The overall aim of the Genome Biology Program is to understand the connection between genomes and phenotypes and how this relationship is regulated in response to environmental and intrinsic signals crucial for cell or organismic survival and homeostasis. Understanding this connection will uncover the aetiology of many diseases that involve individual genome differences and genome instability, which will have a direct impact on the new field of genomic medicine.
Using integrative genomic, genetic and biochemical approaches, our specific aims are:
- Deciphering the complex nature of the information encoded by genomes and how this genomic information differs from one individual to the next. It is becoming clear that in addition to the simple genetic encoding of proteins, the genome contains much more genetic information than first realised. Developing new bioinformatic methods and by employing a comparative evolutionary approach, we are identifying new functions for genomic sequences and uncovering novel DNA sequences that vary between individuals.
- How the expression of genomic information is both regulated and integrated to create complex networks needed to direct biological processes including development and disease. We are investigating how the flow of information from the genome is regulated by its organisation into the epigenome. In particular, we are integrating the role of the epigenome with key signalling and transcription molecules and elucidating the regulatory architecture of gene expression. The development of new statistical models and approaches for genome-wide analyses are critical to achieving this aim.
- Most genomic regions can be actively transcribed leading to a myriad of distinct RNA molecules, some coding for proteins but most are likely to have diverse regulatory functions. We are decoding the principles of this RNA-level regulation, with an emphasis on the dynamic and highly combinatorial interactions of RNA with proteins to form functional ribonucleoprotein particles. Proteomic and transcriptomic measurements and their computational analysis are key to these activities.
- How genomes are structurally organised to establish functional domains that are stably maintained across generations especially during stem cell and germ cell differentiation. We are interested in the structure of chromosomes, and how chromosomes segregate properly during mitosis and meiosis. We are also focusing on the evolution and function of DNA tandem repeats in the human genome including the mechanisms that keep retrotransposons silent.