA structures. Our group will be interested in experimentally addressing the question of how proteins in the nucleus find their target binding sequence. We will employ a variety of techniques, including widefield, confocal and multiphoton imaging, fluorescence resonant energy transfer (FRET) and fluorescence correlation spectroscopy (FCS).

Our group will also develop novel microscopic techniques to improve biological imaging and enable us to extract more meaningful information about molecular interactions and dynamics in cells. In one area, we will use ultrafast laser pulses to record optically sectioned phase contrast images and measure orientation-dependent dynamics of molecules in distinct microscopic environments. We will also explore the spectroscopy of common biological fluorophores to learn how to reduce photobleaching and photodamage, particularly in multiphoton microscopy.