The chromatin landscape of a cell is subject to various “epigenetic” modifications that direct gene expression, allowing different cell-types to emerge from the same genetic information. Crucially, this epigenetic information must be inherited through cell division to allow specific cell lineages to propagate, modified to promote cellular differentiation, and protected from unscheduled changes that lead to complex diseases like cancer. Histone proteins wrap DNA to form nucleosomes, the basic repeating subunit of chromatin, and the post-translational modification of histones and their location in the genome is an important source of epigenetic information. During DNA replication this information is inherited through the recycling of old histones and complemented by the supply and deposition of new histones to restore nucleosome density. This creates a vast demand for the delivery of newly synthesised histone proteins for DNA replication-coupled chromatin assembly. Meanwhile, the delivery of newly synthesised histones to chromatin is streamlined by dedicated histone chaperone proteins. Defective histone supply undermines genome integrity, cell identity and promotes alternative lengthening of telomeres – traits of neoplastic transformation/cancer initiation. Thus it is imperative for cellular health to have well-tuned and well-functioning histone supply chains that ultimately support the structural and epigenetic integrity of chromatin.
Through my research I have applied structural biology, in vitro assays and mechanistic cell biology to study how soluble histones are supplied to chromatin for de novo nucleosome assembly. My work has led to the realisation that histone chaperones cooperate by forming histone co-chaperone complexes whereby two or more histone chaperones are brought together in a histone-dependent manner due to compatibilities of their histone binding surfaces. These histone co-chaperone complexes form nodes within a network-like structure as each histone chaperone can form several discrete histone co-chaperone complexes. We have characterised new connections to cellular protein folding machinery, gene silencing pathways and several other processes by studying the organisation of the histone chaperone network.
In my lab we are studying how various other cellular processes integrate with the histone chaperone network. We are especially interested to study how these processes go wrong in cancer with the aim of translating our textbook discoveries into future therapeutics. I have a broad scientific background, an undergraduate in chemistry, PhD in structural biology and postdoc in mechanistic cell biology and proteomics. My lab draws on these influences by promoting the pursuit of projects from a multidisciplinary scientific perspective and recognises the many strengths that diversity adds to our team, workplace and society.