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      • An Intercultural Experiment to Build Life Science Innovation in Korea

        Ulf Nehrbass 과학기술정책연구원 2012 STI Policy Review Vol.3 No.1

        The establishment of Institut Pasteur Korea (IP-K) has been an intercultural experiment, which transplanted a French research organization with many foreign researchers into Korea to grow a new institution as a long-term collaboration. The Mission of the newly founded institute has been to develop more effective ways of generating value with basic life science research in the face of a world-wide Pharma crisis. The challenges have been i.) to invent new technologies and approaches in drug discovery, ii.) to convince the Korean stakeholders of their inherent value, iii.) to induce Pharma industry to adopt the new technologies and iv.) to create a context in the Korean R&D landscape where the new institute could contribute tangible benefits. If Institut Pasteur Korea has succeeded in all counts, then due to a somewhat skewed and unlikely set of cultural complementarities between Korea and France. The abstract and conceptual French approach was matched by Korean pragmatism, linearity and relentless improvement towards the defined development goal. IP-K has become an example for innovation made in Korea, which is now re-imported into Europe. As the project could arguably not have succeeded in either partner county alone, it highlights the benefits of longterm, in depth international collaborations.

      • Detection of melanoma using antibody-conjugated quantum dots in a coculture model for high-throughput screening system

        Kim, Myung Jin,Lee, Ji Young,Nehrbass, Ulf,Song, Rita,Choi, Youngseon The Royal Society of Chemistry 2012 The Analyst Vol.137 No.6

        <P>We proposed an effective strategy for evaluating the targeting specificity of an antibody-conjugated quantum dot (QD) nanoprobe in a coculture system mimicking an <I>in vivo</I>-like tumor microenvironment in which cancer cells grow with normal cells. Analysis of the images was performed with automated confocal microscopy. We have employed a melanoma–melanocyte coculture model to assess the specific binding of QDs conjugated with melanoma antibodies. Conjugation of antibodies to the QD significantly improved the melanoma specificity, while unconjugated antibody alone suffered from non-specific binding to melanocytes. Concentration-dependent binding and competitive inhibition studies with QD–antibody conjugates reproducibly proved the specificity to melanoma cells against melanocytes. The specificity and targeting efficiency of nanoprobes evaluated in a simple coculture model may provide a reasonable assessment for the <I>in vitro</I> diagnosis of early stage melanoma development before <I>in vivo</I> studies. Further, a rapid and sensitive cancer cell detection system demonstrated herein may allow for the development of high-throughput screening platforms for early cancer diagnosis and anti-cancer therapeutics.</P> <P>Graphic Abstract</P><P>Specific targeting to melanoma in the presence of melanocytes was demonstrated using antibody-conjugated quantum dots (QDs) with improved binding efficiency for potential high-throughput screening application. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2an16013g'> </P>

      • Integrase interactor 1 (Ini1/hSNF5) is a repressor of basal human immunodeficiency virus type 1 promoter activity

        Boese, Annette,Sommer, Peter,Holzer, Daniela,Maier, Reinhard,Nehrbass, Ulf Microbiology Society 2009 The Journal of general virology Vol.90 No.10

        <P>Integrase interactor 1 (Ini1/hSNF5/BAF47/SMARCB1), the core subunit of the ATP-dependent chromatin-remodelling complex SWI/SNF, is a cellular interaction partner of the human immunodeficiency virus type 1 (HIV-1) integrase. Ini1/hSNF5 is recruited to HIV-1 pre-integration complexes before nuclear migration, suggesting a function in the integration process itself or a contribution to the preferential selection of transcriptionally active genes as integration sites of HIV-1. More recent evidence indicates, however, that, whilst Ini1/hSNF5 is dispensable for HIV-1 transduction per se, it may have an inhibitory effect on the early steps of HIV-1 replication but facilitates proviral transcription by enhancing Tat function. These partially contradictory observations prompted an investigation of the immediate and long-term effects of Ini1/hSNF5 depletion on the basal transcriptional potential of the virus promoter. Using small interfering RNAs, it was shown that Ini1/hSNF5-containing SWI/SNF complexes mediate transcriptional repression of the basal activity of the integrated HIV-1 long terminal repeat. Transient depletion of Ini1/hSNF5 during integration was accompanied by an early boost of HIV-1 replication. After the reappearance of Ini1/hSNF5, expression levels decreased and this was associated with increased levels of histone methylation at the virus promoter in the long term, indicative of epigenetic gene silencing. These results demonstrate the opposing effects of Ini1/hSNF5-containing SWI/SNF complexes on basal and Tat-dependent transcriptional activity of the HIV-1 promoter. It is proposed that Ini1/hSNF5 may be recruited to the HIV-1 pre-integration complex to initiate, immediately after integration, one of two mutually exclusive transcription programmes, namely post-integration latency or high-level, Tat-dependent gene expression.</P>

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