Brian Burke

Brian Burke received his Ph.D. from Imperial College of the University of London where he carried out investigations into the molecular structure of human erythrocyte spectrin. This was followed by postdoctoral work with Graham Warren at the EMBL in Heidelberg and with Larry Gerace at Johns Hopkins University in Baltimore, Maryland. During this period he developed a longstanding interest in the structure and function of the nuclear envelope.

After a period as staff scientist at the EMBL, Dr. Burke joined the faculty of Harvard Medical School in the Department of Cell Biology. He later served as Professor of Cell Biology and Anatomy at the University of Calgary and as the Haskell Hess Professor of Cell Biology at the University of Florida College of Medicine. Since August 2009, Dr. Burke has been a Principal Investigator at the IMB.

Dr. Burke’s 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.

 (Left) Overview of LINC complex organization. Inner nuclear membrane SUN domain proteins function as
tethers for outer nuclear membrane nesprins. Together these proteins represent links in a molecular chain
that connects nuclear components to the cytoskeleton.

(Right) Nesprin 4 (in green) is a new member of the nesprin family and has the capacity to bind kinesin,
a microtubule motor protein. Expression of nesprin 4 in HeLa cells is associated with the displacement
(indicated by the yellow arrow) of the centrosome (red) from its normal location adjacent to the nucleus.
DNA within nuclei is shown in blue.