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 M3//EN
VERSION:2.0
CALSCALE:GREGORIAN
METHOD:PUBLISH
BEGIN:VEVENT
DTSTAMP:20140205T125125Z
DTSTART:20140205T130000Z
DTEND:20140205T140000Z
SUMMARY:Molecular Networks and the Mechanism of Action of Anticancer Agen
 ts
UID:{http://www.columbasystems.com/customers/uom/gpp/eventid/}bdr-hr3dvdr
 a-3mm7kl
DESCRIPTION:This seminar is part of the Special Seminar Series\n\n\nBiolo
 gically active chemical compounds produce complex molecular responses al
 ready at the cellular levels. The majority of compounds bind to several 
 proteins: proteins of the cognate target class\, those for which the com
 pound was designed\, but often also proteins bearing completely differen
 t folds. These proteins affect different pathways and cellular processes
 . While we usually monitor the net outcome of all these interactions in 
 terms of selected biological readouts we are mostly oblivious of the int
 ricacies that occur at the molecular level. We have investigated the mec
 hanism of action of several compounds in clinical use against cancer\, m
 ostly of hematological origin. We used a number of approaches\, ideally 
 in parallel: 1)  chemical proteomics (affinity purifications using immob
 ilized drug matrices followed by mass spectrometry)\, 2) chemical geneti
 cs (random mutagenesis of genome of near-haploid CML cells)\, 3) functio
 nal proteomics (affinity purification / mass spectrometry)\, 4) transcri
 ptional profiling \, 5) phosphoproteomics (where appropriate)\, 6) compu
 tational network analysis and modeling (protein-protein\, drug-protein\,
  protein-disease a.s.o.)\,  and 7) validation by focused gene inactivati
 on (RNAi and genome editing). We try to obtain a detailed picture of the
  actual molecular events and requirements of the drugs under investigati
 on. Using this integrated approach we have identified: 1) new targets fo
 r known drugs\, 2) previously unknown mechanisms of drug resistance\, 3)
  “effector” genes for the compounds (genes required for the drug to exer
 t its action)\, 4) mechanisms of synergy between compounds and in a few 
 cases 5) new medical use of existing drugs. We hope that systematic adop
 tion of this more rigorous and “systems-level” characterization of chemi
 cal entities will help understanding the biology of drug action better a
 nd allow the development of improved drugs. We also believe it should he
 lp the community in rationalizing patient stratification\, thus increasi
 ng the efficacy of clinical trials and reduce unwanted side effects\, bu
 t also contribute to the employment of mechanism-based combination thera
 py with existing drugs.\nBürckstümmer\, T. et al (2013). A reversible ge
 ne trap collection empowers haploid genetics in human cells. Nat Methods
  10\, 965-971.\n\nHost:Douglas Kell\, MIB
STATUS:TENTATIVE
TRANSP:TRANSPARENT
CLASS:PUBLIC
LOCATION:MIB Lecture Theatre\, Manchester Institute of Biotechnology - Jo
 hn Garside Building\, Manchester
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