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SUMMARY:Synthetic control of peptide and protein architectures - Professor
  Yu Heng Lau\, The University of Sydney
DTSTART:20230203T160000Z
DTEND:20230203T170000Z
UID:TALK193537@talks.cam.ac.uk
CONTACT:111982
DESCRIPTION:Synthetic chemistry and synthetic biology offer complementary 
 tools for manipulating the 3D architecture and function of biomacromolecul
 es. In this seminar\, I will outline two different projects that exemplify
  our hybrid approach to controlling peptide and protein architectures\, ma
 king fundamental discoveries that have diverse potential applications from
  catalysis to cancer therapy.\nThe first project involves the study of enc
 apsulins\, self-assembling protein cages that act as organelles in bacteri
 a. There is substantial interest in using encapsulins as nanoreactors for 
 hosting custom catalytic reactions\, but remarkably little is known about 
 their basic molecular properties\, such as the fundamental dynamics of how
  substrates and products diffuse into and out of these cages. Using a comb
 ination of single particle cryo-EM\, molecular dynamics\, and stopped flow
  kinetics to study a library of designed cage variants\, we uncover the co
 mplex interplay of factors that determines how these cages act as selectiv
 ity filters in their roles as organelles and catalytic nanoreactors.\nThe 
 second project involves the control of peptide conformation\, using chemic
 al cyclisation to develop inhibitory probes for studying protein targets i
 mplicated in cancer. We have developed cyclic peptides that can target can
 cers that are ‘ALT-positive’ – a term that accounts for 10-15% of al
 l cancers\, describing cells that use a non-canonical telomere extension p
 athway to achieve immortality. I will outline the discovery of peptide inh
 ibitors with nanomolar affinity that disrupt FANCM-BTR\, a key protein-pro
 tein interaction that regulates the proliferation of ALT-positive cancers\
 , along with promising results from cellular assays on selected hits.\n
LOCATION:Dept of Chemistry\, Wolfson Lecture Theatre 
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