|Class of 2002
Graduated in 2007
|Undergraduate Institution: Massachusetts Institute of Technology
Major: Biology and Physics double major
Origin: Boston, MA
|Lab: Jamie Cate
Location: Calvin Lab
Characterization of Ribosome Energetics under Macromolecular Crowding
The characteristics of biological macromolecules are often studied under in vitro conditions that attempt to emulate in vivo environments. The important in vivo effects of macromolecular crowding are, however, seldom addressed by biologists. Though crowding may not be important in understanding the basic properties of proteins or nucleic acid polymers, it can be crucial in modeling the behavior and interactions of such macromolecules inside the cell, where 20-30% of the total volume is occupied by macromolecules. Ribosome activity has, for example, typically been studied at concentrations of 1M, whereas its concentration in bacterium can exceed 50M. By decreasing the configurational entropy or the diffusion constant of various proteins, crowding can have productive and destructive consequences; crowding can promote the formation of multi-enzyme complexes, but it can also stimulate the formation of nonfunctional aggregates. As a molecular machine with many components, the ribosome must assemble and function in a highly coordinated fashion to achieve both speed and accuracy. The manner in which this happens in a crowded intracellular environment has yet to be elucidated. All steps in translation - initiation, elongation and termination - involve multiple components and interactions, and are thus likely affected by crowding.
Elucidation of ribosomal function under macromolecular crowding, in particular the characterization of the elongation cycle, will provide a more complete and accurate picture of ribosome behavior in vivo, which may ultimately lead to the development of new antibiotics targeting steps in translation. In addition, I believe that this work will lay the foundations for studying the biological effects of volume exclusion by developing techniques that hold promise for general application in elucidating the behavior of other molecular machines, such as DNA or RNA polymerases, under macromolecular crowding.
- Z. L. Liau and A. A. Liau, Appl. Phys. Lett. 78, 3726 (2001)