This application outlines a collaborative research plan to be carried out by the Principal Investigator (Williamson) with Dr. Alexey Karnaukhov at the Institute of Cell Biophysics in Pushchino, Russia. The parent grant is GM-53757, """"""""Assembly of the SOSribosomal subunit"""""""". The overall goal of the parent grant is to study the mechanism of assembly of the SOS ribosome, which is composed of a large 16S ribosomal RNA, and 20 small proteins. The SOS subunit can be reconstituted in vitro, and one of the major goals of the parent grant is to study the kinetics of the process. An isotope pulse chase assay has been developed that allows monitoring of binding rate of all 20 proteins simultaneously. The kinetics are extremely complex, and both parallel and sequential binding is observed. There are many intermediates formed, and the kinetics are extremely complex. The goal of the FIRCA application is to collaborate with Dr. Karnaukhov, who is an expert at the analysis of nonlinear dynamic data. He has developed new analytical approaches that can be directly applied to the problem of ribosome assembly. We have already initiated a collaboration to develop new tools for the analysis of complex kinetic data based on this common interest. This application seeks to support this interesting and important work. The proposed work is specifically significant for the ribosome assembly problem, and is more generally significant because the tools we develop will have broad applicability in understanding complex reaction dynamics in chemistry, biochemistry, and cell metabolism. The research will be done primarily in Russia at the Russian Academy of Sciences, in collaboration with Dr. James R. Williamson as an extension of NIH grant* R01 GM053757.
| Karnaukhov, Alexey V; Karnaukhova, Elena V; Williamson, James R (2007) Numerical Matrices Method for nonlinear system identification and description of dynamics of biochemical reaction networks. Biophys J 92:3459-73 |
