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DTSTAMP:20260916T192557Z
LAST-MODIFIED:20150330T142756Z
DTSTART:20150401T200000Z
DTEND:20150401T210000Z
UID:event1437@bu.edu
URL:http://physics.bu.edu/internal/events/show/1437
SUMMARY:Controlling allosteric networks in proteins
DESCRIPTION:Featuring Nikolay V. Dokholyan\, University of North Carolina\n
	Hosted by: H. Eugene Stanley\n\nPart of the Biophysics/Condensed Matter Sem
	inar Series.\n\nABSTRACT:\n\nFor many cellular behaviors\, it is essential 
	that signaling is precisely\ncoordinated in space and time. Such spatiotemp
	oral dynamics can only be\nfully understood using tools that examine and ma
	nipulate protein\nbehavior in intact living cells. While it is very valuabl
	e to visualize\nsignaling dynamics\, testing hypotheses about spatio-tempor
	al regulation\nrequires that we actually control such activity by manipulat
	ing protein\nactivity at precise times during live cell behavior. We develo
	ped an\napproach in which insertion of a ligand-controlled engineered domai
	n\n(uniRapR) into the loops that are allosterically coupled to active\nsite
	s. Such a domain renders kinases catalytically inactive; addition of\na sma
	ll molecule rapamycin rescues the catalytic activity by binding to\nuniRapR
	 domain. We validated our tool by building switchable Src-family\nkinases i
	n single cells and zebrafish. Activation of Src kinase leads to\nrapid indu
	ction of protrusion with polarized spreading in mamalian\ncells\, and morph
	ological changes with loss of cell–cell contacts in the\nepidermal tissue
	 of zebrafish. Currently\, we are extending this approach\nby controlling o
	ther protein families including guanine nucleotide\nexchange factors (GEFs)
	. These switchable GEFs will allow us to\ninvestigate GEF-GTPase circuit dy
	namics in migrating cells.
LOCATION:SCI 328\, 590 Commonwealth Avenue\, 02215
STATUS:CONFIRMED
CLASS:PUBLIC
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