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SUMMARY:Three proteins walk into a &quot\;var&quot\;… - Dr Jessica Bryan
 t (Institut Pasteur\, Paris) 
DTSTART:20230517T150000Z
DTEND:20230517T160000Z
UID:TALK182798@talks.cam.ac.uk
CONTACT:Anna Protasio
DESCRIPTION:Antigenic variation is used by the most virulent malaria paras
 ite\, Plasmodium falciparum\, to evade the human immune system. The most i
 mportant variant surface antigen is encoded by a family of ~60 var genes t
 hat are expressed in a mutually exclusive fashion to ensure a sustained in
 fection. In this epigenetically-regulated process\, all var genes are comp
 acted into silent chromatin clusters at the nuclear periphery. Singular va
 r gene activation is concomitant with chromatin decompaction and separatio
 n into an ‘activation center’. While the basic epigenetic signatures o
 f silent versus active var genes are known\, much remains to be discovered
  about how they are regulated and organized within the nucleus. To identif
 y new proteins involved in this process\, we recently purified the var gen
 e promoter using immunoprecipitation with an enzymatically inactive Cas9 c
 oupled with mass spectrometry. We identified a protein complex including a
 n ApiAP2 transcription factor\, a putative microorchidia family protein (M
 ORC)\, and acetyl CoA synthetase (ACAS). Chromatin immunoprecipitation and
  sequencing confirmed that these proteins bind together and\, more specifi
 cally\, at the promoters of var genes found in subtelomeric regions. Induc
 ible knockdown followed by differential expression analysis showed that th
 e members of this complex are involved in controlling mutually exclusive e
 xpression of the var gene family. Ongoing work seeks to understand the rol
 e of these proteins in var gene regulation and organization and investigat
 es a potential link to parasite metabolism.\n\nThis is a hybrid talk. "Zoo
 m link":https://zoom.us/j/99521226700?pwd=OVJoRWQ1MWFCeTBrT0tDTVhRODFJdz09
LOCATION:Seminar Room\, Tennis Court Road\, Dept of Pathology.
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