When Watson and Crick revealed the DNA “double helix” (CCB Logo) as the structure that transmits our genetic inheritance, it inspired scientists to study DNA as the basis for understanding how molecules lead to biology and life.

Ironically, however, obtaining the ultimate picture of DNA through determining the human genome sequence has caused our perspective to change. The vastness of our DNA and the inherent challenges for the cell in managing it has been highlighted. The 3 billion chemical basepairs held in each human cell represent about the same number of letters as contained in all the books in a typical city library. Yet the simple sequence of the double helix alone does not provide enough blueprint to determine what occurs in the cell.

An important additional component of genetics is the packaging that envelops DNA which plays a crucial role in encoding and enabling life. The packaging is called chromatin: the material that makes up chromosomes into which our genome is divided. The study of chromatin and chromosomes is the foundation of our research in the Centre for Chromosome Biology.

Chromosomes were first observed within the human cell nucleus in the mid-1800s and were recognised as the carriers of genetic information by the 1900s. The place of DNA as their basis was confirmed by the middle of the twentieth century. The subsequent focus on DNA as the genetic material led to the view that chromosomes were just a convenient packaging for DNA. The importance of the order and regulation that packaging provides (dividing libraries into books with chapters and paragraphs) was overlooked.

Such ordering allows our cells to reliably find, maintain, distribute and copy every ‘page’ of protein information within its DNA library which is crucial to enable life. Similar to library organisation, the chromosome has a hierarchical order from the familiar X shape down through many smaller levels (see diagram above) to a cotton-reel like molecular packaging on protein spindles which is the building blocks of chromatin (equivalent to the page of a book).

Our work in the Centre for Chromosome Biology revolves around understanding the makeup of chromatin and the processes which act on it to facilitate all the processes needed to sustain life. We are interested in how DNA has evolved through mutations (Gahan Group) and how mutations can go awry (Lahue Group). We try to further our understanding on how DNA is packaged into nucleosomes (Flaus Group) with modifiable histones (Rea Group) that make up the chromatin which must be replicated (Santocanale Group, Nasheuer Group), segregated at centromeres (Dunleavy Group, Sullivan Group) and separated by centrosomes (Morrison Group) into daughter cells that divide in cytokinesis (Luessing Group).

The main function of chromatin is to produce proteins using ribosome machines assembled at nucleoli (McStay Group). What proteins a cell can or cannot produce is controlled by areas of opened or closed chromatin and is specialised to different cell types (Frank Group). Examples of this are insulin produced in the pancreas, keratin in our hair, and melanin in our skin. Melanin protects the chromatin in our skin cells from double strand breaks (Lowndes Group) caused by UV radiation. While our cells are equipped with a DNA damage response (Carty Group), it can make mistakes just like any of these other processes, and lead to diseases like cancer. As such, our research can have important impacts on health and medicine in addition to enlightening our fundamental understanding of chromosome biology.