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  The overall goal of establishing Academia Sinica Cryo-EM Center (ASCEM) is to increase the energy of fundamental life science research of Taiwan and Academia Sinica via introduction of cutting-edge instruments and to assist analyzing protein structure and cellular ultrastructure for further solutions of bio-technology issues and serious disease problems.
  ASCEM hosts four instruments, including two newly purchased high-resolution cryo-EM instruments (FEI Titan Krios 300 keV and FEI Talos Arctica 200 keV) and two existing low-end cryo-EM instruments that are previously supported by Academia Sinica: FEI Tecnai G2 F20 (200 keV) in the Institute of Cellular and Organismic Biology and JEOL JEM-1400 (120 keV) in the Institute of Chemistry. The two high-resolution cryo-EM (CEM3/4) run on 24hrs/7days base and are open to other users outside of Academia Sinica while the other two lower-resolution instruments work on 8 hrs/5days base and are mainly open for users within Academia Sinica.

CEM1 is mainly for training cryo-EM beginners and negative staining, the first step of checking the quality of protein or particle samples in the total cryo-EM workflow.

CEM2 is for preliminary study of cryo-EM, to check sample conditions and to obtain a low-resolution structural model. It could also be used for cryo-tomography (CTM) and other applications such as liposome.

CEM3, equipped with Falcon detector and Volta phase plates, is for multi-purpose and include the following tasks: (i) tomography; (ii) overflow of the preliminary study samples from CEM2; (iii) screening of grids for CEM4; and (iv) collection of high quality data for structural determination (up to 4 angstrom or a little better) and publication.

CEM4, equipped with both Falcon and K2 detectors and Volta phase plates, is particularly for the studies of high-resolution structures. Preliminary data from CEM1, CEM2 and CEM3 are required to demonstrate the feasibility and quality of the sample. Biological significance and associated functional studies should also be provided to justify the need or the priority to use CEM4.

Users must pass stringent training and tests before he or she is allowed to operate an instrument independently. Accordingly, ASCEM will hold workshop annually and provide training courses non-periodically. Moreover, ASCEM collaborates with Academia Sinica Grid Computing Centre (ASGC) to provide optimized data handling, big data analysis and efficient computing over the distributed infrastructure in Academia Sinica for users. ASGC also serves as a hot backup site for all cryo-EM raw data and calculation results via a dedicated campus network connection.
  Phase I: Starting Up (2017.03 - 2019.06)

The planning and organization of ASCEM started in 2017. It was established in the early 2018 and was officially open to public in September of the same year. After unsuccessful attempts in recruiting cryo-EM experts from abroad, ASCEM decided to form its own Cryo-EM Single Particle Analysis (SPA) Service Team by training domestic professionals.

At this stage, seven Academia Sinica research fellows with structural biology background devoted themselves to ASCEM establishment, including Dr. Ming-Daw Tsai, Dr. Shang-Te Danny Hsu, Dr. Meng-Chaio Joseph Ho, and Dr. Kuen-Phon Wu from IBC, Dr. Wei-Hau Chang from IoC, Dr. Chi-Yu Fu from ICOB, and Dr. Su-Chang Tom Lin from GRC. The team members met weekly to establish operation and service workflow and to examine the effectiveness and performance of the center. As a result, a financially affordable and user-friendly, research orientated “one-stop” service was gradually shaped up, and the unique service allows the newly bought instruments, CEM3/4, to be used efficiently and to largely reduce the waiting time on the machine. The key components for the operation include a high performance data transfer system, a connection with ASGC resources for data analysis, well-trained facility managers and staffs, and a generous support from Taiwan Protein Project (TPP). Due to the funding support from Academia Sinica and TPP, ASCEM users currently only need to take care of sample preparation and data analysis, and the waiting time for the instruments is within 2 weeks in average, which is far superior to international cryo-EM centers. Moreover, the charge is only about 1/5~1/10 of abroad.

In addition to the weekly management meeting, there was a biweekly Interest Group Meeting (or User Meeting) since March 2017, organized by Dr. Gan-Guang Liou from IBC. This Meeting was aimed to create an interaction opportunity for cryo-EM users. Issues related to ASCEM policy and instruments were also open for discussion here. Non-periodical training workshop or courses were also provided for encouraging projects collaboration.

Because Academia Sinica has been highly concerned with the success of ASCEM, an evaluation was arranged about a half year after the official opening of ASCEM. The evaluation team, led by AS Vice President, Dr. Mei-Yin Chou, was formed by 3 foreign and 1 domestic cryo-EM experts. On June 6, 2019, the review was presented to AS President James C. Liao, VP Mei-Yin Chou, VP Fu-Tong Liou, Central Academic Advisory Committee, and Instrument Service Division. Overall, ASCEM obtained very positive feedback from all reviewers. They were especially impressed by that ASCEM could run with international competitiveness in such a short period, with high level publication already produced.

Phase II: Growing Up (2019.06 - today)

After the 1st evaluation, ASCEM set three goals for the 2nd phase based on the advices of reviewers and Academia Sinica leaders: to stabilize the center operation, to solve important scientific issues, and to develop Electron Cryo-EM Tomography (ECT). The establishment of ECT service is in response to a new trend and needs in life science research and for bridging structural biology into cell biology. It will also expand the users of ASCEM and increase the usage efficiency of instruments. In addition, we have adjusted the leadership team and the operation procedures slightly. The biweekly Interest Group Meeting (or User Meeting) is changed to monthly, and the weekly internal management meeting is changed to biweekly. Due to lack of ECT experts with background in biology, ASCEM hopes to see more colleagues with interest in ECT to work together with us.
Acknowledging ASECM in publications
  Users should acknowledge support provided by center in any resulting publications as: Academia Sinica Cryo-EM Center (Grant No. AS-CFII-108-110) and Taiwan Protein Project (Grant No. AS-KPQ-109-TPP2 and/or AS-KPQ-105-TPP).

Please also include ASGC (Academia Sinica Grid-computing Center) in the acknowledgement when research outcomes that relied on ASGC resources, services or expertise are presented. For example, “This work used ASGC (Academia Sinica Grid-computing Center) Distributed Cloud resources, which is supported by Academia Sinica”. Or, simply include “ASGC (Academia Sinica Grid-computing Center)” in the list of institutes to be acknowledged.
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Contact: Ms. Hsin-Hua Lin, Academia Sinica CryoEM Center   Email:cryoem@gate.sinica.edu.tw

No. 128, Sect. 2, Academia Rd., Nankang, Taipei 115, Taiwan (R.O.C.)      TEL:(02) 27855696 #3020

(Lab) B2-I04 (Interdisciplinary Sci. & Tech. Building), No. 28, Ln. 70, Sec. 2, Academia Rd., Nankang, Taipei 115, Taiwan (R.O.C.)

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