The human cell nucleus is a highly organised biological structure. The genome is packaged within the nucleus in such a way as to facilitate many essential processes, including gene transcription, replication and repair of the genome.
The nucleus is highly compartmentalised, containing numerous nuclear bodies with distinct functions. Determining how the genome is organised and how nuclear bodies are formed is a major goal of modern biology.
The nucleolus, the site of ribosome biogenesis, is the most prominent nuclear body in all eukaryotic cells. Nucleoli form around arrays of ribosomal genes termed nucleolar organizer regions (NORs).
In humans, NORs are located in uncharted regions of the human genome, the short arms of the acrocentric chromosomes.
Our aims are to elucidate the chromosomal context of NORs and determine how their structure facilitates nucleolar formation.
We employ chromosome engineering, genomics and cell biology to address these questions. This work has additional significance as control of ribosome biogenesis is intimately connected to cellular growth and proliferation and is disregulated in many human diseases including cancer.