Nuclear Dynamics & Architecture

Brian Burke and group members transferred to the Skin Research Institute of Singapore on the 1st April 2020.

Our research focus now concerns the mechanisms by which defects in genes encoding nuclear envelope proteins, including human A-type lamins, give rise to a variety of human diseases. These include forms of muscular dystrophy, lipodystrophy and Hutchinson-Gilford progeria, a premature aging syndrome. This work has led to discoveries that reveal how nuclear structures may be integrated with cytoplasmic components and have defined the functions of new families of nuclear membrane proteins, including SUN domain proteins of the inner nuclear membrane and nesprin proteins of the outer nuclear membrane.

Together, SUN proteins and nesprins represent pairs of links in molecular chains that span the nuclear envelope and which mechanically couple nuclear structures with the cytoskleton. These SUN-nesprin pairs, which we have termed LINC complexes (for LInkers of the Nucleoskeleton and Cytoskeleton) play a crucial role in nuclear positioning and migration in a wide variety of cell types. In addition, they may provide a new mode of communication between the cytoplasm and nucleus and could potentially mediate aspects of mechanotransduction.

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Both Sun1 and Sun2, the predominant SUN domain proteins of mammalian somatic cells, are localized to the nuclear periphery. DNA within the nucleus is shown in blue

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(Left) LINC complex components (red), including a new nesprin-like protein, are associated with telomeres in primary spermatocytes that are undergoing meiosis. DNA is revealed with a blue fluorescent dye while synaptonemal complexes, the structures that link homologous chromosome pairs, are shown in green. (Right) Aligned stack nuclei.