Developme（略）tracers f（略）of Sigma1（略）in the Hu（略）

Development of Radiotracers for Imaging of Sigma1 Receptors in the Human Brain

项目来源

德（略）基（略）F（略）

项目主持人

P（略）e（略）r（略）.（略）r（略）t（略）b（略）;（略）o（略）s（略）D（略）B（略）h（略）（略）s（略）

项目受资助机构

未（略）

项目编号

3（略）2（略）

立项年度

2（略）

立项时间

未（略）

研究期限

未（略）（略）

项目级别

国（略）

受资助金额

0（略）欧（略）

学科

未（略）

学科代码

未（略）

基金类别

S（略）b（略）i（略）n

关键词

未（略）

参与者

P（略）e（略）r（略）.（略）r（略）t（略）b（略）;（略）f（略）o（略）r（略）e（略）a（略）W（略）c（略）r（略）s（略）（略）（略）e（略）r（略）

参与机构

未（略）

项目标书摘要：Di（略）eptoren s（略）n neuen A（略）bei der m（略）armakolog（略）andlung v（略）denen Hir（略）en dar. V（略）terschied（略）n der Sig（略）en wird i（略） den Sigm（略）en größer（略） beigemes（略）uchungen （略）Rezeptore（略）ronen-Emi（略）graphie (（略）inzelphot（略）ons- Comp（略）phie (SPE（略）einen Bei（略）eisten, d（略）irkungen （略）gma-Rezep（略）en Neurot（略）ystemen i（略）sser zu v（略）ie neuen （略）n diese f（略）n Wechsel（略）rlauben e（略） Diagnost（略）erkrankun（略） Entwickl（略）herapeuti（略）pte. Gege（略）d keine R（略）für PET o（略）ür die kl（略）endung zu（略）ung von S（略）toren ver（略）er den vi（略）iedenen s（略）n Klassen（略）-Rezeptor（略）eten die （略）dine, die（略）zten Jahr（略）nen der A（略）r entwick（略） das best（略）l hinsich（略）ezeptoraf（略） der Sele（略）genüber d（略）ezeptoren（略）n Hirnrez（略）sierend a（略）rbeiten w（略）halogenie（略）e synthet（略）bezüglich（略）ptorbindu（略）aften cha（略）t. Diejen（略）dungen mi（略）ten Affin（略）besten Se（略）n werden （略）iomarkier（略）, 123I un（略） gewählt.（略）Präkursor（略）ür diesen（略）hetisiert（略）rungsvors（略）arbeitet.（略）mente wer（略）führt, um（略）teilung u（略）ptorbindu（略）n Radiotr（略）o zu unte（略）e verschi（略）aben werd（略） Kooperat（略）deutscher（略）ünster un（略）und eines（略）en Partne（略）durchgefü（略）letztgena（略）er durch （略）sche Wiss（略）sellschaf（略）nanziell （略） wird. Zu（略）st ist es（略）es Projek（略）basierend（略）iperidin-（略）Radiotrac（略）r Affinit（略）ktivität （略）Rezeptore（略）keln. Ihr（略）für die b（略）Dartellun（略）nd SPECT （略）rexperime（略）ucht.

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1.2009 Final Report

《》
2009年
报告

The Cold Spring Harbor Laboratory practical course"Eukaryotlcs Gene Expression"was designed for 16 students,who were selected based on their applications.The participants showed a diverse scientific background and came from various labs,from Europe(Germany,Denmark,Finland,Czech Republic and Portugal),USA and Asia(Japan)thus providing an International atmosphere.The course was organized and supervised by four Instructors,who are well established in the field of eukaryotic gene expression:Joaquin Espinosa(University of Colorado,USA),Lee Kraus(Cornell University,USA),Thomas Oelgeschläger(Marie Curie Research Institute,UK)and All Shilatifard,(Stowers Institute for Medical Research,USA).The three weeks course included practical lab courses,seminars with introductions given by the instructors about the theoretical backgrounds of the techniques used In the lab as well as dally talks by leading scientists working on eukaryotic transcription themselves.Among the invited speakers were Danny Reinberg,Eva Nogales,Sharon Dent,Frank Pugh,Robert Kingston and Dylan Taatjes.All of them gave exclusive two hour lectures on their scientific career and current lab projects.The experimental part of the course Included 18 multi-day experiments some of which will be specified In more detail below.The experiments included recombinant expression and purification of the transcriptional activator Gal-VP16,which was later on used for electorphoretic mobility shift assay(EMSA)and DNasel footprinting.Another experimental approach was the preparation of nuclear extracts of HeLa cells,which is a prerequisite for in wfro transcription assays,chromatin immunoprecipitation(ChIP)and isolation of transcription factors.The nuclear extracts were used for in vitro transcription in the presence of the activator Gal4-VP16 and for primer extension analysis.Apart from preparing nuclear extracts,further experiments with an opportunity to work with mammalian cells were given.One of those was the purification of mammalian FLAG-tagged Ash2 from HeLa cells using FLAG antibody conjugated beads.The mammalian Ash2 protein is a component of the multi subunit complex MLL and shows methyltransferase activity.Additionally,a methyltransferase assay with 3H-Adenosyl methionine as methyl group donor and histone H3 as substrate was performed to check for methyltransferase activity of Ash2.Gene silencing in HeLa cells by RNAi using transient transfection was another approach dealing with mammalian cell lines.Transcripts for Wdr5,another subunit of the mammalian MLL complex,was knocked down by sIRNA and analyzed by immunoblot analysis.Further mammalian cell line experiments involved the chromatin immunoprecipitation and DNA quantification by qPCR.Quantitative reverse transcriptase PCR(qRT-PCR)was used to analyze differences in the target gene expression level of treated and untreated cells.For the course,experts from NimbleGen(Roche)were invited to give us exclusive two days training on sample preparation,data acquisition and data analysis of the ChlP-chip technique.The genome wide transcriptional analysis tool has become one of the leading methods in recent years.In addition,nucleosomal assembly on linear DNA templates was used to investigate to chromatin remodeling activity of transcription factors as well as histone acetylation at assembled nucleosomes.Furthermore,genome wide expression level analysis of human cells under different conditions was performed by DNA microarray.For that purpose personnel of Affymetrix,a company which is expert in the field of genetic analysis,gave us an overview of the techniques and of the usage of various software tools for analyzing microarray data under professional supervision.

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