New heads of units for EMBL Heidelberg Council ... - EMBL Grenoble

EMBL&cetera • August 2007 • page 7“ReinforcingEMBL’s footprint onthe chemicalbiology map”Researchers at EMBL have just started thefirst phase of a three-year initiative aimedat translating basic research into new anti-cancerdrugs and transferring technology fromEMBL into a new start-up company.A Go-Bio/BioChance Plus award of €3.4mfrom the BMBF will focus on translationalresearch and is coordinated by Joe Lewis, headof the Chemical Biology Core Facility, who issupported by George Reid of the FrankGannon Group in Heidelberg. This grantenables basic biologists, medicinal chemistsand computational chemists to pursue leadsthat have promise as anti-cancer drugs and toenhance the expertise that is currently inhouse.The most promising series of small moleculeswill be tested for efficacy in vivo usingmodels of different tumours, such asleukeamias, lung cancer and breast cancer.This project-driven research will integratechemistry into biology and raise the profile ofEMBL in its chemical biology efforts.The project depends on industry experiencedtalent; Jochen Ammen has just beenhired from a large pharmaceutical company tolead a team of medicinal chemists who areworking in labs temporarily rented from BASFin Ludwigshafen. They have just started tosynthesise the first variations of compoundsidentified in the EMBL Chemical Biology CoreFacility from screens inspired by the basicresearch of the Gannon and Conti laboratories.The Go-Bio project pursues two differentavenues: one is to inhibit Aurora kinases, a keyplayer in many tumours, through a novelallosteric binding site. The details of this siteOne of EMBL’s current aims is to expandfurther into the growing field of chemicalbiology. Here’s how we’re doing it...were uncovered by Elena Conti’s group andIsabelle Vernos’ group at EMBL Heidelberg.The other projects under development arisefrom ground-breaking discoveries by theGannon group in transcriptional cycling. Thecomplexity of these events suggested that it maybe possible to modulate estrogen signalling, akey factor in the development of breast cancer,not only with small molecules that directly interactwith ER-α, but also with small moleculesthat target other processes involved in transcription.Not all of this project will be done at EMBL:after an initial period of one year, part of theBMBF funding and the staff will be transferredto ELARA Pharmaceutical GmbH, a start-upcompany that was founded by Joe, George,Frank Gannon and others last year, for furtherdevelopment.EMBL Heidelberg will eventually have a dedicatedchemistry infrastructure to reflect thegrowing importance of the field in molecularbiology.“Small molecule screening has lately movedaway from pharma and industry into academiclabs,” explains Joe. “Its methods are becomingmore amenable to basic research groups, and sochemical biology is becoming increasinglyimportant to the work done at EMBL. With this,the Go-Bio project will be a great demonstrationthat basic research can address the expectationof society that new medicines can and will bedeveloped from basic biology.”“Through creating a project-led, seamlessflow from basic research through preclinicaldevelopment, we will increase the opportunitiesfor drugable targets and offer greater prospectsfor the treatment of cancer,” says George.New participant in joint chemical biology core facilityHeidelberg University is set to join theDKFZ/EMBL Chemical Biology CoreFacility, resulting in an even better serviceto help scientists develop new researchtools.The three-and-a-half-year old facility,based at EMBL, offers researchers the abilityto screen small molecules and identifybiological inhibitors and drug precursors.The new set-up will pay off not only by providingexcellent research possibilities butalso by benefitting each of the three institutesby attracting scientists and improvingexternal funding for medicinal chemistry.“It adds significant value by creating possibilitiesfor successful technology transfer orfor our spin-off companies such as ElaraPharmaceuticals,” commented MartinRaditsch of EMBLEM, the commercial armof EMBL.Planting the seedSynergy is a word often misused in biology.The 20-22 June EMBO workshop at EMBLHamburg, “Integrated Approaches inStructural Enzymology: The Chemistryand Biochemistry of Catalysis byBiological Systems”, was excellent proofthat true synergy is to be obtained at theinterfaces between scientific disciplines.The workshop, which aimed to give anoverall perspective on current concepts onthe chemistry and biology of enzyme function,brought together about 100 crystallographers,NMR specialists, enzymologists,biochemists and computational biologistsfor sessions on drug design, molecularmotors, new technologies, the origin of thecatalytic power of active sites and the designof new biocatalysts. One highlight amongthe exceptional presentations by high-rankingspeakers was Vern Schramm (AlbertEinstein College, NY), who mapped indetail the transition-state structure of smallmolecule substrates in enzymatic reactionssuch as for the enzyme purine nucleosidephosphorylase. This provides powerfulmechanistic insights into enzymology thatcan be used to aid rational design of substratecompetitive inhibitors with very highpotencies. Using this approach, his lab hasdeveloped a new class of inhibitors that arecurrently being tested in clinical trialsagainst T-cell malignancies.The response from the participants wasvery positive. Extensive discussions andextremely productive poster sessions complementedthe lectures. The idea of integratedmultidisciplinary approaches for anin-depth investigation of enzymes washighly appreciated by the audience.Specific emphasis was given to the applicationand the use of information for the elucidationof structure function relationships.There was general agreement from thecurrent participants that having such aworkshop on a yearly basis could provide aplatform for fruitful discussions, networkingand future collaborations and reinforceEMBL’s footprint on the chemical biologymap.Organising committee:Andrea Schmidt and Victor Lamzin(EMBL Hamburg), Joe Lewis (EMBLHeidelberg), Rikkert Wierenga (Uni. ofOulu), Andrea Mattevi (Uni. of Pavia),Hartmuth Oschkinat (FMP Berlin)