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SUMMARY:Signalling Networks in Cell Proliferation and Fate Control - Profe
 ssor Sibylle Mittnacht\, UCL Cancer Institute
DTSTART:20121106T120000Z
DTEND:20121106T130000Z
UID:TALK35876@talks.cam.ac.uk
CONTACT:Dr Ireena Dutta
DESCRIPTION:Control of cell division is a prerequisite for the precise for
 mation of organs and body organization during embryonic development as wel
 l as tissue renewal and tissue maintenance thereafter. A defect in this co
 ntrol is elementary to the development of cancer and found in cancer cells
  of all cancer types. Because of such defects cancer cells enter division 
 independent of external control and remain proliferation active under cond
 itions where normal cells are unable\, or cease\, to divide. Loss of divis
 ion control is critically important for the ability of cancers to expand a
 t their primary site as well as for the ability of cancer metastasis to es
 tablish following spreading of individual cancer cells to remote tissues. 
 We are trying to understand the molecular machinery required for cells to 
 enter the cell division cycle and the mechanisms that leads cells to cease
  division activity transiently and terminally. The decision whether to ent
 er cell division arises in the GAP1 (G1) phase of the cell cycle and norma
 lly required stimuli from the external environment.\nKey components contro
 lling exit from G1 and onset of S phase are the cyclin D-dependent kinases
  CDK4 and CDK6\, and the cyclin E-associated kinase CDK2\, which phosphory
 late and through this inactivate the retinoblastoma tumour suppressor prot
 ein (RB1). Genetic alterations that weaken or disable G1 checkpoint contro
 l are extremely frequent in cancers and presumed to promote cancer develop
 ment by permitting unlicensed proliferation. Conversely\, G1 checkpoint ac
 tivation ensues in response to stress\, including genotoxic insult and in 
 such contexts is thought to provide resistance to therapy- and cancer inhe
 rent adversities.\nAlthough the key components of G1 checkpoint execution 
 are recognised our understanding how G1 inherent signalling and stresses o
 perate to modulate checkpoint function is far from complete. We developed 
 a high throughput assay format allowing quantification of the phosphorylat
 ed\, inactive form of RB1 in fixed cells seeded in a 96 well format. This 
 assay in combination with targeted knockdown using siRNA libraries is iden
 tifying known and unexpected signalling required for checkpoint modulation
  in the different contexts. Results from these screens and their implicati
 ons will be discussed. \n\n
LOCATION:Sackler Lecture Theatre (Level 7)\, Cambridge Institute for Medic
 al Research
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