Physics

 

Research Interests:

I aim to better understand the complex behavior of living systems through the use of reconstituted model systems. My current focus is the biopolymer actin, a key component of the cellular cytoskeleton, and the actin binding proteins (ABPs) that regulate actin’s mechanics and dynamics in vivo. By using reconstituted systems of actin and its binding partners, we can begin to dissect the role and mechanisms of each component.

Actin mechanics and stability
Basic calponin is a smooth muscle ABP believed to play a role in cytoskeletal stabilization. As a first step to understand how calponin functions mechanistically, I study the effects of calponin on the mechanics of single actin filaments. I also collaborate with the Weitz lab at Harvard University, using bulk rheology and microrheological techniques to characterize the mechanics of actin networks with and without calponin. Current results suggest that calponin increases the tensile strength of actin networks purely through direct mechanical interactions. The work also suggests a possible mechanism of calponin function, in which calponin increases the compliance of individual filaments, which leads to a delayed failure of the network.

Actin assembly and dynamics
In addition to actin mechanics, actin assembly and dynamics are also closely regulated and important parameters governing the overall cytoskeletal behavior. In collaboration with Dr. Chih-Lueh Albert Wang (http://www.bbri.org/index.php/our_scientists/articles/wang.html), I am studying the effects of H32K, a C-terminal fragment of the smooth muscle protein caldesmon, on actin structure and dynamics. We recently demonstrated that H32K prolongs a nascent state of polymerizing actin without altering the growth dynamics. This nascent state is hypothesized to alter the interactions of F-actin with other ABPs. One key ABP of interest is the protein complex Arp2/3, which nucleates and branches actin. Together with Dr. Wang and Eliza Morris of the Weitz lab at Harvard University (http://weitzlab.seas.harvard.edu/research/morris-eliza.html), I recently demonstrated that H32K-stabilized nascent actin filaments more readily bind Arp2/3 and form branched structures. My main techniques include total internal reflectance fluorescence microscopy (TIRFM), which is designed and built by myself and others in our lab, and confocal microscopy.

Intracellular mechanics
In collaboration with Ming Guo of the Weitz lab at Harvard University (http://weitzlab.seas.harvard.edu/research/guo-ming.html), I study the intracellular mechanics of whole cells using microrheological techniques. Optical tweezers designed and constructed by myself and others in our lab are used to manipulate injected beads in the cell interior to quantify the local mechanical environment in terms of the storage and loss moduli. Our recent work on A7 cells has elucidated how the cell, despite being a largely elastic material, can allow passive transport of objects much larger than the network mesh size.

Selected papers:

• 09/07/12 The conformational state of actin filaments regulates branching by actin-related protein 2/3 (Arp2/3) complex
• 01/20/12 Effects of Basic Calponin on the Flexural Mechanics and Stability of F-actin
• 05/25/11 Structural studies on maturing actin filaments
• 06/23/07 Domain Shapes, Coarsening, and Random Patterns in Ternary Membranes

Education:

B.S., Physics and Mathematics, University of Southern Denmark (Odense) 2005.
M.A., Physics, Boston University, 2009.

Honors/Awards:

- GRASP graduate research fellowship, Boston University, Boston, MA. 2011
- Travel grant, ESF/EMBO Symposium, Sant Fileu de Guixols, Spain. 2010
- 2nd place poster prize, New England Society of Microscopy meeting, Woods Hole, MA. 2010
- National Science Foundation GK-12 fellowship, Boston University, Boston, MA. 2008
- Boston University Physics Department teaching fellow of the year, Boston University, Boston, MA. 2008