Recently,the appraisal meeting on International Scientificand Technological Project,themed at Cloning of Magnetosome Gene Cluster for Tumor-targeting Therapy,undertaken by SDU was held.Professor Wang Chengfeng,leaderof the appraisal group and chief physician of Cancer Hospital Chinese Academy of Medical Sciences,and experts from scientificinstitutions and biomedical enterprises attended the meeting.
At the meeting,the appraisal group listened to the project report made by project leader Professor Fu Jun from State Key Laboratory of Microbial Technology (Microbial Technology Institute),reviewed appraisal-related materials,inquired about and discussed on relevant issues.Finally they came to conclusion that the project could be approved as it had met all the standards provided by Mission Contract.The final appraisal results of seven assessment experts were all "excellent".
The appraisal meeting was organized by the Department of Science and Technology of Shandong Province which was entrusted by Department of International Cooperation (Office of Hong Kong, Macao and Taiwan Affairs) of Ministry of Science and Technology PRC.Liu Chunlin, Associate Consultant-Director of Scientific Cooperation Section of the Department of Science and Technology of Shandong Province attended the meeting and delivered a speech,hoping that the group members of the project could forge closer and more effective cooperation with present experts and accomplish more innovative scientific projects.Liu Quanfen,deputy director of Project Management Office of Department of Science and Technology Management,SDU,chaired the meeting.
The project has been accomplished by the joint efforts from the State Key Laboratory of Microbial Technology of SDU,Helmholtz Centre for Infection Research (Germany),Biotechnology Center of Technische Universität Dresden (Germany) and Institute of Microbiology of the Mediterranean (France).The aim of this study is to explore a novel strategy for cancer therapy and develop corresponding methodologies.This new strategy is based on screening and genetic modification of tumour colonization bacteria. Addition to the property of tumour repression,the gene clusters which synthesize cytotoxic compounds and magnetosome are horizontally transferred in the bacteria for further inhibiting of the tumour by chemical therapy or magnetic hyperthermia.The study is conducted in four aspects: first,for efficient cloning of gene clusters which synthesize cytotoxic compounds and magnetosome,in vitro DNA annealing based on the exonuclease and in vivo homologous recombination based on the RecET have been combined to create a novel method which is termed ExoCET (Exonuclease combined with RecET recombination).Using this new method,DNA fragment larger than 100kb can be directly cloned from original DNA preparation.A 50kb plasmid can be assembled in one step from 20 smaller DNA fragments.The Red system and the RecET system have also been integrated into oneE.colihost and the cloning vectors and DNA cassettes have been standardized to establish an efficient technology platform for gene cluster direct cloning and heterologous expression.Second,the 81kb and 40kb magnetosome gene cluster from the Desulfovibrio magneticusRS-1 and the Magnetofaba australisIT-1 are obtained from ExoCET DNA assembling.After modification of the plasmids,the gene clusters were conjugated into the heterologous host Rhodospirillum rubrumand integrated into the its genome by transposition.Third,four gene clusters for cytotoxic compound synthesis have been cloned and heterologous expressed.The gene clusters are epothilones,disorazoles,salinomycin and thailandepsins which are 56kb,58kb,106kb and 40kb respectively.Fourth,Heterologous expression of glidobactins and lumimides inE. coliNissle1917 has shown tumour repression effect.
The project has applied for two Chinese patents and one international patent.It brought about the publication of nine SCI papers,among which 8 are co-written with foreign researchers.During its implementation,two professors of partner institutions were honored as SDU guest professors; SDU has sent doctoral and post-doctoral students to work in German laboratories for many times and four international seminars were co-held.The project,a good example of international cooperation,strengthened long-standing cooperation with foreign partners and contributed to even closer international sci-tech cooperation.
Translated by Sun Yangyang
Edited by Che Huiqing, Zhang Xinyuan