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Mechanism study of early neurodevelopment and neurological disorders mediated via DNA damage response, protein phosphorylation and RNA methylation
China (IFMSA-China) - Peking Union Medical College, Beijing
Department of Pathology
Prof. Wei-min TONG
Dr. Wei-min TONG, Professor & Dr. Yamei NIU, Associate Professor
Type of Research Project
- Basic science
What is the background of the project?
Biological processes in brain are extremely complex and require elegant fine-tuning at multiple levels. Comprehensive understanding that how it is regulated will greatly accelerate the diagnosis and therapeutics of neurological diseases. Firstly, prompt and proper DNA damage repair against various endogenous and exogenous DNA damage is necessary to maintain the genome stability. Neurological disorders caused by dysfunction of DNA repair factors have been determined clinically, but related mechanism remains largely unknown. Secondly, reversible phosphorylation is an important protein modification determining their protein activities or substrate specificities. Therefore, unbalanced phosphorylation levels will have severe effect on a series of biological processes, including neurodevelopment. Thirdly, with the rapid development of RNA biology, the roles of RNA in brain development have been revealed to be indispensable. m6A is a novel and evolutionally conserved RNA epigenetic marker found in various kinds of RNAs. In spite of its ubiquitous expression, its biological functions in brain are unclear yet.
What is the aim of the project?
Based on animal models, cellular studies, and combining with clinical samples analysis, we aim to identify the functions of DNA (Deoxyribonucleic acid) repair factors in in medulloblastoma and glioma.
What techniques and methods are used?
Molecular cloning, PCR (Polymerase Chain Reaction), SDS-PAGE (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis), Western blot, Immunohistochemistry, FISH (Fluorescence in situ Hybridization), Immunofluorescence, cell culture, transfection, RT-PCR (Reverse Transcription PCR Polymerase Chain Reaction), FACS (Fluorescence Activated Cell Sorting), animal works and so on. All above are basic techniques in a team working in the field of molecular biology, cellular biology and pathology. Thus, they will be necessary throughout the project.
What is the role of the student?
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
After one-month training, the student should be able to master the following techniques: bacteria culture, cell culture, PCR, molecular cloning and RNA isolation. In addition, they may also be able to perform the following experiments under supervision: mouse dissection, RT-PCR, Western Blot, immunohistochemistry, and immunofluorescence. Also, the student should be able to have the basic ability of troubleshooting with all the techniques mentioned above, and the ability of analyze both the positive and negative results.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster - The student will prepare a presentation - No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
English proficiency is essential. Besides, knowledge of molecular biology and cellular biology are necessary. Experience in bench work will be preferred.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Students in biomedical fields
- Chang MQ#; Lv HY#; Zhang WL; Ma CH; He X; Zhao SL; Zhang ZW; Zeng Y-X; Song SH; Niu YM*; Tong W-M*. 2017 Regionspecific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain. Open Biol. 7:170166.
- Li; R.; Yang; Y.G.; Gao; Y.; Wang; Z.Q.; and Tong; W.M*. (2012). A distinct response to endogenous DNA damage in the development of Nbs1-deficient cortical neurons. Cell research 22; 859-872.
- Zheng G#; Dahl JA#; Niu Y#; Fedorcsak P; Huang CM; Li CJ; Vågbø CB; Shi Y; Wang WL; Song SH; Lu Z; Bosmans RP; Dai Q; Hao YJ; Yang X; Zhao WM; Tong W-M; Wang XJ; Bogdan F; Furu K; Fu Y; Jia G; Zhao X; Liu J; Krokan HE; Klungland A*; Yang YG*; He C*. (2013). ALKBH5 is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility. Molecular Cell 49; 1-12. (#Co-first authors)
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