1. INTRODUCTION
The second SESAME Workshop on Structural Molecular Biology (SMB), another in the series of workshops aimed at developing the scientific program for SESAME, was held on December 6-7, 2000 at the Holiday Inn in Nicosia Cyprus. This was a follow up to the first SMB workshop, which was held in Athens on April 6-7, 2000. The full report of the Athens workshop is posted on the SESAME web site (www.sesame.org.jo). This report on the Cyprus workshop will also be placed on the SESAME web site. Between these two workshops there was one on Materials Research at SESAME held in Ankara Turkey on November 21-22, 2000. These workshops are the main activity of the SESAME Scientific Committee, cochaired
by Ercan Alp (APS/Argonne) and Herman Winick (SSRL/SLAC/Stanford University).
The hosts of the Cyprus workshop were Spyros Skourtis and Giorgios Archontis of the University of Cyprus. Support was provided by the Cyprus Research Promotion Foundation, the Cyprus Planning Bureau, the University of Cyprus, the Cyprus Institute of Neurology and Genetics, and UNESCO. With this support it was possible to invite experienced scientists from outside the Middle East. Local expenses (lodging and meals) were provided for all participants. Participants from Middle East countries provided their own airfare.
The Charge to the Workshop is given in Appendix A. Workshop participants are listed in Appendix B. One of the expected participants from the Palestinian Authority, Prof. Nael Hasan of Birzeit University, was unable to come to Cyprus due to a closing of the border crossings in Israel on the day of his departure. His contribution to the workshop is included in this report. The announcement of the workshop is given in Appendix C along with the application form which participants from SESAME member countries were asked to fill out. The preliminary workshop agenda is given in Appendix D. Appendix E is the first announcement of the Workshop/School on Bioinformatics and Structural Modeling, to be held in Istanbul on September 3-9, 2001. Appendix F is a photo of the workshop participants. A web site has been constructed by Manolis Pantos of Daresbury which contains more details on some of the workshop presentations.
The participants from SESAME member countries presented the current status of research activity in their respective countries: Samvel Haroutiunian for Armenia, Giorgios Archontis for Cyprus, Metaxia Vlassi for Greece, Nasrin Moazami for Iran, Irit Sagi for Israel, Abdulaziz Soukri for Morocco, Elsadig Eltayeb for Oman, Said Assaf for the Palestinian Authority, and Zehra Sayers for Turkey. Scientists from several of these countries already had experience with synchrotron radiation. In addition, in most of these countries there was significant research activity relevant to SMB leading to the expectation that there could be a total of many hundreds of scientists involved with SMB research at SESAME within a few years after operations begin.
Costas Iacovou from the Cyprus Planning Bureau spoke about the strong interest in research in Cyprus and the various activities already underway. He emphasized the need to form a comprehensive picture of the total financial requirements of the installation and subsequent operation of SESAME. He also announced that the government of Cyprus had invited an independent committee of international experts to evaluate the participation of Cyprus on the SESAME project and they are expecting the committee's final report.
Chris Constantinou of the Bank of Cyprus Oncology Center and Kyriakos Kyriakou of the Institute of Neurology and Genetics gave talks on their respective institutes.
There was strong emphasis on Thalassemia and its genetics, in addition to other health problems in the SESAME Region, such as malaria, cancer and infectious agents. Workshop participants visited the Oncology Center and the Institute of Neurology and Genetics on the day after the workshop.
Participants from outside the Middle East region experienced with synchrotron radiation research made presentations on the opportunities for the exploitation of SESAME in the field of SMB.
Herman Winick provided an update on the "Current Status of SESAME and its Capability for SMB Research"; Tassos Perrakis described the reality of "Macromolecular Crystallography in a Muli-National Environment"; Peter Kuhn gave a glimpse of how "High Throughput Structural Genomics Experiments at a Synchrotron Source" works; Boris Batterman and Zehra Sayers explained the theory behind "Small Angle X-ray Scattering (SAXS)" and its applications; Jim Penner-Hahn discussed "The complementarity between EXAFS and PX"; Lisa Miller presented an array of possible "Bio-medical Applications of IR micro-spectroscopy"; Irit Sagi detailed a case study of successful drug design on "Human MMP-9 with XAS and IR".
Summaries of these presentations are included in section 7 of this report.
2. EXECUTIVE SUMMARY
- Scientists from SESAME member countries Armenia, Greece, Cyprus, Israel, Iran, Morocco, Oman, Palestinian Authority, Turkey as well as those from England, Holland and the USA participated in the workshop. (See appendix B)
- The workshop served as an introduction to different applications of synchrotron radiation in SMB research for those who were not familiar with synchrotron radiation (SR). New developments in SR research were also presented and possible ways of using these in research in the member countries were discussed. (See section 7)
- The workshop provided an environment for initiation of scientific collaborations and exchange among participants. Ways for improving information flow and establishing a network were explored. (See section 4)
The Cyprus and Athens workshops evidenced a strong desire by Middle East scientists to work together to contribute to the success of SESAME in general and to its SMB program in particular. Some of these scientists already have collaborations with colleagues in Europe and the US. The workshops promoted contacts and collaborations among scientists from within the region. This was perhaps the most significant short-term impact of these workshops. Among the activities that arose, largely spontaneously from Middle East scientists, are:- Planning for a Workshop/school on Bioinformatics and Protein Modeling
- Planning for a Workshop on SMB for scientists in Algeria, Morocco, and Tunisia
- Scientific collaborations on protein structure determination
- Invitation for a Middle East scientist to work at a European synchrotron radiation facility
- Invitations for scientists from SESAME member countries to participate in the annual meeting of the Israeli Crystallography Association in June 2000
These are described in more detail in section 4 of this report.The scientists at the workshop from outside the region with experience using synchrotron radiation expressed strong interest in supporting these and other activities. This includes participating in the above workshops and schools and inviting Middle East scientists to work at their synchrotron radiation facilities.
- From the reports by scientists from SESAME member countries, it was clear that biotechnology, medical and agricultural applications were prominent activities carried out in the increasing number of research institutes of some of the countries. However, this contrasted with difficulties in some member states still working to establish research activity. Since infrastructure to support SMB research (e.g., biochemical laboratories for preparation of proteins and other samples) is not available in all SESAME member countries, it is considered very important to provide this infrastructure at SESAME, complete with scientific and technical support for users. Section 5 of this report discusses how this can be provided by an SMB Institute at the SESAME site, as described initially in the report of the Athens SMB workshop.
"The importance of this institute was emphasized in a resolution passed at the workshop which included the following:
"The biological scientists from Sesame member countries present at the Cyprus SMB workshop reaffirm and clarify the resolution passed unanimously at the Athens SMB meeting that: 'Top priority for the SMB scientific subgroup is to see a research institute established alongside Sesame for the development of SMB projects and infrastructure in the Region at the earliest possible date'. By 'alongside' we mean at the Sesame site. Experience at other SR centers around the world shows clearly that such proximity of user support facilities is critical for success." - Also included in the resolution were the following:
"The SMB subgroup of Sesame would like to ask the governments of member countries to support the establishment of networks of collaboration in research and training."
"Considering the recognition of the special need for collaboration with the PA, as included in the communiqué of the meeting of the restricted interim council, April 2000, the SMB subgroup looks forward to receiving more details for the biological sciences research institute in the PA (MEBSIR).
"MEBSIR is discussed in more detail in section 6 of this report.
3. DESCRIPTION OF SMB RELATED ACTIVITIES IN THE REGION
The report of the first SESAME SMB workshop, (see: www.sesame.org.jo) contained reports on activities in Armenia, Cyprus, Greece, Iran, Israel, Jordan, Lebanon, Morocco, the Palestinian Authority, and Turkey. Here we present an update for some SESAME member countries.
3.1 Greece - Metaxia Vlassi The National Centre for Scientific Research "DEMOKRITOS"
Greece already has a well-established SMB program. This presentation was focused on research activities related mainly to x-ray Crystallography of Macromolecules.
There are 12 Protein Crystallography groups that are based in 5 Universities and 4 Research Institutes of Greece: The Univ. of Athens, Fac. of Biology (3 groups of: Prof. E. Moudrianakis, Prof. S.J. Hamodrakas and Prof. C. Vorgias), the Agricultural Univ. of Athens, Dept. of Agricultural Biotechnology (1 group of Prof. E. Eliopoulos), the National Hellenic Research Found. in Athens (1 group of Dr. N.G. Oikonomakos), the National Centre for Sci. Res. "DEMOKRITOS" in Athens (2 groups of: Dr. M. Vlassi and Dr. I. M. Mavridis), the Hellenic Pasteur Inst. in Athens (1 group of Dr. S. J. Tzartos), the Univ. of Thessaloniki, Dept. of Physics (1 group of Prof. C. Kavounis), the Inst. of Molecular Biology & Biotechnology and the Univ. of Crete (2 groups of: Dr. K. Petratos and Prof. M. Kokkinidis) and the Univ. of Patras, Dept. of Chemistry (1 group of Prof. V. Nastopoulos). These research groups are using x-ray Crystallography as the central method for protein structure determination combined with other Biochemical and Biophysical techniques as well as Biocomputing and 3D Modelling. Two x-ray facilities appropriate for Protein Crystallography exist in Greece: One at the Centre for Crystallographic Studies of Macromolecules, (CCM) at the Inst. of Biology of the Nat. Ctr for Sci. Res, "DEMOKRITOS" in Athens. CCM is a research network consisting of 10 of the above 12 mainland research groups. It includes a state-of-the-art x-ray system comprising a Rigaku RU-H3R belt-drive rotating anode generator and an R-AXIS IV dual Image Plate detector as well as with a JASCO J-715 Circular Dichroism Spectrophotometer.
The second X-ray system is shared between the University of Crete and the Institute of Molecular Biology and Biotechnology in Heraklion-Crete. It consists of a Rigaku RU-H3R belt-drive rotating anode generator combined with a Mar300 Image Plate detector.
Funding for research in Greece comes from competitive grants from the European Community and the Greek Ministry of Development (General Secretariat for Research & Technology). The Greek SMB groups are current users of European Synchrotron Sources (i.e. DESY/Hamburg, Elettra/Trieste) at the most once per year per group. Therefore all the above Greek research groups are very much interested in a facility like SESAME that would provide them with an additional synchrotron source and hopefully with a more immediate access.
3.2 Morocco - Abdelaziz Soukri Hassan II University, Casablanca
In Morocco basic molecular biology research and University programs are available. In the last five years we received encouragement for scientific research from the Moroccan government by financing each year several research programs (PROTAS project) in fields such as biology environment, medicine, biotechnology. SMB research is now starting with a few groups. Many universities and institutes are becoming aware of the importance of SMB research. On November 17, 2000 a meeting was organized for Moroccan scientists about the SESAME project. The meeting was prepared by me and Prof. Hommada, the Moroccan member of the SESAME Interim Council. A representative from the Ministry of Education and Research was present. Prof. Hoummada gave a presentation of the Sesame program and I give a talk about the importance of SMB research. Two important objectives were raised at this meeting: The first is the creation of an SMB network to include all scientists interested in SMB research at SESAME. This SMB network will be connected with Materials Sciences, a second network, and both connected with the RUPHE (Réseaux Universitaire du Physique des Hautes Energies) network. The second was planning of a project on protein engineering and molecular modeling involving two universities and one institute. The main objectives of this project are:
A. Understanding the mechanism of enzyme action stability and gene structure using directed mutagenesis and molecular modeling.
B. Study of conformational change during the regulation process
C. Study of the interaction of enzymes and metals
D. looking for a new and strong inhibitor of enzyme activity.
In all of these studies crystallization is very necessary in order to have information about the spatial structure. No crystallization facility exists in Morocco. It is expected that this will be provided at the SESAME site. We are starting a collaboration with the group of Prof. Sussman (Weizmann Institute) on protein crystallization. This collaboration was the result my participation at the annual meeting of the Israeli Crystallography Association in Jerusalem on June 1, 2000. Finally I can announce that the Moroccan government has signed the convention as a member country in the SESAME project and will provide a financial contribution.
3.3 Palestinian Authority - Said Assaf Arafat National Scientific Center for Applied Research
Palestine has eleven universities varying in number between 3,000 and 14,000 students. Four have M.S. graduate programs in chemistry and physics while three have medical colleges and health science education programs. In these faculties there are about seventy with Ph.D.’s in biological sciences and another approximately one hundred in various life science programs. However, there is little research at the Palestinian universities beyond M.S. thesis work and the extension of the Ph.D. research of individual faculty members. Some EU supported research is carried out on water utilization, environment protection, desalination, medicinal plants and their pharmacological effects, draught resistance of plants (such as jojoba and olives) and the isolation and quality control of their oils as high quality natural renewable oil products.
3.3.1 A particular research program in the Palestinian Authority; Nael Hasan Birzeit University
CELL ADHESION MOLECULES AND SMB
Cell surface adhesion molecules play a major role in cell signaling leading to growth and proliferation as well as tumor progression and metastasis. It has been reported that tumor cells treated with ionizing radiation (Onoda et al , Rad. Res. 1992) or with other cellular stress agents such as hypoxia (Young et al , Proc Natl Acad Sci, 1988) show an enhanced ability to form metastatic lung modules in recipient mice.
It has also been shown (Hasan et al, BJC 1998) that hypoxia caused a significant down regulation of the integrin family of cell adhesion molecules on human tumor cells and an associated decrease in cell adhesion which leads to cell detachment. Reoxygenation of these cells leads to reattachment by a process which is similar to migration and the formation of new metastases in vivo. It is well establishes that solid tumors have a hypoxic region in the center of tumors which is not responsive to radiotherapy and other drugs.
Loss of adhesion to extracellular matrices can be caused by either changes in regulation of expression or functional changes caused by conformational modifications in the structure of integrin subunits hence affecting the activity of cell adhesion molecules.
It is proposed that we study the conformational changes in integrins and other cell adhesion molecules in order to understand processes of cell migration, progression and invasion to form new metastases at distant sites, which helps in developing new approaches to cancer treatments. Antibodies are available to most integrins and cell adhesion molecules which would help in the purification procedure to prepare samples for synchrotron radiation.