Cooperativity in Nucleic-Acid Protein Interactions

Ohio State University, The, Columbus OH

Investigators

Abstract

NON-TECHNICAL SUMMARY Any life form has to react to changes in its environment. In order to do so, it has to be able to process information. Information processing within individual cells boils down to interactions between different biomolecules that can come together in a multitude of different combinations. In order to process information, these interactions have to be cooperative, i.e., the interactions between one set of molecules have to depend on the presence or absence of other molecules. The PI's group will develop theoretical methods to model such cooperativity that will provide a better fundamental understanding of biological information processing and possibly the ability to engineer future biological information processing circuits. The research will be focused on two of the most important types of biomolecules, nucleic acids and proteins, and will have two different components. The first component will address the question of how natural structural properties of nucleic acids can generate cooperativity and how this new mechanism is used by living organisms. The second component will be of a more technological nature and will aim at improving the utilization of protein nucleic acid interactions to measure DNA methylation, a feature of cells that is known to be affected in many diseases. This project will contribute to the training of a new generation of researchers equipped with mathematical and biological skills that are important for the future progress in the life sciences. This will be achieved through students' education in Biophysics Graduate Program and participation in Biophysics Seminar series at the Ohio State University. TECHNICAL SUMMARY This project will develop quantitative models to describe cooperativity in interactions between proteins and nucleic acids. Such interactions are at the foundation of biological information processing as well as of biotechnological applications. Accurate theoretical models make interpretation of today's quantitative experiments possible and allow a fundamental understanding of biological mechanisms and extraction of "hidden" parameters from measurements. Within this context, the project consists of two parts. The first part will address effect of RNA secondary structure on cooperativity of proteins binding and elucidate mechanism of how natural messenger RNAs implements logic operations among different protein "inputs" in post-transcriptional regulation. The second part consists of the development of a detailed model of the interactions between several MBD2 methyl-binding domains and (methylated) DNA molecules. These MBD2 domains are used in experiments for determining DNA methylation status in a genome-wide manner and it is anticipated that the model to be developed will improve accuracy of these DNA methylation measurements. Such genome-wide measurements of DNA methylation are of interest since DNA methylation is known to be affected in many diseases.