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SUMMARY:Genome-wide functional profiling and its application to decoding m
 itotic regulation in trypanosomes - Dr Bill Wickstead (University on Notti
 ngham) 
DTSTART:20230426T150000Z
DTEND:20230426T160000Z
UID:TALK182792@talks.cam.ac.uk
CONTACT:Anna Protasio
DESCRIPTION:The mitotic machinery of protozoan parasites is often quite di
 stinct from host. That of trypanosomes is particularly divergent\, with mo
 st components showing no detectable similarity to proteins in models. They
  may also be very different functionally\, but the extent of these differe
 nces/similarities is masked by our lack of understanding on how these dive
 rgent systems work. We have developed a novel genome-wide approach to func
 tionally profile genes in trypanosomes. Direct RNAi-Fragment Sequencing (D
 RiF-Seq) robustly and sensitively measures competitive growth rates for >2
 00\,000 individual RNAi mutants in each experiment and can be used both in
  culture and in host. Quantitation of competitive growth rates shows that 
 ~50% of non-VSG genes are associated with a significant loss-of-fitness in
  vitro – suggesting an essential genome in trypanosomes similar to that 
 seen by Bar-Seq in Plasmodium. DRiF-Seq also reveals temporal hierarchy in
  gene knockdown fitness and allows comparison of fitness costs associated 
 with specific components of biological processes. Comparison with genome-s
 cale fitness datasets in Toxoplasma and Plasmodium shows conserved process
 es with differential fitness costs in Apicomplexa and Trypanosoma\, and th
 e method is sufficiently sensitive to highlight differential biology betwe
 en different trypanosome species. Epistatic interactions between specific 
 mitotic mutants and DRiF-Seq libraries suggests regulation of mitosis in t
 rypanosomes has more similarity to model systems than sequence comparisons
  might suggest.\n\nWe encourage in person attendance but the talk will als
 o be streamed via "zoom":https://zoom.us/j/91250911319?pwd=ZDlZVXhiQXI4M3V
 XZytnOEJ4bk1Hdz09
LOCATION:Seminar Room\, Tennis Court Road\, Dept of Pathology.
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