Posttranslational modification of HMGN1 in DNA packaging

Just as a library contains a vast amount of information in many books and documents, each of our cells contains all the genetic information needed for the features and functions of that cell. In a library, an organized system of shelves, cabinets and catalogues helps us to find the information we want at a particular time. In cells, special proteins help to pack and unpack DNA so that the genetic information can be expressed at the correct time and place. If we modify the design and arrangement of the shelves in a library, this can change how easily we can access information contained in the books. Similarly, the proteins that package DNA are modified at various times and cellular conditions to regulate access to genetic information. In this project, we aim to understand how modifications to one of these proteins - called HMGN1 - affects how DNA is packaged. To do this, we will use the tools of protein chemistry to make differently modified versions of HMGN1 so that we can study how each modification or combination of modifications affects DNA packaging. We will use structural biology techniques to study how the modifications change the three-dimensional shape and movement of HMGN1 and how it interacts with other proteins. This project uniquely combines protein chemistry and structural biology techniques, allowing us to make specifically modified proteins, and to study their structural and functional effects. The outcomes of this work include new methods for making and studying modified proteins and a better understanding of how access to genetic information is regulated in healthy and diseased cells.