In eukaryotes, in order for DNA to fit inside the nucleus of a cell, it is wrapped around histone proteins and packaged into chromatin. The tightly packed structure of chromatin is inhibitory to gene expression as the transcriptional machinery is unable to access the template DNA. There are a number of mechanisms through which chromatin structure is reglated, including post-translational modification of regulatory proteins and DNA methylation. These processes and the subsequent chromatin remodelling are controlled by proteins with enzymatic activity that are able to add or remove protein and DNA modifications or harness the energy from ATP hydrolysis to remodel the structure of chromatin. A number of these regulatory enzymes have been shown to exist in large multi-subunit complexes. Within these complexes, the enzymatic activity of the regulatory protein is often controlled by the other subunits of the complex as many of these other subunits have been implicated in directing the complex to the site of action and are known to enhance the enzymatic activity within the complex.

We are working to understand the structure and function of one such complex: the nucleosome remodelling and deacetylase (NuRD) complex.

 The major focus of my work has been to obtain a low- to medium-resolution structure of this complex using negative stain electron microscopy with the hope that a deeper understanding of how the complex works will further our understanding of the mechanisms governing gene regulation in higher organisms.