Analysis of protein/nucleic acid complexes by native ion mobility-mass spectrometry.

Many of the functions of nucleic acids (DNA, RNA) depend on their precise 3D structure, and how they interact with proteins. If we want to understand the molecular basis of diseases or infection, we have to understand those interactions during the cell cycle and protein synthesis. The proteins that interact with nucleic acids typically play important roles in the structure and activity of the genome. In this PhD project we will work on protein assemblies that interact with nucleic acids and are involved in DNA structural and spatial organization and gene regulation. This includes analysis of the structure and composition of key cellular complexes as well as their mode of operation, with the help of native Mass Spectrometry (MS) and Ion Mobility (IM). These methods allow us to get information about the mass, charge and also about the size and shape of the molecular complexes.We will work within several international collaborations (Oxford, Bristol) which focus on Structural Maintenance of Chromosomes (SMC) proteins and their associated binding partners, which organize DNA during the cell cycle. This project also includes the development of novel methods for native MS of proteins and protein/nucleic acid complexes, and the use of modeling approaches to interpret the data and propose global structures of the assemblies. In this way, we hope to link information on genome management on a molecular level with mechanisms of inheritance and physiological adaptation.

Keywords:PROTEIN COMPLEXES, MASS SPECTROMETRY, STRUCTURAL BIOLOGY, CHROMOSOMES