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SUMMARY:The Druggable Transcriptome Project: From Chemical Probes to Preci
 sion Medicines   - Matthew Disney - Scripps Research Institute
DTSTART:20250401T133000Z
DTEND:20250401T143000Z
UID:TALK229771@talks.cam.ac.uk
CONTACT:Xani Thorman
DESCRIPTION:A scientific challenge is to understand biological pathways an
 d to exploit the targets within them for therapeutic development.  Coding 
 and non-coding RNAs both directly cause disease\, whether by mutation or a
 berrant expression.  Akin to proteins\, RNA structure often dictates its f
 unction in health or dysfunction in disease.  RNA\, however\, is generally
  not considered a target for small molecule chemical probes and lead medic
 ines\, despite its immense potential.  The focus of our research program i
 s to uncover fundamental principles that govern the molecular recognition 
 of RNA structures by small molecules to enable design of chemical probes t
 hat targeting disease relevant RNA structures to perturb and study their f
 unction.  \n \nI will describe using evolutionary principles to identify m
 olecular recognition patterns between small molecules and RNA structures b
 y studying the binding of RNA fold libraries to small molecule libraries. 
  These interactions are computationally mined across the human transcripto
 me to define cellular RNAs with targetable structure.  Such an approach ha
 s afforded bioactive interactions that have uncovered new biology\, where 
 the small molecules bind to functional structures within a target RNA.  We
  have devised a strategy to imbue biologically silent RNA-small molecule i
 nteractions with cellular activity.  Chimeras comprising an inactive small
  molecule and ribonuclease recruiter trigger targeted degradation of disea
 se-causing RNAs.  These degraders affect the biology of RNA in specific wa
 ys in cells and in mouse models of various diseases and can rationally rep
 rogram protein-targeted medicines for RNA.  Lastly\, we have recently devi
 sed unbiased transcriptome wide approaches to define the RNA bound by smal
 l molecules is live cells.  This allows us to study the RNA targets that a
 re bound by small molecules\, the selectivity of these interactions\, and 
 ways in which compounds of various types can modulate disease biology.
LOCATION:Department of Chemistry\, Cambridge\, Pfizer lecture theatre
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