The central dogma of molecular biology postulates that genetic information flows linearly from DNA, the faithfully maintained blueprint of life, into RNA, the intermediate messenger, onto functional proteins, the machinery of our cells.
DNA, however, is much more than a simple linear code; it is packaged into a complex three-dimensional dynamic structure called chromatin in which DNA is wrapped around proteins known as histones. The compact nature of these structures restricts accessibility to genes. Indeed, 97 per cent of our DNA is packaged as heterochromatin – the dark matter of the genome and is thus inactive at any one time.
Not much is understood about heterochromatin, but its malfunction leads to cancer, developmental defects and susceptibility to infectious diseases.
Our lab seeks to understand the fundamental principles behind the formation, regulation and repair of heterochromatin. We hope to use these insights to discover new druggable targets.
Lab’s mission: Seeing small in a big way.
Lab’s vision: To directly visualise biological processes to enable their functional significance to be understood and, in turn, inform the rational design of new medicines for diseases.
Heterochromatin formation in a specific region of the genome leads to its inactivation. Such physical alteration of our DNA without changing the underlying genetic code is a complex process undertaken by large protein complexes. Our lab investigates how such large protein complexes perform this function.
Double-stranded DNA breaks in heterochromatin are repaired by a process of homologous recombination by exchange of genetic material between two sister chromatids. Our lab investigates how this process works in highly repetitive regions of heterochromatin without leading to fragile chromosomes.
Different human RNA viruses use different strategies to invade the host cells including interaction of viral surface proteins with membrane proteins of host cell membrane. Our lab investigates in atomic details how human RNA viruses interacts with attachment and co-receptors on host cells.
The Shakeel lab is a newly established multidisciplinary team that focuses around electron cryo-microscopy and is complemented by biochemical and biophysical techniques.
We collaborate with other laboratories in the Structural Biology and Epigenetics and Development divisions and WEHI. We are always interested to hear from enthusiastic candidates at all career stages.