長庚大學學生出席國際會議報告書. 填寫日期 : 2016 年 08 月 01 日 系所及年級 生醫所博士班五年級 Archan Chakraborty 學號 D /07/13 至 2016/07/17 Orlando, Florida, USA

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1 附表六 長庚大學學生出席國際會議報告書 報告人姓名 會議期間 會議地點 填寫日期 : 2016 年 08 月 01 日 系所及年級 生醫所博士班五年級 Archan Chakraborty 學號 D /07/13 至 2016/07/17 Orlando, Florida, USA 核定補助日期 105 年 5 月 25 日 會議名稱 ( 中文 ) ( 英文 ) The Allied Genetics Conference (TAGC) 發表論文題目 ( 中文 ) ( 請附論文全文 ) ( 英文 ) Proteomic analysis of CTP synthase filaments in Drosophila De novo pyrimidine pathway utilizes CTP synthase (CTPsyn) as a rate-limiting enzyme for the biosynthesis of cytidine triphosphate (CTP). In nutrient depletion conditions, CTPsyn assembles into filamentary structures. This self-assembly, higher ordered structure suggests a key regulation of metabolism in the cell. The question that allures us the most is why this metabolic enzyme needs to form filaments? Is this an easy way to tune in the production of CTP whenever required? There has been already an ongoing debate on 論文內容摘要 whether this specialized structure is catalytically active or just a protein aggregate. Our lab has demonstrated that CTPsyn filaments are regulated by ubiquitination and support S phase during endocycles in follicle cells. Recently it has been reported that IMPHD2 co-localizes with the CTPsyn filaments in human cell lines. Moreover, in Drosophila, the DAck was also found to co-localize with the CTPsyn filaments in the germ cells where the structure maintains the integrity of cell membrane through phospholipid production. It is possible that the structure has different associ-

2 ated proteins at different physiological conditions, which can regulate their enzymatic activity. Therefore, it would be very important to identify the structural components of these filaments and elucidate their activities. Here we use a system in which CTPsyn is tagged to genetically engineered peroxidases, APEX2. APEX2 can oxidize the biotin-phenol to generate a very short-lived biotin-phenoxyl radical, which covalently tags the endogenous proteins adjacent to the APEX2 protein. Using the above approach we have successfully labeled the CTP synthase filaments in the live Drosophila ovary tissues with biotin and have successfully identified the biotinylated targets of the filament structure in germline cells, and in the follicle cells using mass spectrometry. Currently we are examining the involvement of the candidates in CTPsyn filament formation using co-localization or knockdown approaches. 一 報告內容請另頁撰寫, 以 A4 標楷 12 橫寫 直式列印, 內容包括 : ( 一 ) 參加會議經過 ( 二 ) 與會心得 1. 以獲取專業新知為主, 其他新知, 例如人生經歷等為輔 2. 新知需提示來源 ( 含機構 研究者 等 ), 若有其他相同觀點之研究團隊亦可一併納入, 以利有興趣者查詢 ( 三 ) 建議 ( 四 ) 攜回資料名稱與內容 ( 五 ) 其他二 系所安排口頭心得報告時間 : 年 月 日 ( 未安排原因 : ) 研發長 所長 指導教授 報告人 學生出席國際會議報告書及網路刊載由研發處備存辦理

3 長庚大學出國會議報告書 4 th year Ph.D student at Graduate Institute of Biomedical Sciences D Archan Chakraborty The meeting was organized by Genetic Society of America (GSA) at Orlando, Florida. This is the 100 th year of GSA and it was the first time that all the seven genetic communities (C.elegans, Ciliate, Drosophila, Mouse, Yeast, Zebrafish and Population Evolutionary & Quantitative Genetics) held their meeting together. It was an extraordinary event with an objective to increase effective communication among the scientific communities and encourage students, young researchers and scientists to work as a unified genetics community for advancing the field of genetics. I was very excited to see Francis Collins at the meeting, who is the current head of National Institute of Health (NIH), USA. His talk aspired about Accelerating Insights from Basic Genetics. It was a huge meeting with 1713 posters presenters across the globe. I am very thankful to Chang Gung University for giving me this opportunity to attend this amazing meeting and meet renowned scientists among different model organism communities. It was very encouraging to present a poster at the meeting. Many scientists stood by my poster and gave me valuable suggestions for my future work. Below I would like to write about few scientific sessions which I took keen interest to listen while enjoying the scientific ambience.

4 1. Organizing the contraction that changes the tissue shape -by Adam Martin, MIT. The process of constriction at the apical side of the polarized cell is known as apical constriction. This phenomenon is a morphogenetic event which is involved in cell invagination, epithelial-mesenchymal transition and the formation of neural tube. During gastrulation in drosophila, apical constriction is required for the formation of ventral furrow. The dynamic actomysin network at the apical side generates force to change tissue shape. Snail and twist are two transcription factors that trigger the formation of ventral furrow. Twist expression can activate Rho1 (RhoA) GTPase and heterotrimeric G-proteins. They found that during apical constriction, the ROCK (Rho-A kinase) is enriched at the center of the apical cortex together with actin filament pointed ends and myosin and decreases with apical junction. They have identified a RhoA GDP which is essential for establishing the polarity of ROCK at the apical cortex. 2. GPCR receptor Rickets delays the border cell migration in Drosophila ovaries. - by Lauren Anllo, Princeton University Border cell cluster in drosophila ovaries is a good system for studying the coordinated cell movement. They found that bolder cells having mutant G-protein coupled receptor (GPCR), Rickets (rk), have defects in migration and coordinated movement. In rk mutant border cells, E-cadherin is mislocalized to the outer periphery instead of lo-

5 calizing at the cell adhesion junction. This mislocalization only occurs in mosaic clones and not in full mutant border cell cluster. Higher the mosaic clones, the degree of migration defect was also higher. 3. Mono - ubiquitination of Dronc functions in both apoptotic and non-apoptotic pathways by Hatem Elif Kamber Kaya Drosophila Dronc is an ortholog for caspase-9 and 2. The N terminal CARD domain is responsible for its uptake into apoptosome and its activation. Dronc can also help in the 360 degree rotation of the male genitalia. They found that in living cells Dronc is mono-ubiquitinated at K78 in the CARD domain which prevents it from activation in the apoptosomes. It prevents the binding of DARK to Dronc. Moreover the non apoptotic functions of Dronc are also inhibited by this mono ubiquitination. 4. The niche ligand receptor directly orients the spindle in drosophila male germline stem cells - by Cui Chen, University of Michigan They found that the Upd (upaired) ligand, Dome, can directly interact with the plus end of the microtubule binding protein Eb1 in the GSC to orient the spindle towards the niche to promote asymmetric division. The downstream JAK-STAT pathway is not required for the spindle orientation. Dome and Eb1 pull the spindle towards the niche. This is the way by which niche can govern the asymmetric division of GSC.

6 5. Mutation in fat2 uncouples tissue elongation from global tissue rotation in drosophila -by Franziska Aurich, University of Dresden. In drosophila ovaries, global tissue rotation of egg chambers couples with tissue elongation. Rotation of egg chamber is due to the circumferential alignment of actin filaments and extracellular fibers. The atypical cadherin Fat2 is required for egg chamber elongation, rotation, and the circumferential alignment of actin filaments and extracellular fibers. The localization of Fat2 protein at the basal side of follicle cells is planar polarized. Fat2 protein is enriched on cell junctions oriented parallel to the long axis of the egg chamber. The rotation is restricted in egg chambers expressing a truncated fat2 protein as the location of this mutant protein is not plane polarized. 6. Modelling Intellectual Disability Disorders in Drosophila - from Genes to Functional Modules and Clinical Applications - by Annette Schenck, Radboud university medical center. Intellectual Disability (ID) disorders are, due to their high frequency and lifetime long expenses, the biggest unmet challenge in clinical genetics and among the largest cost factors of health care in Western countries. ID disorders are largely monogenic, and disease gene identification over the past decade has been highly successful. More than 800 causative genes ( ID genes ) have been reported, providing unique stepping stones into the molecular basis of cognition. In a screen for ID genes, 100 novel ha-

7 bituation genes were identified. One key important pathway was RAS/RAF pathway. In many cases of ID disorders, RAS/MAPK pathway shows and increased activity. Moreover they also identified PTPNII/SOSI regulate habituation in cholinergic neurons. 四 攜回資料名稱與內容 2016 TAGC Program Book