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SUMMARY:Studying the invasive migration of Drosophila immune cells. - Prof
 essor Daria Siekhaus\, IST Austria (Institute of Science and Technology Au
 stria)
DTSTART:20140220T143000Z
DTEND:20140220T153000Z
UID:TALK49225@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:Both metastatic cancer cells and immune cells pursuing infecti
 ons must penetrate the adherens junctions present in the endothelial barri
 er of the blood vessel wall to reach tissues.  This transmigration require
 s the Rap1 GTPase to modulate Integrin affinity.  We have defined a step i
 n the developmental migration of Drosophila macrophages that we believe ca
 n serve as a model system to dissect the genetic pathways that control suc
 h transmigration.  Using live imaging and genetics\, we have discovered th
 at Drosophila melanogaster immune cells penetrate an epithelial\, DE-Cadhe
 rin-based tissue barrier during their embryonic developmental movements in
 to the tail.  A mutant in RhoL\, a GTPase homolog that is only expressed i
 n Drosophila macrophages at this stage\, specifically blocks this invasive
  step but not other aspects of guided migration.  The invasion defect in r
 hoL mutants can be rescued by lowering embryonic DE-Cadherin levels\, argu
 ing that RhoL is required to allow hemocytes to penetrate adherens junctio
 ns.  We also show that RhoL is localized to the cell surface and mediates 
 Integrin adhesion in hemocytes.  We observe that RhoL mutants fail to tran
 sport the Integrin activator Rap1 from a cytoplasmic concentration to the 
 leading edge during invasion. We have identified many mutants in genes exp
 ressed in hemocytes with defects in movement into the tail\, two of which 
 have been linked to metastasis in mice.  My lab is utilizing these mutants
  to try to shed new light on the process of invasive migration\, and will 
 try to translate these findings into vertebrate systems.  I will discuss o
 ur latest findings on a few of them.
LOCATION:Part II Room\, Department of Genetics
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