Gene regulation and morphogenesis

1. Non-canonical DNA methylation as a regulator of embryonic genome function

We have recently described embryonic reprogramming of non-canonical DNA methylation (mCH, where H = C, T, A) within mosaic satellite repeats (MOSAT mCH), coincident with zygotic genome activation (Ross et al, 2020; Nuc Acids Res). Our CRISPR/Cas9 functional analyses in zebrafish larvae have unravelled Dnmt3ba as the primary MOSAT mCH methyltransferase enzyme. By using CRISPR/Cas9 and Cas13d genome editing technology in zebrafish, we are functionally interrogating the contribution of mCH and Dnmt3ba to embryogenesis, to better understand the developmental requirements for proper mCH patterning.
 

2. The rogue germline: epigenetic regulation of cancer testis antigens in embryonic development and cancer

A surprisingly small number of genes becomes silenced by promoter DNA hypermethyation during vertebrate embryogenesis. In many cases, these genes are essential regulators of germline development that are frequently found altered in multiple adult cancers. Through a combination of biochemical and zebrafish transgenesis approaches we are trying to understand the mechanisms of this targeting specificity as well as the roles of these genes in embryonic development cancer formation in vivo.
 

3. Bluebottle blues: System level characterisation of the siphonophore, Indo-Pacific man o' war (bluebottle)

The overarching objective of this project is to utilise system level approaches and functional analysis to establish foundation knowledge of the Indo-Pacific man o' war (bluebottle), a marine animal that is infamous for their painful sting. Bluebottles are not jellyfish, yet are siphonophores, a remarkable group of animals that are made up of colonies of highly modified individuals (zooids). This makes them an exciting species to study at the genome, epigenome and proteome levels to further our understanding of animal multicellularity and toxins.